Systems for deep brain stimulation: review of technical features.

The use of deep brain stimulation (DBS) is an important treatment option for movement disorders and other medical conditions. Today, three major manufacturers provide implantable systems for DBS. Although the underlying principle is basically the same for all available systems, the differences in the technical features vary considerably. This article outlines aspects regarding the technical features of DBS systems. The differences between voltage and current sources are addressed and their effect on stimulation is shown. To maintain clinical benefit and minimize side effects the stimulation field has to be adapted to the requirements of the patient. Shaping of the stimulation field can be achieved by the electrode design and polarity configuration. Furthermore, the electric signal consisting of stimulation rate, stimulation amplitude and pulse width affect the stimulation field. Interleaving stimulation is an additional concept, which permits improved treatment outcomes. Therefore, the electrode design, the polarity, the electric signal, and the concept of interleaving stimulation are presented. The investigated systems can be also categorized as rechargeable and non-rechargeable, which is briefly discussed. Options for interconnecting different system components from various manufacturers are presented. The present paper summarizes the technical features and their combination possibilities, which can have a major impact on the therapeutic effect.

Cleft Lip and Palate: Demographic Patterns and the Associated Communication Disorders.

PURPOSE: This study investigated demographical characteristics, health status, and associated communication disorders in patients with orofacial clefts (OFCs) in Northern Jordan. METHODS: A retrospective study of 226 cleft patients and their families was carried out between March 2012 and September 2016 at the Speech and Hearing Clinic and the Maxillofacial Center at King Abdullah University Hospital. Data were collected by interviewing patients and caregivers, having patients or caregiver to complete a questionnaire and reviewing the patient's medical records. The frequencies of OFC type, demographic, health status, and communication disorders variables were calculated. χ analysis was used to test for significance of associated demographic and communication disorders variables with OFC type. RESULTS: Results revealed higher percentage of males compared with female patients. The majority of OFC patients were born to families who lived in urban areas, obtained high school diploma or lower educational level, lived below poverty cutoff, and showed nonconsanguineous marriages. Most mothers took the prescribed pregnancy supplements. Only one-third of the families received health education and reported other incidences of OFCs. Twenty percent of the patients had other congenital anomalies, 80% experienced dysphagia prior to the cleft repair, dropped to 14% after the repair. Higher percentage of patients with isolated cleft palate and cleft lip and palate exhibited hearing loss, hypernasality, articulation and phonological disorders, and dysphagia compared with those with cleft lip only. None of the demographic variables was associated with OFC type. CONCLUSIONS: Data suggested that families who had children with OFCs displayed poor socioeconomic status and low educational level which may impede the delivery of health education by health practitioners. Increased risk of comorbid communication disorders and malformations in OFC patients must be emphasized and disseminated to health professionals involved in the management of patients with OFC.

Oldest evidence of abundant C4 grasses and habitat heterogeneity in eastern Africa.

The assembly of Africa's iconic C4 grassland ecosystems is central to evolutionary interpretations of many mammal lineages, including hominins. C4 grasses are thought to have become ecologically dominant in Africa only after 10 million years ago (Ma). However, paleobotanical records older than 10 Ma are sparse, limiting assessment of the timing and nature of C4 biomass expansion. This study uses a multiproxy design to document vegetation structure from nine Early Miocene mammal site complexes across eastern Africa. Results demonstrate that between ~21 and 16 Ma, C4 grasses were locally abundant, contributing to heterogeneous habitats ranging from forests to wooded grasslands. These data push back the oldest evidence of C4 grass-dominated habitats in Africa-and globally-by more than 10 million years, calling for revised paleoecological interpretations of mammalian evolution.

The evolution of hominoid locomotor versatility: Evidence from Moroto, a 21 Ma site in Uganda.

Living hominoids are distinguished by upright torsos and versatile locomotion. It is hypothesized that these features evolved for feeding on fruit from terminal branches in forests. To investigate the evolutionary context of hominoid adaptive origins, we analyzed multiple paleoenvironmental proxies in conjunction with hominoid fossils from the Moroto II site in Uganda. The data indicate seasonally dry woodlands with the earliest evidence of abundant C4 grasses in Africa based on a confirmed age of 21 million years ago (Ma). We demonstrate that the leaf-eating hominoid Morotopithecus consumed water-stressed vegetation, and postcrania from the site indicate ape-like locomotor adaptations. These findings suggest that the origin of hominoid locomotor versatility is associated with foraging on leaves in heterogeneous, open woodlands rather than forests.

