Bartonella spp. in rodents and ectoparasites from Nigeria were carried out.Bartonellae are fastidious bacteria causing persistent bacteremia in humans and a wide variety of animals. In recent years there is an increasing interest in mammalian bartonelloses in general and in rodent bartonelloses in particular. To date, no studies investigating the presence of Bartonella spp. in commensal rodents and their ectoparasites in Nigeria. We report, for the first time, the molecular detection of Bartonella in 26% (46/177) of commensal rodents  and 28% (9/32) of ectoparasite pools  from Nigeria. Sequence analysis of the citrate synthase gene (gltA) revealed diversity of Bartonella spp. and genotypes in Nigerian rodents and their ectoparasites. Bartonella spp. identical or closely related to Bartonella elizabethae, Bartonella tribocorum and Bartonella grahamii were detected.The aim of the current study was to investigate the presence of Bartonella spp. was detected in commensal rodents and ectoparasites from Nigeria. The Bartonella spp. identified were previously associated with human diseases highlighting their importance to public health. Further studies need to be conducted to determine whether the identified Bartonella species could be responsible for human cases of febrile illness in Nigeria.High prevalence of infection with  Bartonella species are zoonotic vector-borne bacteria that typically parasitize the erythrocytes of mammalian hosts, resulting in long lasting infections. They are responsible for a wide range of clinical manifestations in both immunocompetent and immunocompromised hosts.Rodents and a wide range of small mammals serve as reservoirs of bartonellae, usually with no apparent clinical manifestations. Close association between rodents and humans especially in rural communities as well as in the overcrowded cities facilitates transmission of these bacteria.Bartonella spp. in rodents and ectoparasites from Nigeria. The aim of the current study was to investigate the presence of Bartonella spp. in commensal rodents and their ectoparasites in Nigeria and its public health implications. We report, for the first time, the molecular detection of Bartonella in 26% (46/177) of commensal rodents and 28% (9/32) of ectoparasite pools from Nigeria. Sequence analysis of the citrate synthase gene (gltA) revealed diversity of Bartonella spp. and genotypes in Nigerian commensal rodents and their ectoparasites. The Bartonella spp. detected in this study were identical or closely related to Bartonella elizabethae, Bartonella tribocorum and Bartonella grahamii previously associated with human diseases highlighting their importance to public health.There have been no studies investigating the presence of  Bartonella species have been affecting human life for centuries Bartonella species discovery, namely Bartonella bacilliformis, in 1905 by Alberto Leonardo Barton Thompson, more than 30 species of Bartonella were identified Bartonella species have been found in a variety of mammals, and the numbers of Bartonella species and their respective reservoir hosts are constantly growing Bartonellae are Gram-negative facultative intracellular alpha-proteobacteria belonging to the family Bartonellaceae. Many Bartonella are slow growers in vitro, and the most used diagnostic methods are isolation, serology and polymerase chain reaction (PCR). The use of sequencing on PCR amplicons has been recommended in order to detect new species, especially when dealing with uncommon clinical presentations and settings These bacterial species are transmitted between the reservoir and the final mammal host by hematophagous arthropods and insects such as fleas, sand flies, mites, lice and possibly ticks, usually by their bites Bartonella DNA has been detected in various hosts and possible vectors in many countries including, Israel Bartonella spp. in Nigeria.Bartonella spp. are difficult to diagnose and are seldom included in the differential diagnosis list in cases of FUO, specific Bartonella sp. treatment is rarely instituted to patients with FUO.Although there are no case estimates of fever of unknown origin (FUO) in Nigeria, the condition remains a challenging medical problem and unraveling the diagnosis could be a daunting task when investigating for common infective and non-infective causes. Moreover, since Bartonella spp., to investigate the presence of zoonotic Bartonella spp. in these rodents and ectoparasites and to evaluate genetic heterogeneity of circulating Bartonella strains in this country.The objectives of this study were to determine the possible infection of commensal rodents and their ectoparasites from Nigeria with The study protocol was read and approved by The National Veterinary Research Institute Vom Ethical Committee on Animal Use and Care. Permission to place the traps in the study area was granted by the residents. Animals were treated in a humane manner and in accordance with authorizations and guidelines for Ethical Conduct in the Care and Use of Nonhuman Animals in Research of the American Psychological Association (APA) for use by scientists working with nonhuman animals  in 2010.Rattus rattus, 121 Rattus norvegicus, 6 Mus musculus and 2 Cricetomys gambianus) were captured. Trapping was done using wire cage traps baited with smoked fish and other food scraps set out in the evenings when rodents are known to leave their holes to scavenge in farmlands or nearby human habitations. Traps were checked for rodents early the next morning. Cages containing rodents were transported to the Parasitology Laboratory, National Veterinary Research Institute (NVRI) Vom Nigeria, where they were identified and classified by a zoologist. At the laboratory, the cages containing rodents were placed into a clear plastic bag, which was sealed at the opening. Halothane gas was applied into the bag and the activity of the rodents was monitored. Once the rodents were anaesthetized, they were removed from the cage and bled by cardiac puncture. Depending on the size, 0.5–3 ml of blood was drawn and aliquoted into an EDTA tube and labeled. Each rodent was checked for ectoparasites by brushing the fur with a tooth brush onto a white cardboard paper. Ectoparasites were placed in labeled vials containing absolute ethanol corresponding to the host from which they were removed and stored at −20°C. Both blood and ectoparasite samples were transported in a cool box to The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Israel for analysis. The ectoparasites were morphologically identified by an entomologist (KYM) at the Department of Microbiology and Molecular Genetics in Jerusalem, Israel.Rodents were live trapped in domestic and peri- domestic areas in Vom (9°44′N/8°47′E) Nigeria between October–December 2011. A total of 177 rodents  according to manufacturer's instructions.DNA was extracted from blood using BiThe ectoparasites collected from each rodent species were pooled (2–3 arthropods per pool) according to genus and/or species. DNA was extracted from each pool using Illustra tissue and cell genomic Prep miniSpin kit  according to manufacturer's instructions.Bartonella sp. were aseptically scooped into microfuge tubes containing 50 µl of sterile Phosphate Buffered Saline (PBS). DNA was extracted from the bacterial colonies using Illustra tissue and cell genomic Prep miniSpin kit  according to the manufacturer's instructions.Pure cultured colonies of 5′ -GGGGACCAGCTCATGGTGG-3′) and reverse: BhCS1137.n (5′-AATGCAAAAAGAACAGTAAACA-3′) Bartonella citrate synthase gene (gltA). Positive and negative controls were included in each PCR run. PCR was performed using reaction tubes, preloaded with a premier PCR master mix . 50 µl total volume was used as follows: 3 µl of DNA template, 1 µl of 10 mM each primer, 1 µl MgCl2, 19 µl of ultra pure PCR water and 25 µl PCR master mix. Amplification was performed using a conventional thermocycler  and the following program parameters: an initial denaturing at 95°C for five minutes, and 35 cycles of denaturation at 95°C for one minute, annealing at 56°C for one minute, and elongation at 72°C for one minute. Amplification was completed by holding the reaction mixture at 72°C for 10 minutes.The oligonucleotide primers: forward BhCS871.p  and Analysis of DNA sequences and phylogenetic relationships were done using MEGA 5.Sequences were aligned by MUSCLE and the evolutionary history was inferred using the Maximum Likelihood method based on the Tamura-Nei model Rattus norvegicus rats; 26% (48/177) from Rattus rattus rats; 1.1% (2/177) from Cricetomys gambianus rats, and 3.4% (6/177) from Mus musculus mice.A total of 177 cardiac blood samples from four rodent species were examined in this study: 68.4% (121/177) from Rhipicephalus sanguineus (79) and Haemaphysalis leachi (6); 13 fleas, Xenopsylla cheopis (8), Ctenophthalmus spp. (5) and 62 Haemolaelaps spp. (gamasid mites) were recovered from the rodents. Ten additional Hemimerus talpoides (earwig sp.) were removed from the 2 C. gambianus captured  rodent blood samples screened in this study. One of 2 C. gambianus (50%), 36 of 121 R. norvegicus (29.8%), and 9 of 48 R. rattus (18.8%) were positive for Bartonella sp. DNA. None of the 6 M. musculus examined was positive for Bartonella sp. gltA. Nine of 32 (28%) ectoparasite pools removed from 48/177 (27.1%) rodents were positive for Bartonella gltA DNA. All the ectoparasite species tested were positive for Bartonella sp. gltA except H. leachi . Nine of the sequences obtained from R. norvegicus blood had 97–98% identity with GenBank deposited Bartonella tribocorum sequence, while 1 sequence had 98% similarity with GenBank deposited Bartonella grahamii. Nine sequences were obtained from R. rattus blood, 7 of which had sequence identity of 98–100% with GenBank deposited B. elizabethae sequence   . The seqBartonella gltA sequences obtained from one pool each of X. cheopis, R. sanguineus, and 3 pools of Haemolaelaps sp. had 97–100% similarity to B. elizabethae deposited in GenBank while a sequence from Ctenophthalmus sp. pool had 97% identity with B. tribocorum sequence deposited in GenBank. Interestingly, Bartonella sp. DNA with 99% sequence identity to B. elizabethae deposited in the GenBank was detected from one pool of H. talpoides earwigs that were removed from C. gambianus rats.Bartonella spp. DNA was detected in 4 of 13 (30.8%) rodents from which the ectoparasites were removed. However, only one ectoparasite, H. talpoides removed from C. gambianus had the same percent sequence identity (100%) with that of the host. The DNA sequences from the ectoparasites had 97–99% identity with their first GenBank match  Bartonella spp. DNA in the ectoparasites attests to their role as vectors of these bacteria.In this study, we report the molecular detection and genetic characterization of Bartonella spp. that were associated with human diseases were identified in this study, including B. elizabethae, B. grahamii and B. tribocorum. Bartonella elizabethae was found in patients with endocarditis Bartonella grahamii was associated with neuroretinitis or bilateral retinal artery branch occlusions Bartonella genotype closely related (97%) to B. tribocorum was detected in the blood of human patient with fever from Thailand Bartonella spp. in commensal rodents from Nigeria demonstrates their importance as reservoirs for