Epidemiology of uncontrolled epilepsy in the Al-Kharga District,New Valley,Egypt

BackgroundDespite advances in treating epilepsy, uncontrolled epilepsy continues to be a major clinical problem. Therefore, this work aimed to study the epidemiology of uncontrolled epilepsy in Al-Kharga District, New Valley.MethodsThis study was carried out in 3 stages via door-to-door screening of the total population (62,583 persons). All suspected cases of epilepsy were subjected to case ascertainment, conventional ElectroEncephaloGraphy (EEG), and the Stanford-Binet Intelligence Scale. Patients who had been receiving suitable anti-epileptic drugs (AEDs) over the previous 6 months and were having active seizures were considered uncontrolled, according to Ohtsuka et al.²³ The patients underwent serum AED level estimation, video EEG monitoring, and brain MRIs. Fifty age- and gender-matched patients with controlled epilepsy were chosen for statistical analysis and compared with true intractable patients.ResultsA total of 437 patients with epilepsy were identified, 30.7% of whom (n = 134/437) were uncontrolled, with a prevalence of 2.1/1000. A total of 52.2% of uncontrolled patients (n = 70/134) were inappropriately treated, while 47.8% (n = 64/134) were compliant with appropriate treatments. Video monitoring EEG of compliant uncontrolled patients demonstrated that 78.1% patients (n = 50/64) had definite epilepsy, while 21.9% (n = 14/64) had psychogenic non-epileptic seizures (PNES). A logistic regression analysis revealed that status epilepticus, focal seizures, and mixed seizure types were risk factors for intractability.     

Philtrum length and intercommissural distance measurements at mixed dentition period

Anthropometric measurements of the lip and mouth are of great importance in clinical dysmorphology as well as reconstructive plastic surgery. In this study, the philtrum length (PhL) and intercommissural distance (ICmD) nomograms for Egyptian children in the mixed dentition period were established. A group of 1,338 Egyptian students in primary schools (735 boys and 603 girls) were included in the study. The students were at mixed dentition period and their ages ranged from 7 to 12 years. Anthropometric norms of PhL and ICmD were developed with significant sex difference in certain groups. A ratio between PhL and ICmD was developed. These data will help facilitate both objective and subjective evaluation of the lip and mouth for proper diagnosis of orofacial anomalies and variations as well as for ideal treatment plans.     

“Anosmia” the mysterious collateral damage of COVID-19

Journal of NeuroVirology - COVID-19 pandemic spreads worldwide, with more than 100 million positive cases and more than 2 million deaths. From the beginning of the COVID-19 pandemic, several...     

Genome scanning of Amazonian Plasmodium falciparum shows subtelomeric instability and clindamycin-resistant parasites