The nucleolus: the magician's hat for cell cycle tricks.

The nucleolus, for decades considered a ribosome factory and site for ribosomal RNA synthesis and processing, has recently acquired new fame. Analyses of proteins important for cell-cycle regulation have shown that this organelle is used to sequester proteins, thereby inhibiting their activity.

Meiosis: how to create a specialized cell cycle.

During the meiotic cell cycle, a single round of DNA replication precedes two nuclear divisions. Recent work has shown that the proteins controlling the mitotic cell cycle are either replaced by homologous proteins only expressed during the meiotic cell cycle or modulated by meiosis-specific factors to bring about this specialized cell cycle.

Together until separin do us part.

Loss of sister-chromatid cohesion triggers chromosome segregation. Several recent reports show that the protease Esp1 cleaves the cohesin subunit Scc1/Mcd1 to induce sister-chromatid segregation in yeast and vertebrates. This finding indicates that cohesin cleavage may control sister-chromatid separation in all vertebrates.

Oral candidal colonization in cleft patients as a function of age, gender, surgery, type of cleft, and oral health.

PURPOSE: To assess the colonization rate of oral Candida species and the influence of age, gender, oral health status, number of surgeries, and type of cleft. PATIENTS AND METHODS: A prospective study of 60 patients with cleft and 60 control subjects was carried out at the Cleft Centre at King Abdullah University Hospital and the Maxillofacial Unit at Jordan University of Science and Technology between October 2007 and June 2008. Oral health was assessed using the Gingival, Plaque, and Decayed, Missing, and Filled (DMFT/dmft) indexes using World Health Organization criteria. A culture swab was obtained from the tongue and buccal and palatal mucosae. Candida albicans and other Candida species were identified using the germ tube test and the automated biochemical test panel VITEK. RESULTS: The colonization rate of Candida in patients with cleft (63.3%) was significantly higher than in healthy control subjects (18.3%). The colonization rate of Candida and the distribution of C albicans varied with age but were not significantly associated with gender in patients with cleft and healthy controls. The candidal colonization rate was highest in patients with cleft who had at least 3 surgeries (78.2%) and in patients with bilateral clefts (77.7%). Patients with cleft had a significantly poorer health status than healthy controls; however, this was not influenced by the type of the cleft or the number of surgeries. CONCLUSION: Patients with cleft had a significantly higher rate of oral candidal colonization compared with control subjects, which varied with age, type of cleft, and the number of surgical interventions. Oral health status was significantly poorer in patients with cleft.

Non-centrosymmetric superconductor Th[Formula: see text]Be[Formula: see text]Pt[Formula: see text] and heavy-fermion U[Formula: see text]Be[Formula: see text]Pt[Formula: see text] cage compounds.

Unconventional superconductivity in non-centrosymmetric superconductors has attracted a considerable amount of attention. While several lanthanide-based materials have been reported previously, the number of actinide-based systems remains small. In this work, we present the discovery of a novel cubic complex non-centrosymmetric superconductor [Formula: see text] ([Formula: see text] space group). This intermetallic cage compound displays superconductivity below [Formula: see text] K, as evidenced by specific heat and resistivity data. [Formula: see text] is a type-II superconductor, which has an upper critical field [Formula: see text] T and a moderate Sommerfeld coefficient [Formula: see text] mJ [Formula: see text] [Formula: see text]. A non-zero density of states at the Fermi level is evident from metallic behavior in the normal state, as well as from electronic band structure calculations. The isostructural [Formula: see text] compound is a paramagnet with a moderately enhanced electronic mass, as indicated by the electronic specific heat coefficient [Formula: see text] mJ [Formula: see text] [Formula: see text] and Kadowaki-Woods ratio [Formula: see text] [Formula: see text] [Formula: see text] cm [Formula: see text] [Formula: see text] (mJ)[Formula: see text]. Both [Formula: see text] and [Formula: see text] are crystallographically complex, each hosting 212 atoms per unit cell.