various zoonotic Bartonella species and warrants increased awareness of physicians and health care workers for these pathogens especially in unidentified febrile cases.Several B. tribocorum was obtained from R. rattus rats. The detection of B. tribocorum only in R. norvegicus rats is in agreement with the earlier report of Márquez et al.Bartonella spp. for their rodent hosts In this study, no DNA sequence similar to R. sanguineus ticks in transmitting Bartonella spp. in nature is not proven Bartonella DNA in R. sanguineus ticks. Detection of Bartonella DNA in ticks was previously reported also by other authors Bartonella spp. DNA detected from one R. sanguineus tick pool had 97 percent identity to B. elizabethae sequences deposited in GenBank. It is worthy to note that the host from which the R. sanguineus ticks were removed was negative for Bartonella spp. DNA. This suggests that the ticks might have acquired the bacteria during previous feeding on an infected host. The ability of the tick to transmit this organism to a susceptible host during the next feeding stage or to its progeny is worth further investigation.Although the role of gltA sequences obtained from Bartonella spp. showed that commensal rodents in Nigeria harbor a diverse assemblage of Bartonella strains, some of which represent known Bartonella spp. and strains and others may represent distinct novel strains. Although only a portion of the citrate synthase gene (gltA) was used for phylogenetic analysis, this gene has been shown to be a reliable tool for distinguishing between closely related Bartonella genotypes Bartonella genotypes isolated from rodents with homologous sequences of Bartonella strains found in other mammals, reported from other parts of the world. Finding considerable sequence diversity is typical for different species of Bartonella, although more characteristics are needed to describe novel Bartonella species Comparative analyses of the Bartonella genogroups identified in commensal rodents formed three separate clusters closely related to B. elizabethae but distantly related to other known Bartonella spp. Although BLAST searches shows some of the sequences had 97–100% similarity to B. tribocorum and B. grahamii sequences deposited in GenBank  are presumed to feed on the epidermis of their host or as a saprophytic on fungus from the skin of the host. The detection of Bartonella sp. DNA in this ectoparasite is interesting and requires further investigation Pools of Bartonella genotypes in commensal rodents and ectoparasites from Nigeria, West Africa. A high prevalence and diversity of Bartonella spp. and strains was detected in commensal rodents and their ectoparasites in this study. Several zoonotic Bartonella spp. including B. elizabethae, B. grahamii and B. tribocorum were identified for the first time in Nigeria highlighting their importance for public health in this country.In conclusion, this study has resulted in the identification and genetic characterization of


Attention Deficit/Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder that has not been well studied in older adults. In this study we examined relationships between ADHD symptoms and cognitive ability and compared them between middle-age  and older-age  adults sampled from the same population. ADHD, mood disorder symptoms and cognitive abilities were assessed in a large population-based sample . We measured current ADHD symptoms using the adult ADHD Self-Report Scale (ASRS), which we found to have the same underlying structure in both cohorts. Older adults reported significantly lower levels of ADHD symptoms and 2.2% of the OA cohort scored equal or above the ASRS cut-off score of 14 (which has been previously associated with ADHD diagnosis) compared with 6.2% of MA adults. Symptom levels were not significantly different between males and females. Using multi-group structural equation modelling we compared ADHD symptom–cognitive performance relationships between the two age groups. Generally higher ADHD symptoms were associated with poorer cognitive performance in the MA cohort. However, higher levels of inattention symptoms were associated with better verbal ability in both cohorts. Surprisingly, greater hyperactivity was associated with better task-switching abilities in older adults. In the OA cohort ADHD symptom–cognition relationships are indirect, mediated largely through the strong association between depression symptoms and cognition. Our results suggest that ADHD symptoms decrease with age and that their relationships with co-occurring mood disorders and cognitive performance also change. Although symptoms of depression are lower in older adults, they are much stronger predictors of cognitive performance and likely mediate the effect of ADHD symptoms on cognition in this age group. These results highlight the need for age-appropriate diagnosis and treatment of comorbid ADHD and mood disorders. Attention Deficit/Hyperactivity Disorder (ADHD) is a neuropsychiatric disorder that develops in childhood and can persist throughout life. It is characterised by age-inappropriate levels of inattention and/or excessive motor activity and impulsivity th ed; DSM-5; ADHD is a common disorder affecting ∼5% of children and 1–7% of adults Although ADHD remains a categorically distinct clinical condition, there is increasing recognition that clinical ADHD lies at the extreme ends of the distribution of continuous ADHD symptom dimensions. Furthermore, symptoms of ADHD are common and can lead to functional impairment in adults who do not meet all the criteria for clinical diagnosis Cognitive deficits have been consistently identified in both children and adults with ADHD In this study we extend our analyses of ADHD symptoms to a cohort of older adults (68–72 years) in the Personality and Total Health (PATH) Through Life Study, a population-based longitudinal study of mental health and ageing The study sample was drawn from the PATH Through Life Project, a large longitudinal study of mental health and ageing in participants across three age groups  with a four-yearly follow-up ‘waves’ of assessment for up to 20 years p>0.05) from responders with respect to gender, total years of education and the levels of anxiety or depression symptoms in either cohort. Participants meeting at least one of the following criteria – history of epilepsy, brain tumour/infection and stroke and with missing data were excluded. Mini Mental State Examination (MMSE) was included in the assessment of the OA cohort to screen for probable dementia. Participants with scores of 23 or less (which is indicative of probable dementia The present study used data from the third wave of assessment (the ASRS was introduced in this wave) of the MA (40–44 years at baseline) and OA (60–64 years at baseline) cohorts. There were 2182 participants in MA cohort aged 48–52 years (mean age 50.7±1.5 years) and 1973 individuals in the OA cohort aged 68–72 years (mean age 70.6±1.5 years). Twenty-six (1%) and fifty-three participants (2.8%) in the MA and OA cohorts respectively did not complete the ASRS questionnaire and were excluded from further analysis. Being older was associated with increased odds of not completing the questionnaire in the OA cohort. However, non-responders did not differ significantly . Variables for panic disorder and other anxiety syndromes were combined to generate a binary categorical variable for anxiety symptoms .Depression and anxiety symptoms were assessed using the Patient Health Questionnaire (PHQ). This is a short version of the patient questionnaire component of the Primary Care Evaluation of Mental Disorders (PRIME-MD) instrument Cognitive data were collected from participants as described previously All statistical analyses were conducted using SPSS 18 and Amos version 20 (Chicago: SPSS Inc.). Missing data for cognitive measures were imputed using Expectation-Maximization method in SPSS. Means and standard deviations were computed for the ASRS-6 and cognitive test scores. As recommended We used multi-group structural equation modelling to test cross-group invariance of the ASRS factor structure (Aim 1) and compare ADHD symptom–cognition relationships in MA and OA groups (Aim 2). First, cross-group invariance of the ASRS factor structure was tested using latent factor SEM in the framework of confirmatory factor analysis Inatt ; Model 5b – FL, FC and variance of Hyperact (VHyperact); and Model 6: FL, FC and residual variance (RV) of the ASRS items. Since the more constrained models were nested within the initial model, the Likelihood Ratio Test (difference in Chi-square statistics relative to the change in degrees of freedom) along with other goodness-of-fit indices (see above) was used to select the more parsimonious model.Analysis of ASRS factor structure: Previous factor analysis has established that ASRS measures two correlated constructs, Inattention and Hyperactivity Inatt, Hyperact, sociodemographic variables and mood-disorder symptoms as predictors. A schematic representation of our theoretical model is shown in Inatt and Hyperact and covariance between the factors were constrained to be equal across both groups. All other parameters were estimated freely. To avoid multi-collinearity we used separate models for cognitive variables  that were highly correlated  removed to improve the overall parsimony of the models. Only the final, most-parsimonious model and the coefficients of significant paths are reported. Results were considered significant at p≤0.05.Analysis of ADHD symptom–cognition relationships: SEMs generated for assessing the effect of ASRS latent factors on cognitive performance included cognitive test scores as dependent variables and We also analysed the factor structure of the cognitive tests used in the study. The factor structure that represents the best fit to both cohorts are shown in http://crahw.anu.edu.au/research/projects/personality-total-health-path-through-life/data). The OA cohort reported significantly lower levels for ADHD, depression and anxiety. For the ASRS, 2.2% of participants in the OA cohort scored 14 or above, which has previously been identified as indicative of ADHD diagnosis Demographic characteristics, symptom measures for ADHD, depression and anxiety, and cognitive test scores for both cohorts are presented in Inatt+Hyperact) ASRS structure in both cohorts individually . Significant paths (p≤0.01) in the final model are shown in Using multi-group SEMs we investigated the effects of ADHD symptoms on cognitive performance, while controlling for sociodemographic variables and mood disorder symptoms . The ASRInatt and Hyperact have limited direct effects on cognitive performance. The most notable was a positive association, observed in both cohorts, between Inatt and Spot-the-Word Test, implying that higher levels of inattention symptoms are associated with greater verbal intelligence. Inatt was also positively associated with Choice Reaction Time, i.e., with slower reaction time in the MA cohort. Hyperact was positively associated with the Delayed Recall test (i.e. poor performance) on the MA cohort and Trail Making Test (Part B) (i.e. better performance) in the OA cohort. Inatt was associated with depression and anxiety symptoms more strongly in the MA than the OA cohort.We also investigated the association between ADHD