Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans.

Piwi-interacting RNAs (piRNAs) constitute a class of small RNAs that bind PIWI proteins and are essential to repress transposable elements in the animal germline, thereby promoting genome stability and maintaining fertility. C. elegans piRNAs (21U RNAs) are transcribed individually from minigenes as precursors that require 5' and 3' processing. This process depends on the PETISCO complex, consisting of four proteins: IFE-3, TOFU-6, PID-3, and ERH-2. We used biochemical and structural biology approaches to characterize the PETISCO architecture and its interaction with RNA, together with its effector proteins TOST-1 and PID-1. These two proteins define different PETISCO functions: PID-1 governs 21U processing, whereas TOST-1 links PETISCO to an unknown process essential for early embryogenesis. Here, we show that PETISCO forms an octameric assembly with each subunit present in two copies. Determination of structures of the TOFU-6/PID-3 and PID-3/ERH-2 subcomplexes, supported by in vivo studies of subunit interaction mutants, allows us to propose a model for the formation of the TOFU-6/PID-3/ERH-2 core complex and its functionality in germ cells and early embryos. Using NMR spectroscopy, we demonstrate that TOST-1 and PID-1 bind to a common surface on ERH-2, located opposite its PID-3 binding site, explaining how PETISCO can mediate different cellular roles.

PETISCO is a novel protein complex required for 21U RNA biogenesis and embryonic viability.

Piwi proteins are important for germ cell development in most animals. These proteins are guided to specific targets by small guide RNAs, referred to as piRNAs or 21U RNAs in Caenorhabditis elegans In this organism, even though genetic screens have uncovered 21U RNA biogenesis factors, little is known about how these factors interact or what they do. Based on the previously identified 21U biogenesis factor PID-1 (piRNA-induced silencing-defective 1), we here define a novel protein complex, PETISCO (PID-3, ERH-2, TOFU-6, and IFE-3 small RNA complex), that is required for 21U RNA biogenesis. PETISCO contains both potential 5' cap and 5' phosphate RNA-binding domains and interacts with capped 21U precursor RNA. We resolved the architecture of PETISCO and revealed a second function for PETISCO in embryonic development. This essential function of PETISCO is mediated not by PID-1 but by the novel protein TOST-1 (twenty-one U pathway antagonist). In contrast, TOST-1 is not essential for 21U RNA biogenesis. Both PID-1 and TOST-1 interact directly with ERH-2 using a conserved sequence motif. Finally, our data suggest a role for TOST-1:PETISCO in SL1 homeostasis in the early embryo. Our work describes a key complex for 21U RNA processing in C. elegans and strengthens the view that 21U RNA biogenesis is built on an snRNA-related pathway.

Spherical Shell with CNTs Network Structuring Fe-Based Alluaudite Na2+2 δ Fe2- δ (SO4 )3 Cathode and Novel Phase Transition Mechanism for Sodium-Ion Battery.

Iron-based sulfate cathodes of alluaudite Na2+2 δ Fe2- δ (SO4 )3 (NFS) in sodium-ion batteries with low cost, steady cycling performance, and high voltage are promising for grid-scale energy storage systems. However, the poor electronic conductivity and the limited understanding of the phase-evolution of precursors hinder obtaining high-rate capacity and the pure phase. Distinctive NFS@C@n%CNTs (n = 1, 2, 5, 10) sphere-shell conductive networks composite cathode materials are constructed creatively, which exhibit superior reversible capacity and rate performance. In detail, the designed NFS@C@2%CNTs cathode delivers an initial discharge capacity of 95.9 mAh g-1 at 0.05 C and up to 60 mAh g-1 at a high rate of 10 C. The full NFS@C@2%CNTs//HC cell delivers a practical operating voltage of 3.5 V and mass-energy density of 140 Wh kg-1 at 0.1 C, and it can also retain 67.37 mAh g-1 with a capacity retention rate of 96.4% after 200 cycles at 2 C. On the other hand, a novel combination reaction mechanism is first revealed for forming NFS from the mixtures of Na2 Fe(SO4 )2 ·nH2 O (n = 2, 4) and FeSO4 ·H2 O during the sintering process. The inspiring results would provide a novel perspective to synthesize high-performance alluaudite sulfate and analogs by aqueous methods.

Uncovering the Nonequilibrium Evolution Mechanism between Na2+2 δFe2- δ(SO4)3 Cathode and Impurities in the Na2SO4-FeSO4·7H2O Binary System for High-Voltage Sodium-Ion Batteries.

Sodium-ion batteries are increasingly recognized as ideal for large-scale energy storage applications. Alluaudite Na2+2 δFe2- δ(SO4)3 has become one of the focused cathode materials in this field. However, previous studies employing aqueous-solution synthesis often overlooked the formation mechanism of the impurity phase. In this study, the nonequilibrium evolution mechanism between Na2+2 δFe2- δ(SO4)3 and impurities by adjusting ratios of the Na2SO4/FeSO4·7H2O in the binary system is investigated. Then an optimal ratio of 0.765 with reduced impurity content is confirmed. Compared to the poor electrochemical performance of the Na2.6Fe1.7(SO4)3 (0.765) cathode, the optimized Na2.6Fe1.7(SO4)3@CNTs (0.765@CNTs) cathode, with improved electronic and ionic conductivity, demonstrates an impressive discharge specific capacity of 93.8 mAh g-1 at 0.1 C and a high-rate capacity of 67.84 mAh g-1 at 20 C, maintaining capacity retention of 71.1% after 3000 cycles at 10 C. The Na2.6Fe1.7(SO4)3@CNTs//HC full cell reaches an unprecedented working potential of 3.71 V at 0.1 C, and a remarkable mass-energy density exceeding 320 Wh kg-1. This work not only provides comprehensive guidance for synthesizing high-voltage Na2+2 δFe2- δ(SO4)3 cathode materials with controllable impurity content but also lays the groundwork of sodium-ion batteries for large-scale energy storage applications.