Complex dynamics of droplet traffic in a bifurcating microfluidic channel: periodicity, multistability, and selection rules.

The binary path selection of droplets reaching a T junction is regulated by time-delayed feedback and nonlinear couplings. Such mechanisms result in complex dynamics of droplet partitioning: numerous discrete bifurcations between periodic regimes are observed. We introduce a model based on an approximation that makes this problem tractable. This allows us to derive analytical formulae that predict the occurrence of the bifurcations between consecutive regimes, establish selection rules for the period of a regime, and describe the evolutions of the period and complexity of droplet pattern in a cycle with the key parameters of the system. We discuss the validity and limitations of our model which describes semiquantitatively both numerical simulations and microfluidic experiments.

Prevalence of dental anomalies in a population of cleft lip and palate patients.

OBJECTIVE: The aim of our study was to investigate radiographically the prevalence of dental anomalies in a group of Jordanian cleft lip and/or palate subjects. DESIGN: This is a retrospective review of panoramic radiographs of 78 subjects with cleft lip and/or palate that were evaluated from their file records and investigated for possible dental anomalies. RESULTS: Dental anomalies were found frequently in cleft lip and/or palate subjects. Missing teeth were found in 66.7% of the patients; the tooth most commonly missing was the maxillary lateral incisor. Supernumerary teeth were found in 16.7% of patients; 37% had microdontia; 70.5% had taurodontism; 30.8% had transposition and/or ectopic teeth; 19.2% had dilacerations; and 30.8% had hypoplastic teeth. There was no statistically significant difference in the above anomalies' prevalence between males and females. However, it was found that subjects with bilateral cleft lip and/or palate had significantly more microdontia (p = .005), dilaceration (p = .002), and hypoplastic teeth (p = .0001) than subjects with unilateral cleft lip and/or palate. CONCLUSIONS: The prevalence of dental anomalies in cleft lip and/or palate patients was higher than what had been reported in the normal Jordanian population. This emphasizes the relation of cleft lip and/or palate to all dental anomalies studied. Although our study represents a thorough and complete description of dental anomalies present in a sample of cleft lip and/or palate subjects, larger samples are required to effectively determine the relationship of each dental anomaly with cleft type.

An evidence-based review of CGRP mechanisms in the propagation of chronic visceral pain.

Chronic pain is typically defined as pain that persists after acute tissue damage and inflammation or as pain that follows a chronic disease process and lasts more than three months. Because of its debilitating impact on the quality of life of patients, recent research aims to investigate the mechanisms behind nociception to discover novel therapeutic agents to alleviate pain. One such target is the neuropeptide calcitonin gene-related peptide (CGRP), which has shown to play an integral role in migraine pathophysiology. Effective treatments of migraines with CGRP antagonists have stimulated our efforts toward checking a possible involvement of CGRP in nonheadache pain conditions such as hypertension, congestive heart failure, Alzheimer's disease, and vascular ischemia. Here, we provide a brief overview of chronic pain, with a particular emphasis on the role of CGRP as a fundamental mediator of nociceptive pain as well as a target for novel therapeutic agents.

CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.

Proteolysis mediated by the anaphase-promoting complex (APC) triggers chromosome segregation and exit from mitosis, yet its regulation is poorly understood. The conserved Cdc20 and Cdh1 proteins were identified as limiting, substrate-specific activators of APC-dependent proteolysis. CDC20 was required for the degradation of the APC substrate Pds1 but not for that of other APC substrates, such as Clb2 and Ase1. Conversely, cdh1Delta mutants were impaired in the degradation of Ase1 and Clb2 but not in that of Pds1. Overexpression of either CDC20 or CDH1 was sufficient to induce APC-dependent proteolysis of the appropriate target in stages of the cell cycle in which substrates are normally stable.

Budding yeast Cdc20: a target of the spindle checkpoint.