symptoms and latent variables obtained from factor analysis of the cognitive test scores. Factor analysis identified four latent factors  broadly Inatt only in the MA cohort. It had an effect on the Trail Making Test (Part A) in the OA cohort and had no effect on any of the cognitive variables in the MA cohort. Effects of age on the cognitive variables were similar across both cohorts although the effects were stronger in the OA cohort. A point of contrast was the significant effect of age on Delayed Recall test on OA cohort that was absent in the MA cohort. Age was marginally associated with Hyperact in older adults only. Education had negative effects on mood variables in both cohorts although the effect on anxiety was much stronger in the OA cohort. The effect of education on Inatt was positive in both cohorts and comparatively stronger in the MA cohort, implying that more education is associated with higher levels of inattention. Greater levels of depression symptoms were associated with poorer cognitive performance generally, but the effect is much stronger in the OA cohort. These results did not differ significantly when latent factors underlying the cognition tests were included as dependent variables in the SEM models  older adults reported fewer/less severe ADHD symptoms compared to middle-aged adults; ii) the effect of ADHD symptoms on cognitive performance was weaker in older adults compared to middle-aged adults; iii) in OA adults the ADHD symptom–cognition relationship was mostly indirect and mediated through the strong association between depression symptoms and cognition.We found that 2.2% of the OA cohort met the suggested cut-off for the ASRS-6 score that has been linked to clinical diagnosis in previous studies. This estimate falls within the range of 1–2.5% ADHD prevalence reported in the literature for older adults There may be several reasons for this apparent decline in ADHD symptom levels in old age. The effects of ADHD may become less discernable from other general age-related changes. Thus, even though, as we have demonstrated here, the ASRS appears to measure variation in the same psychological construct in old age, it may do so with lower sensitivity. The relative frequency of people with ADHD in the population will also tend to decline in old age because they have a relatively lower life expectancy We did not find any significant gender difference in ADHD symptoms in older adults. This result is consistent with our previous observation Inatt and Hyperact were more strongly correlated in MA than OA adults, however, this difference was not statistically significant. In a previous study of two samples of different age We replicated the factor structure of the ASRS reported by Hesse et al. (2013) Inatt, in contrast with the MA cohort, suggesting that information processing speed is less affected by symptoms of inattention in older adults.In both MA and OA cohorts the Spot-the-Word Test, which measures verbal ability, was positively associated with symptoms of inattention, an effect that we previously reported for the MA cohort p<0.01. This might suggest that hyperactivity symptoms in this age-group are beneficial for certain cognitive activities. It is possible that hyperactivity symptoms in ageing brains make the system noisier at the neuronal level. While noise is generally considered detrimental, under certain circumstances it may aid in processing of weak stimuli through the phenomenon of stochastic resonance Surprisingly, in the OA cohort, greater hyperactivity was associated with better task-switching abilities as measured by the Trail Making Test (Part B). However, this association did not reach the more stringent significance threshold of Our results suggest that the effects of ADHD symptoms are specific to particular cognitive domains, in contrast to a previous study by Biederman et al (2011) Inatt was strongly associated with depression symptoms in both cohorts, and depression symptoms predict worse performance in all cognitive tests in the OA cohort but not in the MA cohort. We also found evidence of statistical mediation of Inatt on Symbol-Digit Modalities Test by depression in OA adults since the negative association between Inatt and Symbol-Digit Modalities Test became non-significant when depression symptoms were included in the model. Depression symptoms were also significantly associated with Symbol-Digit Modalities Test in OA adults. Thus, our results emphasise the importance of controlling for comorbid mood disorders when investigating ADHD symptom–cognition relationship, especially in older adults.Our results suggest that inattention symptoms affect cognitive performance indirectly through their effect on depression in the OA cohort. The strengths of this study are that it was conducted in a large representative population sample, and hence it is likely to be free of the biases that can be associated with clinical and convenience samples. Furthermore, the narrow age range of the sample removes the possible confounding effects of age within each cohort. Consequently, our results are likely to be generalisable to MA and OA populations. Our study included age groups that have not been well studied with respect to ADHD symptoms and thus is a significant addition to the growing literature in this area. We focus on cognitive performance and ADHD symptoms highlighting differences between middle- and old-age, which is important for understanding age-related cognitive change. Finally, we have modelled both direct ADHD symptom-cognition relationships and indirect effects mediated by symptoms of depression, demonstrating age-group differences in these direct and indirect pathways.Limitations of the study include lack of clinical assessments for ADHD, depression and anxiety. In addition, symptom measures are based on self-reports, which may not be completely accurate  and OA (B) cohorts. Standardised factor loadings are shown. IR: Immediate Recall; DR: Delayed Recall; SRT: Simple Reaction Time; CRT: Choice Reaction Time; TMT-A: Trail Making Test A; TMT-B: Trail Making Test B; SDMT: Symbol-Digit Modalities Test; STW: Spot The Word test; DSB: Digit Span Backwards.(TIF)Click here for additional data file.Figure S2p<0.05 are shown. Arrows reflect direction of relationships between variables. Standardised regression coefficients are shown. gen: gender; educ: education; Inatt: latent factor Inattention; Hyperact: latent factor Hyperactivity; DEP: depression symptom measure; ANX: anxiety symptom measure. Indicators of the latent variables are not shown for the sake of clarity.Final model for ADHD symptom–cognition analyses for MA (A) and OA (B) cohorts. Only paths significant at (TIF)Click here for additional data file.File S1Tables S1–S5.(DOCX)Click here for additional data file.


Background. This cross-sectional study evaluated rate of reported ADHD symptoms among male preschoolers in Ahvaz by different informants and rate of their agreement. Method. One hundred ninety-two 5-6-year old boys from nine kindergartens in Ahvaz were selected. Teacher and parents' Conners ADHD rating scales were used. Findings. For 133 children, questionnaires were returned. Prevalence of children with positive questionnaire was 24.06%, with only parent questionnaire was 4.51%, with only teacher questionnaire was 17.29%, and with both informants was 2.25%. Teacher-parent agreement was low (P = 0.0001). Conclusions. ADHD symptoms are frequently reported by informants and may be more reported by teachers than parents and teacher-parent agreement may be low. Interview with different informants and observation of child behavior are needed for documentation of diagnosis. Attention Deficit Hyperactivity Disorder is a developmental disorder with persistent pattern of distractibility, hyperactivity, restlessness, and other disturbances of executive function , 2. It iThis study was a part of the other study that we carried out to evaluate growth parameters of ADHD children and institutional review board of Ahvaz Jundishapur University of Medical Sciences (AJUMS) approved it. This descriptive cross-sectional study determined prevalence of ADHD symptoms in male preschool-aged children in kindergartens (preschoolers had been admitted by both school and kindergarten in Ahvaz during our study) of Ahvaz  city in Iran and estimated rate of agreement between parents and teachers. Nine kindergartens were selected from different areas of Ahvaz by cluster sampling in 2010. One hundred ninety-two 5-6-year old boys were selected. Boys were selected because of the higher prevalence of ADHD in male , 4 and bP = 0.0001).For 133 children questionnaires were returned, but for other children questionnaires were not returned. Prevalence and incidence of children with and without positive Conners rating scale by different informants were determined . Of 32 cIn our study the prevalence of reported ADHD symptoms among male preschoolers in Ahvaz by informants was 24.6% among 5-6 year-old boys in kindergartens in Ahvaz. This prevalence rate is higher than in previous studies. The prevalence of ADHD in Mashhad city, in northeast of Iran, in male preschoolers was 18.1% . These s The prevalence of ADHD in studies is different depending on the diagnostic criteria and tools used for evaluation of ADHD , 4. The On the other hand, there is some controversy in the literature whether ADHD is a biological disorder or cultural disorder. A review study suggested that cultural differences are one of the factors that in studies affect the prevalence of ADHD . BecauseIn our study most of the children with positive rating scales had been only reported by teachers and a fewer number of them had been only reported by parents or by both parents and teachers. This result suggests that ADHD symptoms may be more reported by teachers than parents and teacher-parent agreement may be low. Other literature also reported that there is a variation in prevalence of ADHD depending on different informants , 4. For Informant disagreement may be due to several factors: different contexts of the observation, informant psychopathology, situation, kind of activity, informant attitude, and their characteristics. Children with ADHD may differently act in each setting. They are more hyperactive in unstructured situation. Conversely, problems in attention are most often seen in classroom setting and carrying out tasks. So rule-enforced activity may be a differentiating factor.Children with ADHD have better function in one-to-one versus group situation. Also, they may better interact with animal and younger or older person than themselves, because of unconditional love in these relationships , 22, 25.One limitation of this study was lack of cooperativeness of some parents and teachers that did not refer questionnaires. Besides, severe ADHD children were not available.In conclusion, our study suggested that ADHD symptoms are frequently reported by teachers and parents by means of screening questionnaire. Although some false positive may exist in our results, nonetheless, high score in Connors rating scale represents complaint and difficulties of teachers and parents that must be addressed. Participation of parents and teachers of children with positive screening test in interview session and observation of child behavior are needed for documentation of diagnosis.