Here, we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos region using genome scanning, a microarray-based technique that delineates the majority of single-base changes, indels, and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon bears a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes, indicating mutations arising during self-mating or mitotic replication. The data also reveal that one or two meioses separate different isolates, showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pairwise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species, but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase of clindamycin EC₅₀ in strains harboring one of these mutations. This evidence of clindamycin-resistant parasites in the Amazon suggests that a shift should be made in health policy away from quinine + clindamycin therapy for malaria in pregnant women and infants, and that the development of new lincosamide antibiotics for malaria should be reconsidered.The World Health Organization (WHO) campaign to eradicate malaria in the 1950s and 1960s was initially largely successful in decreasing the burden of malaria. Drug failure eventually led to a resurgence in the number of malaria cases in the 1990s and caused vast numbers of deaths that could have been avoided through a better appreciation of the prevalence of drug-resistant malaria and more informed choices of first-line drugs (Greenwood et al. 2008). While malaria deaths are now likely to decline, primarily because of the introduction of artemisinin-based combination therapy (ACT) as well as increased insecticide spraying and the use of bed nets (Greenwood et al. 2008), this may only be temporary. Indeed, there has been a general increase in the parasite clearance times in ACT-treated Plasmodium falciparum malaria cases from near the Thai–Cambodian border, suggesting that case numbers may soon begin increasing (Dondorp et al. 2009).Remarkably, although artemisinin is used on tens of millions of individuals annually, we have little idea about how it acts or which genes contribute to resistance, confounding the community''s ability to monitor the spread of resistance using molecular markers and to deploy new therapies (Eastman and Fidock 2009). The fact that the genes involved in artemisinin resistance are not known is due to a variety of problems, including the fact that in vivo resistance has not been replicated in vitro (Dondorp et al. 2009). Additionally, the association of phenotypes with genotypes in P. falciparum is hampered by the difficulties in performing complementation studies due to extremely low transfection efficiencies and the fact that laboratory crosses of drug-sensitive and drug-resistant P. falciparum cannot be easily performed. Thus, it took more than 40 yr between the identification of chloroquine resistance in the field (Harinasuta et al. 1965) and confirmation that resistance is due to mutations in the chloroquine resistance transporter (pfcrt, MAL7P1.27) (Wellems et al. 1990; Fidock et al. 2000; Sidhu et al. 2002). While the recombinant progeny from one of the three extant crosses (Walliker et al. 1987; Wellems et al. 1990; Hayton et al. 2008) have most famously been used to map chloroquine resistance (Wellems et al. 1990), they have been used to map loci contributing to a wide variety of phenotypes that distinguish parental clones. For example, they have already been scored for a variety of different phenotypes that are related to drug sensitivity, including antifolate sensitivity (Wang et al. 2004b), quinine sensitivity (Ferdig et al. 2004), expression levels (Gonzales et al. 2008), and plasmodial surface ion channels (Alkhalil et al. 2009), but they could be scored for any phenotype that quantitatively distinguishes the parental strains Dd2 and HB3, such as propensity to mutate in the laboratory (Rathod et al. 1997). However, there are a limited number of phenotypes that distinguish these two laboratory strains that were derived from patients 40 yr ago. While more crosses would provide valuable data for many researchers interested in parasite genetics, there are ethical considerations associated with using primates in research. An alternative to creating new recombinant progeny is to find existing recombinant isolates that arose from recent meioses occurring in humans. Such parasites might be identified by performing full-genome analyses on parasites from a limited geographical area and could provide the malaria community with an unprecedented number of parasites differing in a variety of phenotypes for use in linkage or quantitative trait locus (QTL) studies.One attractive group of parasites for full genome investigation is from the Peruvian Amazon. Due to the low transmission rates it is expected that parasites isolated from an individual will be from a single clone infection. In addition, malaria was eradicated in the 1960s in this region but re-emerged with epidemics in the early 1990s (Aramburu Guarda et al. 1999; Branch et al. 2005), suggesting that the genomes might contain signatures of selective sweeps (Wootton et al. 2002; Roper et al. 2004). At first, malaria in this region was treated with chloroquine (first-line), sulfadoxine-pyrimethamine (second-line), and quinine with clindamycin or tetracycline (third-line) (Aramburu Guarda et al. 1999), but the emergence of resistance resulted in widespread chloroquine and antifolate treatment failure (Durand et al. 2007). Today, malaria remains hypoendemic with low levels of seasonal transmission of P. falciparum and P. vivax parasites in the region surrounding Iquitos, Peru (Roshanravan et al. 2003). Previous studies of parasites in the region describe only one or two independent haplotypes for important drug-resistance genes, suggesting a limited number of founders for this population (Bacon et al. 2009) and suggest that we might find recombinant progeny in this region.In this study, we performed genome scanning on 14 P. falciparum patient isolates from a limited geographical region. We show that the parasite population in the Peruvian Amazon is very closely related, with combinations of only two to four different genotypes for drug resistance genes, suggesting at most four parental haplotypes. Furthermore, some parasites taken from different patients who presented with symptoms were essentially clones of one another, while others were recent meiotic siblings that could be useful in linkage studies or eQTL analyses. Unexpectedly, genome scanning also revealed uncharacterized mutations in the apicoplast 23S rRNA that distinguished some Peruvian strains from the reference strain, 3D7. Because one of these mutations had been previously associated with lincosamide antibiotic resistance in the chloroplast and many bacterial species (Vester and Douthwaite 2001), sensitivity testing was performed revealing that the parasites harboring the mutation had indeed become resistant to clindamycin, a drug used in combination with quinine to treat pregnant women and infants for malaria in Peru. These are the first documented cases of resistance to this class of drugs in malaria and suggest that the use of lincosamide drugs in treating malaria should be reconsidered.     

Suppression of human cortico-motoneuronal excitability during the Stop-signal task

ObjectiveTo investigate whether motor suppression is an active process, and to clarify its somatotopic organization, we investigated cortico-motoneuronal excitability using transcranial magnetic stimulation (TMS) during the Stop-signal task.MethodsSubjects were asked to press a button following a Go cue; a Stop-signal followed the Go cue by a certain time delay in 25% of trials, indicating to subjects that they were not to press the button. TMS was given to the primary motor area of the left or right-hand or leg at variable time delays. Motor evoked potentials (MEPs) were recorded from the hand and leg muscles bilaterally.ResultsWhen TMS was delivered 400 ms after the Go cue, there was significant suppression of the MEPs of the bilateral hand and leg muscles during successful Stop trials, but not during failed Stop trials.ConclusionsThe voluntary stopping of movement in the Stop-signal task is an active process, which likely suppresses not only the cortico-motoneuronal excitability of the task-performing hand, but also causes the widespread suppression of the motor system.SignificanceStudies in the normal physiology of response inhibition would be of help in understanding the pathophysiology of neuro-psychiatric disorders associated with deficits in motor suppression.