The spindle checkpoint regulates the cell division cycle by keeping cells with defective spindles from leaving mitosis. In the two-hybrid system, three proteins that are components of the checkpoint, Mad1, Mad2, and Mad3, were shown to interact with Cdc20, a protein required for exit from mitosis. Mad2 and Mad3 coprecipitated with Cdc20 at all stages of the cell cycle. The binding of Mad2 depended on Mad1 and that of Mad3 on Mad1 and Mad2. Overexpression of Cdc20 allowed cells with a depolymerized spindle or damaged DNA to leave mitosis but did not overcome the arrest caused by unreplicated DNA. Mutants in Cdc20 that were resistant to the spindle checkpoint no longer bound Mad proteins, suggesting that Cdc20 is the target of the spindle checkpoint.

Crown morphologic abnormalities in the permanent dentition of patients with cleft lip and palate.

The purpose of this study was to investigate crown morphologic abnormalities in the permanent dentition of subjects with clefts and unaffected controls. This is a prospective study of 100 patients and 60 control subjects. The study was carried out at the Cleft Lip and Palate Center at the King Abdullah University Hospital and at the Maxillofacial Unit at Jordan University of Science and Technology during the period November 2003 to September 2005. Eleven kinds of crown morphology abnormalities commonly described in the permanent dentition were recorded using the Arizona State University Dental Anthropology System. There were 1525 teeth examined in 100 subjects with clefts, and 203 crown morphologic abnormalities were recorded, resulting in a mean of 2 abnormalities per individual. No significant difference between the unilateral and bilateral cleft lip and palate groups was found; however, the difference between the cleft group and the control group was highly significant. Crown morphologic abnormalities were more frequent in the maxillary cleft teeth than in the mandibular teeth and in the anterior teeth than in posterior teeth, with a statistically significant difference. The most frequently found abnormalities in subjects with clefts were peg-shaped maxillary incisors and missing hypocone, followed by excess mammelons. In conclusion, there was a significant increase in the frequency of crown morphologic abnormalities in individuals with clefts when compared with subjects without clefts. Crown morphologic abnormalities occurred throughout the entire dentition and did not follow any predictable pattern.

The spindle checkpoint.

Prior to sister-chromatid separation, the spindle checkpoint inhibits cell-cycle progression in response to a signal generated by mitotic spindle damage or by chromosomes that have not attached to microtubules. Recent work has shown that the spindle checkpoint inhibits cell-cycle progression by direct binding of components of the spindle checkpoint pathway to components of a specialized ubiquitin-conjugating system that is responsible for triggering sister-chromatid separation.

Congenital associated malformations in a sample of Jordanian patients with cleft lip and palate.

PURPOSE: To report the prevalence of associated congenital malformations in Jordanian subjects with oral clefts. PATIENTS AND METHODS: A retrospective study of 196 cleft patients was carried out at the Cleft Centre at King Abdullah University Hospital and Maxillofacial Unit at Jordan University of Science and Technology during the period December 2005 to September 2006. Data were collected by interviewing the parents or patients and reviewing the patient's medical records. RESULTS: Twenty-eight cleft subjects had 44 associated malformations other than cleft. Prevalence of associated congenital malformations in Jordanian cleft patients was 14.3%. Of 44 associated malformations, 20 (45.5%) affected the cardiovascular system (CVS), 7 (15.9%) affected the skeletal system, 6 (13.6%) affected the central nervous system, 4 (9.1%) affected the urogenital system, 4 (9.1%) affected the eyes, 2 (4.5%) affected the ears, and 1 (2.3%) affected the digestive system. Approximately 35.3% of these anomalies affected cleft palate subjects, while 17.4% occurred in bilateral cleft lip with or without cleft palate subjects, and 6.4% affected unilateral cleft lip with or without cleft palate subjects. The most commonly recorded anomaly was atrial septal defect (15.9%). CONCLUSIONS: Increased risk of associated malformations in children with clefts must to be highlighted and disseminated to health professionals involved in the management of children with clefts. Routine screening for other malformation, especially cardiac, skeletal, and central nervous system malformations, may need to be considered in infants with clefts, and genetic counseling seems warranted in most of these complicated cases. There should be a close liaison between the cleft team members to comprehensively cover all aspects of the cleft patient's management.

The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis.