Bartonella spp., we estimated Bartonella spp. prevalence and genetic diversity in bats in Guatemala during 2009. We found prevalence of 33% and identified 21 genetic variants of 13 phylogroups. Vampire bat–associated Bartonella spp. may cause undiagnosed illnesses in humans.To better understand the role of bats as reservoirs of  Multiple studies have indicated that bats might serve as natural reservoirs to a variety of pathogens, including rabies virus and related lyssaviruses, Nipah and Hendra viruses, Marburg virus, and others ; the other 14 species accounted for 0.8%–12.7% of the bats sampled. Diversity of bats was 6–8 species per site  of the 118 bats; colonies with different morphologic characteristics were identified from blood of 2 Pteronotus davyi bats. Prevalence of Bartonella spp. in Conguaco  was significantly higher than that in Oratorio , San Lucas Tolimán , and Taxisco  but did not differ from that in Santa Lucía Cotzumalguapa . Bartonella spp. were cultured from 8 bat species. The Bartonella spp. prevalence among Phyllostomus discolor , P. davyi , and D. rotundus  bats was significantly higher than that among Sturnira lilium  and Glossophaga soricina  bats. No Bartonella spp. were found in Artibeus jamaicensis (0/13) and 6 other bat species tested  and BhCS1137.n (5′-AATGCAAAAAGAACAGTAAACA-3′). Subsequent sequencing analyses of the 41 isolates revealed 21 genetic variants  prevalence of Bartonella strains representing a variety of distinct phylogroups represent novel Bartonella species. Unlike the discovery in bats in Kenya  may have made them major reservoirs that contribute to the maintenance and transmission of Bartonella spp. are being associated with human illness, the need to identify the animal reservoirs of these novel Bartonella spp. and to understand their disease ecology is also increasing. Our study of Bartonella spp. in bats has enlarged our scope of this zoonotic potential as we search for the reservoirs that harbor novel and known Bartonella spp.Because an increasing number of


Background: Cocaine-dependent individuals (CDI) present executive cognitive function (ECF) deficits, but the impact of psychiatric comorbidities such as Attention-Deficit Hyperactivity Disorder (ADHD) on neuropsychological functioning is still poorly understood. The aim of this study was to investigate if CDI with ADHD (CDI + ADHD) would have a distinct pattern of executive functioning when compared with CDI without ADHD (CDI).Methods: We evaluated 101 adults, including 69 cocaine-dependent subjects (divided in CDI and CDI + ADHD) and 32 controls. ECF domains were assessed with Digits Forward (DF), Digits Backward (DB), Stroop Color Word Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Frontal Assessment Battery (FAB). DSM-IV criteria for ADHD were used for diagnosis and previous ADHD symptoms (in the childhood) were retrospectively assessed by the Wender-Utah Rating Scale (WURS).Results: There were no significant differences between CDI + ADHD, CDI, and controls in estimated intellectual quotient (IQ), socioeconomic background, education (in years), and pre-morbid IQ (p > 0.05). SCWT and WCST scores did not differ across groups (p > 0.05). Nevertheless, CDI and CDI + ADHD performed more poorly than controls in total score of the FAB (p < 0.05). Also, CDI + ADHD did worse than CDI on DF , DB , Conceptualization/FAB , and Mental flexibility/FAB . We did not find correlations between cocaine-use variables and neuropsychological functioning, but previous ADHD symptoms assessed by WURS were negatively associated with DF (p = 0.016) and with the total score of the FAB (p = 0.017).Conclusion: CDI + ADHD presented more pronounced executive alterations than CDI and CDI exhibited poorer cognitive functioning than controls. Pre-existing ADHD symptoms may have a significant negative impact on executive dysfunction in CDI. It remains to be investigated by future studies if symptoms such as impulsivity or a pre-existing ECF dysfunction could represent underlying cognitive endophenotypes that would substantially increase the risk for acquiring addictive disorders. There is accumulating evidence from cognitive neuroscience research that cocaine-dependent individuals (CDI) present prefrontal cortex (PFC) functional and structural abnormalities –5, whichOur research group has shown that cocaine-use is associated with hypoperfusion in several areas of the brain  and thatper se leads to ECF alterations through its influence on brain functioning, or if the ECF deficits would represent pre-morbid factors which may lead to stimulant dependence  met the DSM-IV-TR criteria , two urine tests were used to verify recent cocaine-use (if positive) and after to verify their abstinence (if negative), since recent cocaine-use may mask cognitive impairments in CDI (n = 2) and the local police department (n = 12). We also recruited adult students from a public school (n = 18). The transport costs of the volunteers were reimbursed. The exclusion criteria for the control group were: (1) met DSM criteria for any psychoactive substance dependence other than nicotine; (2) the same exclusion criteria of the cocaine group.Hundred and one subjects participated in this study. All the CDI . After signing an informed consent, participants were interviewed by either a clinical psychologist or a psychiatrist. The interview questions covered demographics, drug use, and the consequences of drug use on their psychosocial functioning. Investigators obtained initial demographic and clinical information by a semi-structured interview used by neuropsychologists at our research center . The semAddiction Severity Index   and the ty Index .Digits forward was used was used to measure attention span and DB working memory . In DF tIt was designed to measure selective attention, cognitive flexibility, and inhibitory control , 46. HerThe 64 card version , 48, traThe administration of the FAB takes approximately 10 min; each subtest is scored from 0 (minimum score) to 3 (maximum score) and the total score of the FAB is the sum of the scores in the six subtests  . The FABWe used short forms of the Wechsler Intelligence Scale for Adults – Revised  and theIt evaluates retrospectively different symptoms of ADHD. Here we used an abbreviated version of the Wender-Utah Rating Scale (WURS) comprising 25 of the 61 items from the original scale, which has shown to better discriminate between patients with ADHD and a non-patient comparison group . ParticiIt is based in nine symptoms of Inattention and nine symptoms of Hyperactivity/Impulsivity . The patWe only considered subjects in the group called CDI + ADHD if they had fulfilled both confirmation of the adult ADHD diagnosis by DSM-IV-TR criteria  and if tt-tests and categorical variables were evaluated using Fisher’s exact test. The normal distribution of each cognitive variable was confirmed by the Kolmogorov–Smirnov test. The level of statistical significance was α = 0.05 and all statistical tests were two tailed. Comparative analysis considering three groups  was made using Analysis of Variance (ANOVA) and Bonferroni post hoc testing. Additionally, between-group analysis of cognitive functioning was conducted using Analysis of Covariance (ANCOVA) with age and gender as covariates. Correlation between neuropsychological measures , cocaine-use variables , and WURS  was assessed by the Spearman correlation coefficient (rs). All statistical analyses were conducted using Statistical Package for the Social Science (SPSS) software version 14.0 for Windows.Differences in performance on neuropsychological tests were assessed with unpaired Socio-demographic and some clinical characteristics of the groups are described in Table n = 11) and CDI (n = 58). CDI + ADHD had significantly higher WURS scores, followed by CDI and normal controls , socioeconomic level, estimated IQ, and vocabulary score. However we found differences among groups regarding age, gender, ethnicity, handedness, and childhood ADHD scores (WURS). Controls were younger, male, more frequently white, and left-handed, in comparison to both CDI + ADHD n = 1 and CDIGroups with a history of cocaine dependence (CDI and CDI + ADHD) did not differ significantly in terms of the main cocaine-use variables, such as age at onset, duration (in years), and length of abstinence Table . They alF = 4.756, p = 0.011) and in working memory  tasks (Table Post hoc comparisons showed that the difference in DF was due to worse performance of CDI + ADHD in comparison to both CDI (p = 0.013) and controls (p = 0.011). CDI did not differ significantly from controls in this task (DF). Differences in the test of working memory (DB) were due to a lowered performance of both groups of cocaine-dependents (CDI + ADHD and CDI) when directly and separately compared with controls .The ANOVA including the three groups  did not show any statistically significant difference among patients and controls in all measures of SCWT and WCST. However, groups differed in attention , FAB’s Mental flexibility  and in the total score of the FAB . Post hoc analyses showed that the significant difference in Conceptualization was due to a worse performance of CDI + ADHD when directly compared with the normal controls (p = 0.010). Difference detected in Mental Flexibility by ANOVA was associated with a lowered performance of CDI compared to controls .We also found statistically significant differences in FAB’s Conceptualization , length of abstinence from cocaine (in days), and WURS total scores.rs = −0.286; p = 0.016) and WURS with the FAB total score . Correlations were analyzed considering both groups of patients together (CDI and CDI + ADHD) (Table Variables regarding cocaine-use were not correlated with executive functioning in this study. We found a significant negative association between childhood ADHD symptoms as measured by WURS and DF (D) Table .p < 0.05).Additionally, considering the differences between samples, between-group analysis of cognitive functioning was conducted using Analysis of Covariance (ANCOVA) with age and gender as covariates, and the results described above remained significant , which may negatively impact the normal development of the PFC, which in turn leads to poor decision-making, which heightens the risk for acquiring addictive disorders . The litper se is associated to neuropsychological deficits affecting predominantly ECF, ADHD-related symptoms may be an explaining suggestive factor for the future development of cocaine dependence. Much more than a “confounding factor,” ADHD might be an “explaining factor” for the understanding of possible cognitive endophenotypes associated with cocaine dependence. It is possible that CDI + ADHD would represent a subgroup of patients whose cocaine-use may be associated with a certain type of “self-treatment” for pre-existing ADHD symptoms (p = 0.005), to which similar pharmacological and behavioral strategies used for ADHD could be beneficial. For example, a recent study showed that oral methylphenidate  may induce better performance (reducing errors) on the SCWT leading to a more careful responding by reducing brain activity in the dorsolateral PFC of CDI as measured by fMRI  as well as their genetic and neuroimaging underpinnings.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Rye is one of the most important crops in Eastern and Northern Europe. Despite the numerous beneficial features of rye, its annual production decreases successively which correlates with the lack of progress in its breeding compared with other cereals. Biotechnological methods could effectively improve the breeding of rye. However, their application is highly limited by the absence of an efficient procedure for plant regeneration in vitro, since rye is one of the most recalcitrant cereals with regard to the tissue culture response (TCR), and successful regeneration is highly dependent on genotype. Efforts to understand the genetic mechanisms controlling TCR of rye have elucidated some basic aspects, and several genes and genome regions controlling this trait have been identified. The aim of this review is to summarize the limited current knowledge of this topic. Secale cereale L.) is one of the most important cereals cultivated in Eastern and Northern Europe. The crop possesses a great number of advantages such as a unique nutritional value, winter hardiness and tolerance to environmental stresses as low temperatures, drought and poor soil conditions. Recently, nevertheless, a distinct reduction of cultivation area and yield of rye has been observed compared to other cereals. This is mainly caused by a relatively slow breeding progress connected, predominantly, with a high self-incompatibility and inbreeding depression. At present, the main task of rye breeding is the improvement of resistance to diseases  and pre-harvest sprouting . Biotechnological methods, e.g., double haploid production, genetic transformation or selection of plants with beneficial somaclonal changes could effectively improve the breeding of rye. However, their application is limited by a lack of an efficient procedure of plant regeneration in vitro, as rye is one of the most recalcitrant cereals in regard to in vitro plant regeneration ability  have explored some basic aspects, and allowed the identification of several genes and genome regions controlling this trait  and abiotic (a broad range of culture conditions and interactions between them), have been tested to try to establish an optimal protocol for efficient and replicable in vitro regeneration of rye.S. africanum and S. kuprianovii , whereas the majority of those that show a response are “differentially responding” . Examples of “universally responding” forms are line L318, which is classified as a positively responding genotype, and line L9, which is a non-responding one  and sucrose (30 g/dm3) is the best induction medium for somatic tissues, whereas most efficient plant regeneration is promoted by MS  with IAA  or lacking PGR. On the other hand, Zimny and Lörz  that differ in their TCR showed that the in vitro response of immature embryos and immature inflorescences is controlled by a complex, polygenic system with various gene interactions, and that the plant regeneration ability is a recessive trait  were used for phenotypic evaluation. A QTL analysis based on four parameters describing the reaction of immature inflorescences and immature embryos resulted in the identification of nine putative QTLs controlling rye TCR  mapping population was developed from the cross L318 × L9. A total of 102 RILs (FSERK (Somatic Embryogenesis Receptor-Like Kinase), LEC1 (Leafy Cotyledon 1) and NiR (Nitrate Reductase), plus Vp1 (Viviparous 1), a gene not previously investigated with respect to TCR (Gruszczyńska and Rakoczy-Trojanowska SERK encodes a RLK (Receptor-Like Kinase) protein and it has been shown to play an important role during somatic embryogenesis induction in many plants, e.g., carrot Dactylis glomerata and Arabidopsis thaliana , LEC1 is necessary to maintain the embryogenicity of cells  to regulate the activation of genes taking part in embryo maturation, and (2) to inhibit the expression of genes coding for hydrolases in the course of cob development and maturation  and incapable (E < 25) of embryogenic callus formation. The application of this method generated 47 unique sequences for characterization , amino acid permease and acetyl-CoA carboxylase, respectively, which indicates that they may play some regulatory function in the transcription of these genes. The gene CBF10 together with its potential regulating factors are particularly interesting, since increased expression of CRT/DRE-related genes is usually associated with osmotic stress that is present under tissue culture conditions. Real-Time RT-PCR analysis of GDDSCDSs selected by bioinformatic analysis showed their diverse expression at different stages in the culture of tissues from the well responding inbred line L318 and the non-reactive line L9. The expression profiles of the majority of isolated sequences were in agreement with the subtraction direction, i.e., the transcript levels of R and E > 90 sequences were higher in line L318 than in line L9 . Nevertheless, some of the GDDSCDSs showed the opposite pattern of transcription, or their expression profiles were more complicated, being in agreement with the subtraction direction only at some culture stages. A similar phenomenon was observed in the case of SE-related rye orthologs: enhanced expression of the ScSERK, ScVP1, ScLEC1 and ScNiR transcripts in the positively responding line L318 was limited to the regeneration phase (Fig. The molecular mechanisms controlling rye TCR were further examined by the application of GDDSC, a method that permits the isolation of specific sequences from DNA bulks that differ with respect to the investigated trait and also generates markers tightly linked to this trait (Przybecki et al. able E < 5 of embrLEC1 and VP1 genes may interact in a complementary manner to perform the role of negative regulators of embryogenic callus development distinguished by Mendelian analyses. In addition, ScVP1 seems to suppress ScSERK, which positively regulates the initiation of processes leading to somatic embryogenesis (Gruszczyńska and Rakoczy-Trojanowska In general, the results of molecular studies have confirmed the conclusions drawn from Mendelian and cytogenetic analyses, and show that at least two processes in rye, namely callus production and plant regeneration, are recessive traits regulated in a complex manner. For example, orthologs of the The results of both cytogenetic and QTL analyses suggest that the factors influencing rye TCR are spread across multiple chromosomes: 1R, 3R, 5R 6R, 7R according to cytogenetic data (Lazar et al. R_285H8 and E > 90_330B8, as their expression level was found to be considerably higher in almost all tissue culture stages of the positively responding line L318. Conversely, markers based on the GDDSC product NR_340Bl8, and the ScVP1 and ScLEC1 genes may assist in the selection of negatively responding forms. The rapid development of molecular techniques such as NGS should significantly accelerate work in this field in the near future.Although knowledge about the genetic control of TCR in rye is still limited and rather fragmentary, and the use of tissue culture for breeding and genetic manipulation remains very difficult, the results of investigations conducted over the last decade have uncovered details of some of the mechanisms involved. Several genes and genome fragments that play an important role in the regulation of TCR have been discovered. Some of these may serve as the source of molecular markers for the selection of positive genotypes, particularly the GDDSC products


Attention Deficit/Hyperactivity Disorder (ADHD) is a pervasive neurodevelopmental disorder characterized by 3 clusters of age-inappropriate cardinal symptoms: inattention, hyperactivity and impulsivity. These clinical/behavioural symptoms are assumed to result from disturbances within brain systems supporting executive functions including working memory (WM), which refers to the ability to transiently store and flexibly manipulate task-relevant information. Ongoing or past medications, co-morbidity and differences in task performance are potential, independent confounds in assessing the integrity of cerebral patterns in ADHD. In the present study, we recorded WM-related cerebral activity during a memory updating N-back task using functional Magnetic Resonance Imaging (fMRI) in control children and never medicated, prepubescent children with ADHD but without comorbid symptoms. Despite similar updating performance than controls, children with ADHD exhibited decreased, below baseline WM-related activation levels in a widespread cortico-subcortical network encompassing bilateral occipital and inferior parietal areas, caudate nucleus, cerebellum and functionally connected brainstem nuclei. Distinctive functional connectivity patterns were also found in the ADHD in these regions, with a tighter coupling in the updating than in the control condition with a distributed WM-related cerebral network. Especially, cerebellum showed tighter coupling with activity in an area compatible with the brainstem red nucleus. These results in children with clinical core symptoms of ADHD but without comorbid affections and never treated with medication yield evidence for a core functional neuroanatomical network subtending WM-related processes in ADHD, which may participate to the pathophysiology and expression of clinical symptoms. Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common childhood developmental disorder characterized by three clusters of age-inappropriate cardinal symptoms: inattention, hyperactivity and impulsivity. Worldwide prevalence is high (around 5%) The neural patterns associated with WM in adults are well characterized, mostly involving a bilateral parieto-frontal network in the classical N-back task We addressed these issues using fMRI by investigating the cerebral activity subtending WM in prepubescent children presenting or not the clinical symptoms of ADHD, matched for behavioural performance, selected with stringent criteria excluding co-morbidity, and never treated with medication. Results evidence specific functional cerebral patterns subtending WM-related processes in the ADHD, which may underline the pathophysiology and the expression of clinical symptoms.t = 1.53, p = 0.13). All children were scanned using 3T fMRI in a block design during alternating practice between two conditions in the N-back task Behavioural and neuroimaging analyses were conducted on right-handed children fulfilling the DSM-IV criteria for the ADHD combined type (n = 19) and healthy volunteers (n = 14). Mean age was similar in ADHD (10.75±1.31 years) and Control (10.05±1.28 years) groups (pssvc <.05), and in the left calcarine gyrus pcorr <.05; svc <.05), an output nucleus of the cerebellum projecting onto frontal cognitive areas associated with WM processes In line with previous findings in healthy adults psunc <0.001), known to participate in WM processes. The reverse contrast was non significant, i.e. we failed to disclose any area in which activity was more correlated with calcarine activity in Control than ADHD children. The same analysis conducted with the right cerebellum as COI (20 −84 −26 mm) revealed a highly significant tighter coupling in ADHD than Controls with activity in an area compatible with the brainstem red nucleus . Data inspection revealed that correlation coefficients between the right cerebellum and the red nucleus area were positive but higher in ADHD than controls in the N2 condition (average r N2 = 0.18±0.04 vs. 0.1±0.15), and equally negative in the N0 condition (average r N0 = −0.07±0.17 vs. −0.09±0.16). Similar connectivity patterns with the right cerebellum were disclosed in the right amygdala, middle temporal gyrus and precuneus, left middle and frontal inferior gyri, right lingual gyrus and left cerebellum . Likewise, activity in the left inferior parietal COI (−54 −48 44 mm) was more tightly coupled in ADHD than Controls with activity in the bilateral inferior and middle frontal gyri, in the right superior temporal gyrus, in the left supplementary motor area (SMA) and anterior cingulate cortex (psunc <0.001), also involved in WM processing. Finally, right caudate nucleus COI (10 4 14 mm) activity was more tightly coupled in ADHD subjects than Controls with activity in right putamen, right insula lobe, right pallidum, bilateral middle frontal gyrus and the right superior frontal gyrus (psunc<0.001).Above specific activation/deactivation patterns in regional cerebral activity, we reasoned that ADHD children might establish distinctive functional neuroanatomical connectivity patterns during WM performance, allowing them to succeed to the task. To test this hypothesis, we computed psychophysiological interaction (PPI) In the present fMRI study, we investigated changes in regional cerebral activity and functional connectivity within brain networks underlying WM processes in children with ADHD. Importantly, our ADHD children population was carefully selected, naïve for any medication and devoid of the often-present co-morbidity, and behavioural performance was at the same level than in Controls, thus discarding the hypothesis that brain activity differences could be due to these confounding parameters. Possible limitations in the interpretation of our results are linked to the facts that having observing equal performance in the WM updating condition does not automatically imply that behavioural differences could not have been observed in more challenging conditions, and that cognitive resources needed to succeed to the task may already be differentially challenged in the two populations. Also, even if usually more robust, block-design fMRI approaches make that averaged cerebral activity over a block encompasses both the component of interest (i.e. the updating process in WM) and other less controlled cognitive processes differentiating performance on a target updating task (N-back 2) and on a control detection task (N0).Notwithstanding, our results indicate at first glance similar patterns of working memory (WM)-related cerebral activity in ADHD and Control children, also in line with previous findings in healthy adults Decreased WM-related activity in the left occipital region is partially reminiscent of previous findings in ADHD adults Inferior parietal cortex (IPC) activity remained close to baseline under WM condition in ADHD children, whereas it markedly increased in Controls. A lack of WM-related activation in the IPC in ADHD corroborates findings from prior fMRI studies conducted in children, adolescent and adult populations with ADHD WM-related changes in striatum activity have been previously reported in the ADHD Cerebellar activity at rest in adult ADHD participants was previously found increased in the vermis after methylphenidate administration normalizing behavioural