BACKGROUND: In eukaryotic cells, a specialized proteolysis machinery that targets proteins containing destruction-box sequences for degradation and that uses a ubiquitin ligase known as the anaphase-promoting complex/cyclosome (APC) plays a key role in the regulation of mitosis. APC-dependent proteolysis triggers the separation of sister chromatids at the metaphase-anaphase transition and the destruction of mitotic cyclins at the end of mitosis. Recently, two highly conserved WD40-repeat proteins, Cdc20 and Cdh1/Hct1, have been identified as substrate-specific regulators for APC-dependent proteolysis in the budding yeast Saccharomyces cerevisiae. Here, we have investigated the cell cycle regulation of Cdc20 and Cdh1/Hct1. RESULTS: Whereas the levels CDH1/HCT1 RNA and Cdh1/Hct1 protein are constant throughout the cell cycle, CDC20 RNA and Cdc20 protein are present only during late S phase and mitosis and Cdc20 protein is unstable throughout the entire cell cycle. The instability of Cdc20 depends on CDC23 and CDC27, which encode components of the APC. During the G1 phase, a destruction box within Cdc20 mediates its instability, but during S phase and mitosis, although Cdc20 destruction is still dependent on CDC23 and CDC27, it does not depend on the Cdc20 destruction box. CONCLUSIONS: There are remarkable differences in the regulation of Cdc20 and Cdh1/Hct1. Furthermore, the APC activator Cdc20 is itself a substrate of the Cdc27 have a role in the degradation of Cdc20 during S Phase and early mitosis that is not mediated by its destruction box.

Modeling molecular interactions to understand spatial crowding effects on heterodimer formations.

Molecular crowding occurs when the density of interacting molecules in some reaction system is sufficient to create deviations from traditional mass-action models of chemistry in diffusive systems. While there is a great deal of theory on the influence of molecular crowding on biochemistry in vivo, the effects are highly dependent on specific assumptions about the shapes, volumes, and diffusion properties of the components of an individual system and are thus difficult to predict from first principles. In this study, we use lattice Monte Carlo simulations to examine the effects on a reaction system for two limiting cases of the diffusion behavior of inert crowding agents. In cells, inert molecules might diffuse throughout a solute along with the reactant species by passive diffusion or may be anchored at fixed positions within the solute. We investigate the relative contributions of the two models to crowding effects by examining moving inert particles versus stationery inert particles on the kinetics of a heterodimer assembly system. The two models of inert crowding agents resulted in highly divergent effects on the reactant system. Stationary particles exhibited a bimodal response in the reaction rate curve that was a function of copy number and spatial arrangement and which accelerated the process at conditions not unlike those found in cellular environments. On the other hand, moving inert particles created a well mixed background that had no effect on the reaction process even under extremely compacted conditions. These results may have applications in developing more realistic simulations of reaction chemistry in crowded environments such as living cells.

Regulation of the mitotic exit protein kinases Cdc15 and Dbf2.

In budding yeast, the release of the protein phosphatase Cdc14 from its inhibitor Cfi1/Net1 in the nucleolus during anaphase triggers the inactivation of Clb CDKs that leads to exit from mitosis. The mitotic exit pathway controls the association between Cdc14 and Cfi1/Net1. It is comprised of the RAS-like GTP binding protein Tem1, the exchange factor Lte1, the GTPase activating protein complex Bub2-Bfa1/Byr4, and several protein kinases including Cdc15 and Dbf2. Here we investigate the regulation of the protein kinases Dbf2 and Cdc15. We find that Cdc15 is recruited to both spindle pole bodies (SPBs) during anaphase. This recruitment depends on TEM1 but not DBF2 or CDC14 and is inhibited by BUB2. Dbf2 also localizes to SPBs during anaphase, which coincides with activation of Dbf2 kinase activity. Both events depend on the mitotic exit pathway components TEM1 and CDC15. In cells lacking BUB2, Dbf2 localized to SPBs in cell cycle stages other than anaphase and telophase and Dbf2 kinase was prematurely active during metaphase. Our results suggest an order of function of mitotic exit pathway components with respect to SPB localization of Cdc15 and Dbf2 and activation of Dbf2 kinase. BUB2 negatively regulates all 3 events. Loading of Cdc15 on SPBs depends on TEM1, whereas loading of Dbf2 on SPBs and activation of Dbf2 kinase depend on TEM1 and CDC15.