symptoms, and associated with ADHD ratings in Crus II Additionally, our findings are the first to disclose tightened positive relationships under WM load in ADHD between cerebellar activity and BOLD signal changes in a brainstem area compatible with the red nucleus (RN). Available data suggest anatomical and functional relationships between the RN and a widespread sensorimotor, limbic and associative network that mainly plays a modulatory role in complex sensorimotor and cognitive processes such as WM Finally, our results failed to evidence any significant WM-related differences between ADHD and controls in prefrontal regions, although considered a critical neural substrate for WM in many studies Forty-two children aged 8–12 years and one of their parents gave their written informed consent to participate in this study approved by the Ethics Committee of the Erasme University Hospital, ULB, Bruxelles, Belgium. Out of 42 participants, 3 children with ADHD were excluded from the analyses following the discovery of anatomical brain abnormalities, 2 children with ADHD were excluded due to excessive head motion during MRI scanning, and 4 children  were excluded based on insufficient performance during the N-back task (>1.96 SD below mean group performance).t = 1.53,df = 31, p = 0.13). Population consistency was also ensured with respect to handedness, age range, diagnosis of combined-type and absence of co-morbidity. Children with ADHD were recruited from the Department of Neuropediatrics, outpatient clinic in Erasme Hospital, ULB University. Healthy children agreed to participate upon announcement or personal query. All participants were identically assessed by the same child psychiatrist (IM). Diagnosis for ADHD was based on clinical features including typical history and behavioural reports. The Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version  and 14 healthy volunteers (8 boys). Mean age was 10.75±1.31 years in ADHD and 10.05±1.28 years in control children . Thirty-two contiguous transverse slices were acquired, covering the whole brain. Anatomical images were obtained using a T1-weigthed sagittal 3D TFE sequence . The MR scanner was equipped with the Quasar imaging gradients (maximum amplitude and slew rate: 30 mT/m and 200 mT/m/ms) and a 8-channel SENSE head coil.Data were acquired on a Philips Achieva 3-T  scanner using a T2* sensitive gradient echo (EPI) sequence  software implemented in MATLAB 7.8 . The first five functional volumes in the acquisition were discarded to avoid transient spin saturation effects. Preprocessing included realignment and adjustment for movement related effects, co-registration of functional and anatomical data, spatial normalization into standard stereotactic MNI space and spatial smoothing using a Gaussian kernel of 8 mm full width at half maximum (FWHM). Subjects (n = 2) showing excessive scan-to-scan head motion (>4 mm) were excluded from the analyses. Additionally, the magnitude of head motion at each time point for translation and rotation parameters was obtained for each subject, and averaged within each group. No between-groups difference was evidenced using either the maximum head motion or the mean head motion measurements (ps >0.8), indicating similar movement patterns during scanning.t tests were used to assess the N2 vs. N0 contrast in the ADHD and control groups separately. Two-sample t tests were used for a direct comparison of the N2 vs. N0 contrast between ADHD and control subjects. Conjunction null analyses were used to identify the brain areas commonly activated in ADHD and controls in contrasts of interest Data were analysed using a mixed-effects model aimed at showing a stereotypical effect in the population from which the subjects were drawn t-tests to test for condition-specific effects within each group separately, or two-sample t-tests for between–group comparisons. In all the analyses presented above, the resulting set of voxel values for each contrast constituted a map of the t statistic [SPM(T)], thresholded at p<0.001 (uncorrected for multiple comparisons). Statistical inferences were then obtained after corrections at the voxel level using Gaussian random field theory corr <.05 corrected for multiple comparisons in the whole brain volume and a minimal cluster size of 20 voxels , or psvc <.05 corrected in a small spherical volume (radius 6–16 mm) around a priori locations of activation in structures of interest, taken from previous fMRI studies examining the N-back task in adults Additionally, psychophysiological interaction (PPI) analyses


Attention-deficit/hyperactivity disorder (ADHD) is one of common neurodevelopmental disorder often comorbid with epilepsy. There are no existing guidelines on how to manage these two conditions when they are comorbid. To identify relationship between epilepsy and ADHD and to know role of antiepileptics and safety of stimulant like methylphenidate in such conditions from existing literature, we searched articles published in clinical journals available online between 1990-2010, with these key words in medline:children, epilepsy, seizure, comorbid, ADHD, treatment. Relevant abstracts were further selected for their focus on current topic. Cross references were extracted. Finally relevant articles that included original research articles, reviews and abstracts of non-english literature were used. Children with epilepsy may manifest with symptoms of ADHD. Children with ADHD may develop epilepsy. Some antiepileptics like phenobarbitone, gabapentin, topiramate may not be helpful in controlling behavioral symptoms of ADHD. Stimulants are the main stay of pharmacotherapy for ADHD but there is risk of decreasing seizure threshold in children with comorbid epilepsy especially when their epilepsy is not well controlled. Existing evidence is not in favor of screening children with ADHD for EEG abnormality before starting stimulant therapy. Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder of childhood onset. It is being recognized for its impact on child development and on the family. This disorder is being treated by various health professionals, including pediatricians, psychiatrists, neurologists, internists, and general practitioners. Commonly used medications are stimulants, such as methylphenidate, amphetamine, and the nonstimulant drug atomoxetine. Carbamazepine and clonidine are used as non-FDA approved offlabel medications for ADHD in children and adolescents as an alternative to stimulants.2 Besides4Children with epilepsy are likely to have higher lifetime prevalence of depressive disorders, anxiety, and ADHD compared with those without epilepsy. The prev77Epilepsy in children is associated with behavioral problems, such as ADHD and cognitive impairments. Children with benign childhood epilepsy with centrotemporal spikes (BCECTS), complex partial seizures (CPS), frontal lobe epilepsy, rolandic epilepsy, and absence type of epileptic seizure may be more likely to show such symptoms.1112 Cogn1112New onset epileptic seizures lead to cognitive deterioration and certain epileptic seizures, such as CPS may cause more inattention problems in children with ADHD.16 In suc17Children with ADHD are predisposed to epileptic seizures. ChildrenSome studies have shown that methylphenidate and atomoxetine use in children with ADHD without a history of epileptic seizure is safe.23 HoweveThe number of children enrolled varied from 10 to 119 in studies that have tried to ascertain this in short term course. The duration of stimulant exposure varied from 8 weeks to 10 months in these randomized controlled studies. Many have used placebo and some compared the effects of methylphenidate with dextroamphetamine. Some studies have reported no increased seizure frequency or any major side effects in ADHD children with comorbid epilepsy.24–26Those who found increased seizure frequency while on methylphenidate have found different explanations: this happened (1) in those with uncontrolled epilepsy–29 and (However, the risk of epileptic seizure exists in those with history of epilepsy, having diseases involving the central nervous system, having metabolic disorders affecting the central nervous system, and being on psychotropics.30There is still a need for large sample-sized, randomized controlled studies to collect data on the safety and efficacy of stimulants in children with ADHD and epilepsy. As there is insufficient evidence, EEG screening is not recommended in children presenting with ADHD unless there are other clinical indications. Although evidence at this time shows that use of methylphenidate for the treatment of ADHD does not alter antiepileptic drug levels or seizure frequency, still the longer-term effects of methylphenidate itself and its effects on children with frequent epileptic seizures need further study.In cases where epilepsy and ADHD are comorbid, carbamazepine and lamotrigine may be more beneficial compared with other antiepileptics in that apart from the control of epileptic seizure they have better effects on attention and behavior. If there


Bartonella are gram-negative bacteria classified within the alpha-Proteobacteria. Over the last decade the number of identified Bartonella spp. has increased rapidly and the known diversity of the Bartonellaceae family continues to expand, as recently demonstrated in various mammals Bartonella species depends on their hosts and vectors. Mammalian species, such as cats, dogs, rodents and ruminants, are the main bartonellae reservoirs. Our objective was to detect and identify, by molecular methods, the presence of Bartonella species in wild rodents from the Lao PDR (Laos), a country where epidemiological and clinical studies of zoonoses are scarce.Bartonella.Rodents were trapped using cage and break-back traps and purchased from local markets in June and December 2006 in four Lao provinces. All specimens were photographed, vouchered  and identified subsequently (by KA) Total genomic DNA was extracted from livers and spleens with a QIAamp Tissue kit , as described by the manufacturer. Samples were handled under sterile conditions to avoid the risk of cross-contamination.Bartonella species DNA by the use of a real-time (RT) quantitative PCR targeting the ITS gene. Positive samples at screening were further studied by PCR amplification and DNA sequencing of the genes encoding the 16S–23S rDNA intergenic spacer (ITS), citrate synthase (gltA), β-subunit of the RNA polymerase (rpoB) using previously described primers and conditions Bartonella species were determined for each gene to assess the taxonomic position of Bartonella isolates at the species levels. Phylogenetic relationships among the studied bartonellae were inferred from sequence alignments of each gene and from concatenated gene sequences using the maximum parsimony and neighbour-joining methods within the MEGA version 3.1 software package .Samples were screened for the presence of Bartonella by RT-PCR. Positive and negative controls showed expected results in all tests. Using standard ITS PCR and sequencing we identified the presence of five Bartonella species, including B. phoceensis, B. elizabethae, B. tribocorum, and two new Bartonella species that we named Lao/Nh1 and Lao/Nh2, in three different regions of Laos  from 310 rodents and one tree shrew see . One hun of Laos . Lao/Nh1Bartonella species identification as the members of the genus Bartonella are fastidious bacteria that possess few phenotypic markers that are useful for species delineation. We used the gltA, the rpoB and the ITS genes to determine the taxonomic status of Bartonella strains from Laos as these genes have good discriminating power B. birtlesii and B. taylorii whereas Lao/Nh2 clustered with B. tribocorum. Finally, Lao/Nh1 was detected only in Rattus rattus collected from Luangnatha Province and Luang Prabang. It is yet unknown whether these Bartonella species strains from Laos are human pathogens and this should be investigated.Comparison of DNA sequences has been the most commonly used approach for Bartonella species in rodents in Lao PDR. We found a high prevalence of Bartonella spp. (25.5%), including B. elizabethae, B. tribocorum and B. phoceensis. B. elizabethae has been already isolated in small mammals from Bangladesh B. tribocorum in rodent fleas from China B. tamiae, a newly recognised pathogen isolated from three human patients from Thailand B. phoceensis, it is its first molecular detection in this part of the world.To the best of our knowledge, this is the first study of the prevalence of lla spp. 5.5%, incBartonella spp. were identified in rodents derived from both agrarian and urban environments. Rodents are abundant in both contexts in Laos, hence a large proportion of the human population lives in close contact with rodents. Accordingly, it is possible that some unknown diseases in Laos may be caused by Bartonella spp. Further investigations are warranted in order to isolate these new Bartonella spp. and to determine if they can cause any clinical manifestations.


N = 170), their parents (N = 310), and ethnically matched controls (n = 180) was used for genotyping followed by population- and family-based analyses by the UNPHASED program. DRD4 sites showed significant difference in allelic frequencies by case-control analysis, while DDC and COMT exhibited bias in familial transmission (P < 0.05). rs3837091 “AGAG,” rs3735273 “A,” rs1799732 “C,” rs740603 “G,” rs165599 “G” and single repeat alleles of rs4646984/rs4646983 showed positive correlation with co-morbid characteristics (P < 0.05). Multi dimensionality reduction analysis of case-control data revealed significant interactive effects of all four genes (P < 0.001), while family-based data showed interaction between DDC and DRD2 (P = 0.04). This first study on these gene variants in Indo-Caucasoid ADHD probands and associated co-morbid conditions indicates altered dopaminergic neurotransmission in ADHD.Contribution of genes in attention deficit hyperactivity disorder (ADHD) has been explored in various populations, and several genes were speculated to contribute small but additive effects. We have assessed variants in four genes, DDC (rs3837091 and rs3735273), DRD2 , DRD4 (rs4646984 and rs4646983), and COMT (rs165599 and rs740603) in Indian ADHD subjects with comorbid attributes. Cases were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV-TR after obtaining informed written consent. DNA isolated from peripheral blood leukocytes of ADHD probands ( Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by age inappropriate inattentiveness, hyperactivity, and impulsivity . ComorbiStrong genetic basis of ADHD is supported by twin, adoption, or family-based studies , 5. A maAction of DA is mediated through DA receptors (DRD) grouped in two families based on the activation  or inhibition  of adenylate cyclase in response to ligand binding , 9. The Genes encoding for enzymes involved in the catecholaminergic system like catechol-O-methyl transferase (COMT) , 20, dopIn the Indo-Caucasoid ADHD probands, DRD4, DAT1, MAOA, COMT, and DBH gene variants showed significant association with the disorder . HoweverN = 170) from the out-patient department of Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, Kolkata, based on (a) DSM-IV-TR criteria [We recruited ADHD probands N = 70 from tcriteria ; (c) intcriteria  for chilcriteria . Mean agN = 180; mean age 19.7 years ± 7.94 SD; and male to female ratio 10 : 3), evaluated following the DSM-IV-TR criteria [A control group (http://compbio.cs.queensu.ca/F-SNP/).Nine polymorphic sites in four genes, that is, DDC (rs3837091 (AGAG Ins→Del) and rs3735273 (G→A)), DRD2 (rs1800496 (C→T), rs1801028 (C→G), and rs1799732 (C→Del)), DRD4 (rs4646984 (429 bp/549 bp) and rs4646983 (286 bp/298 bp)), and COMT (rs740603 (G→A) and rs165599 (G→A)), were selected based on their association with ADHD , 25–28 ohttp://dx.doi.org/10.1155/2013/918410.Peripheral blood was collected from ADHD probands, their parents and controls for isolation of genomic DNA . Detailshttp://wbiomed.curtin.edu.au/genepop/) was used to calculate allelic and genotypic frequencies followed by analyses for Hardy-Weinberg equilibrium (HWE). For case-control analysis, we have used the program COCAPHASE, which is a part of a suite of programs UNPHASED [www.hutchon.net/ConfidOR.htm). Relative risk calculator was used to calculate the relative risk (RR) and its confidence interval (http://www.hutchon.net/ConfidRR.htm). While OR portrays the strength of association between two binary data values compared symmetrically, RR describes the likelihood of developing disease in an exposed group compared to a nonexposed group. Data obtained was subjected to both population-as well as family-based association analyses. The GENEPOP program (web version 3.4)  was calculated using a 1000-fold permutation test to compare observed testing accuracies with those expected under the null hypothesis of no association. Multifactor dimensionality reduction (MDR) program  was usedP values for each statistic were obtained by fixed  and nonfixed permutation tests .For the family-based data, we have analyzed only the trio families by MDR phenomics version 1.0 . In absers1800496 and rs1801028 were found to be nonpolymorphic after analyzing 100 control subjects and 30 families with ADHD probands; only the “C” variant was detected , and we P = 0.09), which could be due to absence of homozygous genotype of the single repeat variant in the control subjects . Further analysis revealed that this bias was due to maternal overtransmission of the “AGAG” allele, more specifically to male probands . rs740603 “G”  also showed a bias in transmission to ADHD cases  of this haplotype from the parents (Table S4). The rs4646983-rs4646984 2R-2R haplotype was present predominantly in control individuals (Table S3). Haplotype “G-A” of rs165599-rs740603 exhibited higher transmission  to ADHD probands (Table S4). Haplotype analysis showed lower frequency of rs3837091-3735273 “Del-G” in ADHD cases (Table S3) which could be primarily due to significant nontransmission (Major comorbidities observed in ADHD children from eastern India are LD (44%), ODD (33%), CD (31%), and MD (16%). Substance abuse disorder, tic disorder, and AD were found in only few cases and excluded from further analysis. Comparative analysis of ADHD probands subgrouped on the basis of co-morbid characteristics revealed the following observations.χ2 = 7.6; P = 0.02). Further, there was an overtransmission of the “AGAG” allele (P = 0.006) . On the other hand, maternal overtransmission of the “AGAG” allele was significant in ADHD + CD . In ADHD + MD, “AGAG/AGAG” genotype showed lower frequencies in parents as well as probands as compared to the control population .By population-based analysis, we have noticed significant differences in “AGAG” allele frequency for rs3837091 in ADHD comorbidity ; the “AG= 0.006) , which wχ2 = 6.5 and 12.3; P = 0.01 and 0.002 resp.) OR was also high in this group (2.17).rs3735273 showed significant differences in allelic and genotypic frequencies in ADHD + CD in comparison to controls; “A” allele and “AA” genotype frequencies were higher in probands  and “CC” genotype were overrepresented in ADHD + LD  as well as in ADHD + MD  with a noticeably high OR. Family-based analyses showed overtransmission of the “C” allele . Other comorbidities failed to show any significant contribution  as compared to the control population (P = 0.02) familial overtransmission  allele of rs4646984 showed higher frequencies , ADHD + ODD , and ADHD + MD  by population-based analysis  and genotypic (1R1R) frequencies in ADHD + CD . Furthermore, in ADHD + LD, “GG” genotype showed higher frequencies as compared to the control population . Lack of any association was noticed for other co-morbid conditions  and “GG” genotype  were overrepresented in ADHD + ODD when compared to control. In ADHD + MD also, “G” allele  and “GG” genotype  showed significant overrepresentation. Statistically significant overtransmission of the “G” allele  from parents to ADHD + MD was also noticed  between rs3837091, rs1799732, rs4646984, and rs740603 .Gene-gene interaction analysis by MDR describes percentage of entropy (information gain—IG) by each factor or by 2-way interaction; nodes indicate independent main effect, while connecting lines between the nodes indicate interactive effect contributed by pairwise combinations. All the positive values indicate a gain in effect, whereas negative values indicate redundancy or lack of any synergistic effect. In the present study, positive nodal IG values obtained by case-control analysis indicate significant main effect of rs3735273 followed by rs3837091, rs1799732, rs4646984, and rs740603 in ADHD . MDR anaP = 0.04).Gene-gene interaction analysis using family-based data  revealedP = 0.008), the CVC value was insignificant (Table S6). In ADHD comorbidity group, rs3837091 exhibited independent main effect followed by rs3735273, rs1799732, rs4646983, and rs740603 . Though interaction between rs3837091, rs17997332, rs740603 showed a trend to be significant , we have noticed significant main effect of rs3837091 followed by rs3735273, rs4646983, rs1799732, and rs4646984. No interaction was noticed between the sites for this group (Table S6). In ADHD + LD, rs3837091 showed significant main effects followed by rs3735273, rs1799732, rs4646983, and rs4646984 . In this group also, no significant interaction between the sites was noticed (Table S6). ADHD + MD cases  exhibited significant main effect for rs3837091 followed by rs4646983, rs740603, rs4646984, and rs1799732. Two locus interaction analyses revealed lack of significant interaction (Table S6). P values and CVC = 10 (Table S6). In the ADHD + ODD , independent main effects were observed for rs3837091 followed by rs740603, rs165599, rs3735273, and rs1799732. Positive values for the corresponding connecting lines among DDC (rs3837091 and rs3735273), DRD2 (rs1799732), and COMT (rs165599 and rs740603) indicated interaction between the sites for this group . Strong interaction between DDC, DRD2, and COMT was also documented from significant P > 0.05, Table S7).Analysis of family-based data by MDR-PDT failed to show any statistically significant result in any of these groups after corrections for multiple testing  decarboxylation of L-3,4 dihydroxyphenylalanine (L-DOPA) to dopamine, (2) 5-hydroxytryptophan (5HTP) to serotonin, and (3) L-tryptophan to tryptamine. Both DA and serotonin neurotransmitter systems have been reported to be altered in ADHD [DDC with ADHD in a number of Caucasian populations [DDC showed association with ADHD inattentive subtype [DDC variants showed association with both childhood and adult ADHD [In silico analysis of rs3837091 and rs3735273 by F-SNP failed to show any alteration in function of the DDC gene. Based on the biased maternal transmission, we may infer that rs3837091 may have some role in the etiology of ADHD, especially in male probands, and could be the reason for higher occurrence of ADHD + CD. It can be speculated that rs3837091 is in association with another functional site in DDC and further investigation is warranted to find out the actual role of DDC in the etiology of ADHD.Enzyme encoded by the in ADHD , making  in ADHD . Genome-ulations . In the  subtype . In Spanult ADHD , while iult ADHD . rs37352ult ADHD . In the DRD2 gene have shown association with ADHD in probands from Finland [Pharmacological intervention of several neuropsychiatric and neurologic disorders essentially relies on the modulation of function of the DRD2 receptor. SNPs in the  Finland . Associa Finland  as well  Finland  schizoph Finland . Since t Finland . However Finland . In the  Finland . This va Finland , and ass Finland . In the DRD2, -141C Ins/Del variant, rs1799732, alters transcriptional activity of the promoter thus regulating expression of the receptor [Another functional variant in the receptor  and has receptor . Responsreceptor . While nreceptor . Frequenreceptor , which iDRD4 as a candidate gene for ADHD [N = 70) and Italian delusional disorder patients (N = 59), respectively [P = 0.04; power = 54%  α at 0.05) along with higher frequency of the 2R-2R haplotype in control samples (P = 0.05) indicates some protective role of this allele in the studied population. Whether this diversity in allelic association, in absence of any allelic flip, is due to a difference in association with the disorder or is generated due to type I error in different studied population merits further investigation in large cohort of subjects.DRD4 receptor is predominantly expressed in the frontal lobe regions of the brain, a region thought to be involved in the etiology of ADHD . Associafor ADHD –15, 21. for ADHD , showed for ADHD , and USAfor ADHD , 56. On for ADHD . A studyfor ADHD . A 12 bpfor ADHD , was alsents N = , respectCOMT gene, predicted to alter transcriptional regulation (F-SNP), though failed to show any association with ADHD in Caucasian subjects from Finland [P = 0.0005) [COMT, predicted to affect gene expression [COMT haplotypes in boys and girls [P = 0.03), while maternal transmission to male probands was nominal only (P = 0.09). Marginally significant higher occurrence of the “G” was also observed in ADHD + ODD by population-based analysis. Higher occurrence of the “G” allele as well as “GG” genotype of rs165599 was also noticed in ADHD + LD probands. On the other hand, haplotype analysis showed a nominal bias in overtransmission of rs165599-rs740603 “G-A” (P = 0.04) which failed to be significant by case-control comparison. Earlier investigators reported an association of rs165599 “A” with anxiety spectrum disorder [COMT helps in the metabolism of DA, adrenalin, and norepinephrine and has been implicated in the etiology of substance abuse, schizophrenia, and novelty seeking, as well as ADHD. A number of investigations have been carried out on a functional variant, Val/Met polymorphism, at codon 158 , 20, and Finland  and Irel 0.0005) . Anotherpression , showed pression . On the pression . The G-Apression . Sexuallnd girls  and strond girls  have alsdisorder . Since odisorder .DBH rs1108580 and DRD4 rs1800955, while the DRD4 exon 3 VNTR, DAT1 3′UTR and intron 8 VNTR, MAOA u-VNTR, rs6323, COMT rs4680, rs362204, DBH rs1611115, and rs1108580 were found to exert strong independent effects [DRD4 and DAT1 (SLC6A3), while monoaminergic system genes showed significant interaction with ADHD symptoms [DRD2-DRD4 was found to be associated with development of CD and adult antisocial behavior in males [COMT and DRD4 [DRD2 and COMT was found to hamper working memory [DRD2 and COMT was noticed in ADHD + ODD, while in other groups, independent main effects of these sites were observed. Statistically significant interaction of DDC rs3837091 with DRD2 rs1799732, DRD4 rs4646984, and COMT rs740603 was also noticed by population-based analysis. Further, interaction of DDC rs3837091 with DRD2 rs1799732 was strong in families with ADHD probands; the P value remained statistically significant even after correction for multiple testing. DRD4 and DDC also exhibited significant main effects. While both DDC and COMT are important for neurotransmitter metabolism, COMT also plays vital roles in catecholestrogens and catechol-containing flavonoids. Furthermore, ADHD is hypothesized to be caused by an interaction of different genetic as well as environmental factors. It may be quite probable that the variants we found to be associated with ADHD have relatively small effect sizes keeping with the multifactorial polygenic etiology of ADHD [In an earlier investigation on the Indo-Caucasoid ADHD probands, we have noticed additive effects of symptoms . On the and DRD4 . Alternag memory . In the  of ADHD . The othDRD2 rs1799732 “C” allele. Decreased frequency of the rs1799732 “Del” allele was speculated to contribute to an elevated DRD2 density leading to DA hyperactivity [DRD2 and COMT was found to hamper working memory, a trait affected in ADHD probands [Altered dopaminergic neurotransmission is implicated in ADHD based on the presenting clinical features of probands, available animal models, and pharmacotherapeutics , 10, 46.activity . In vivoactivity . Furtherprobands . On the DDC, DRD2, DRD4, and COMT variants in individuals with ADHD and those exhibiting different co-morbid conditions. In our earlier investigation in this ethnic group, we have observed a trend for alteration in dopaminergic neurotransmission in ADHD probands [This association analysis on Indo-Caucasoid subjects with ADHD explored gene variants studied for association with different behavioral disorders. In this preliminary investigation, with limited number of ADHD probands, we have also studied association with different co-morbid conditions that are frequently observed in ADHD patients. The suggested reason for these comorbidities to be so common in ADHD subjects was hypothesized to be due to sharing of a number of gene variants . As a suprobands , 12. TheTable S1: Details on the procedure used for genotyping the studied sites.Table S2: Allelic transmission from parents to probands.Table S3: Case-control analysis of haplotypic frequencies.Table S4: Transmission of haplotypes from parents to probands.Table S5: Gene-gene interaction analyzed using case-control dataset.Table S6: Gene-gene interaction analyzed in ADHD cases with co-morbid features.Table S7: Gene-gene interaction analyzed in families with ADHD probands exhibiting various co-morbid features.Figure S1: Gene-gene interaction analyzed for co-morbid disorders using case-control dataset.Click here for additional data file.


To the Editor: Domestic cats and human body lice have been identified as the vectors of Bartonella henselae and B. quintana, respectively, the primary sources of Bartonella-associated human diseases . Blood samples from each of the trapped mammals were frozen in liquid nitrogen in the field and subsequently stored at –70ºC before bacteria isolation. Bacteria isolation was performed as previously described . Polymerase chain reaction (PCR) was performed by using two oligonucleotides specific for the citrate synthase (gltA) gene of B. henselae Houston 1, primers BhCS 781.p and BhCS 1137.n. Negative and positive controls (double-distilled H2O and DNA from cultures of B. henselae) were used in each PCR run. Products of the correct size were purified  and sequenced with the same primers, BhCS 781.p and BhCS1137.n., in both directions, with the Cy5/Cy5.5 Dye Primer Cycle Sequencing kit on a Long-Read Tower sequencer . Three hundred thirty-eight base-pair sequences of the gltA gene were obtained and compared with sequences of other known Bartonella species in GenBank by using the nucleotide BLAST program . Isolates identified as Bartonella species were obtained from 21 of the 70 blood cultures. All were isolated from A. flavicollis, and one was isolated from Dryomys nitedula. In addition, all were isolated from the first site (Nevrokopi village), and one was isolated from the second site (Pramanta village).This study investigated the potential for infection from Bartonella isolates, eight genotypes were found. Among these isolates, one (AY 435102 isolated from A. flavicollis trapped in Pramanta), was identical to ma106up strain, isolated from Microtus agresti (AF391789); another (AY 435103 isolated from A. flavicollis trapped in Nevrokopi), was identical to af82up strain (AF391788), also isolated from A. flavicollis  and representing four novel genotypes, was 98% similar to B. taylorii  gltA gene. The second group, consisting of seven isolates that shared the same genotype (AY 435114-AY435120 isolated from A. flavicollis), was 99% similar to B. birtlesii (AF 204272 isolated from Apodemus spp.). The third group consisted of two isolates that shared the same genotype ; this group was 97% similar to B. grahamii strain V2 (Z70016 isolated from Neomys fodiens).Within these 21 Bartonella in small mammals in Greece. We found that 31.3% of the examined mammals were infected with Bartonella spp. The prevalence of culture-positive infections differed between the two sites (20/57 versus 1/13), although both are mountain areas with similar environmental and climatic conditions. A high prevalence of Bartonella infection in small mammals also has been described in other countries such as the United States , as well as in Greece (61/70). Identical Bartonella strains were isolated from A. flavicollis and Microtus agresti in both countries. Unlike Sweden, where the most frequent genotype was B. grahamii, in this study no isolate was identical to any Bartonella species known to cause human diseases. However, B. elizabethae was first isolated from a patient with endocarditis, and nothing was known concerning the organism’s natural history until it was isolated from a rodent captured in Peru . The public health relevance of Bartonella infections in small mammals in Greece compared with other countries remains to be defined.The occurrence and distribution of


In this journal, Holden, Jenkins-Jones, Poole, Morgan, Coghill and Currie , CAPMH 7:34, 2013, report on the prevalence and financial costs of treating people with attention deficit hyperactivity disorder (ADHD) in the UK over the last ten years. We commend the authors on their thorough cost analysis, and discuss differences in prevalence estimates of diagnosed ADHD, that is the proportion of the child population with an ADHD diagnosis, which varies dramatically between studies. We also discuss the reasons for this. Regional variation in application of diagnostic criteria and clinical subjectivity are likely partial explanations. Holden, Jenkins-Jones, Poole, Morgan, Coghill and Currie  perform Holden et al. report the UK prevalence of diagnosed ADHD at 0.5% in 2009 for registered patients aged 6 to 17 years, which is a surprisingly low estimate in comparison with the prevalence of 9.5% for parent-reported diagnoses of ADHD among children aged 4-17 years from USA’s Center for Disease Control (CDC) in 2007 [Diagnoses, of course, particularly child, psychiatric diagnoses, are subject to the vagaries of fashion. Indeed, ADHD has been described as the ‘diagnosis du jour’ by some scholars . A more diagnosed ADHD may reflect differences in recognition rather than true differences in levels of underlying impairment. DSM criteria, most often used in the US, are less stringent than the ICD-10 criteria that are more often applied in Europe, which may go some way toward explaining higher rates of ADHD reported in the USA [Even among rigorous epidemiological studies, differences in the samples selected and measures used can make comparisons between figures all but meaningless. Polanski and colleagues, for example, reported prevalence estimates that varied from 1.5% to 25%, from studies across the world . These dThere are on going debates about whether the prevalence of ADHD really is lower in the UK than in the US . Holden Perhaps the more pertinent question is not ‘what is the prevalence of diagnosed ADHD’, but whether it is helpful for children to be diagnosed, or for families to have their child diagnosed with ADHD / receive treatment. Making this call involves weighing up the costs versus the benefits of diagnosis of ADHD for each individual child and family. Certainly, for children who are severely impaired, numerous studies show that a range of outcomes at adolescence and adulthood are negatively affected. These include lower academic attainment, fewer employment prospects, and less chance of forming stable long term relationships, as well as increased odds of ending up with a criminal record -17. TherThe authors have no conflict of interests.Both authors have been involved in drafting the manuscript or revising it critically for important intellectual content and have given final approval of the version to be published.