Biomass Carbon Dots as Fluorescent Probes for Fast and Highly Selective Detection of Fe3 + in Water Media.

In this study, a novel fluorescent probe for the rapid and highly selective detection of Fe3 + based on biomass carbon dots (b-CDs) was developed. The b-CDs were obtained via one-step hydrothermal synthesis by utilizing laurel fallen leaves. And the as-synthesized b-CDs were applied for sensing Fe3+ based on fluorescence (FL) quenching effect both in water and phosphate buffer solution (PBS) with a wide linear range from 1 µM to 300 µM, the detection limits (LODs) respectively to be 0.34 µM in water and 0.48 µM in PBS solution. The FL intensity of b-CDs was quenched fleetly within 1 min after adding Fe3+. The sensing mechanism of the b-CDs + Fe3+ system can be attributed to the internal filtration effect (IFE) mechanism and the electron transfer (ET) between b-CDs and Fe3+ in water, and only the IFE mechanism in PBS solution based on multiple experimental evidences. Moreover, the as-proposed probe was successfully adopted for monitoring Fe3+ in lake water and tap water samples. This research shows some merits of economic, simplicity, green, high selectivity, and quick response for Fe3+ determination, and provides an approach for the water quality monitoring of Fe3+ and the effective utilization of waste biological materials.

Microwave Synthesis of Fluorescent Carbon Quantum dots from Araucaria Heterophylla Gum: Application in Drug Detection.

This study employed a green microwave synthesis technique to produce carbon quantum dots (CQDs) from araucaria heterophylla gum extract. The produced CQDs emit a distinct blue fluorescent light, contributing a remarkable quantum yield of 14.69%. Their average particle size measures at 1.62 ± 0.39 nm. Furthermore, these CQDs demonstrate excellent water solubility and maintain high fluorescence stability despite ionic strength, pH and time variations. Moreover, we present here for the first time that the synthesized CQDs demonstrate a rapid, exceptionally sensitive, and discerning fluorescence quenching phenomenon (IFE) concerning Cefprozil (CPR). The fluorescent probe was sensitive and specific with good linear relationships for CPR in the 0-18 µM range. The limit of detection for relationships for CPR was 2.51 µM. This study provides novel opportunities for producing high-quality luminescent CQDs that meet the requirements for various biological and environmental applications.

Self-assembly of S,N-codoped Ce/Cu bimetallic nanoparticles for fluorescence and visual detection of hexavalent chromium.

Ce2(SO4)3 was doped into 4,6-diamino-2-mercaptopyrimidine (DAMP)-encapsulated copper nanoclusters (CuNCs) via a facile, rapid, low-temperature, and green self-assembly synthesis method to obtain fluorescent S,N-codoped Cu/Ce-DAMP nanoparticles (S,N-codoped Cu/CeNPs) for the detection of Cr(VI). The prepared Cu/CeNPs exhibit double emission peaks at 470 nm and 610 nm. The fluorescence emission at 610 nm is significantly enhanced due to the aggregation-induced emission (AIE) effect, and the quantum yield is as high as 20.19%. The fluorescence emission at 610 nm can be selectively quenched by Cr(VI) due to the internal filter effect (IFE) and dynamic quenching, whereas the weak fluorescence at 470 nm remains almost stable. On this basis, a fluorescence assay method for Cr(VI) was established, with good linearity in the concentration range 0.5-120 µM and a detection limit (LOD) of 134 nM. Using a smartphone to take photos of the fluorescence signals changes caused by Cr(VI) rapid visual detection is achieved with a linear range of 10-130 µM and a LOD of 2.35 µM. The proposed method was successfully applied to the detection of Cr(VI) in actual water samples.

Single Step Solid State Synthesis of Carbon Nanoparticles for Instantaneous Detection of Fe (III) in Water Samples.

Though iron is one of the vital micronutrients in biological systems excess of which is associated with various illness. Consumption of contaminated water and crops because of its extensive industrial utility is one of the major sources for excess iron in living beings. Hence, we have designed a sensor based on carbon nanoparticles for the detection of Fe (III) and we have also attempted to estimate Fe (III) in spiked water samples. Carbon nanoparticles (CNP) with quantum yield of 40.2 % was synthesized by solid state synthesis from aromatic molecular precursors unlike conventional synthesis methodology. The particle size, stability and optical properties of CNP were investigated by microscopic and spectroscopic techniques. CNP manifested a naked color change from colorless to yellow in presence of Fe (III) and 72 % of CNP's emission was quenched at 487 nm on excitation at 377 nm by Fe (III). The detection time was less than a second and limit of detection was calculated as 0.248 µM. The mechanistic aspect of detection was investigated and applicability of CNP was examined in spiked water samples.

EDA-NOCV analysis of carbene-borylene bonded dinitrogen complexes for deeper bonding insight: A fair comparison with a metal-dinitrogen system.

Binding of dinitrogen (N2 ) to a transition metal center (M) and followed by its activation under milder conditions is no longer impossible; rather, it is routinely studied in laboratories by transition metal complexes. In contrast, binding of N2 by main group elements has been a challenge for decades, until very recently, an exotic cAAC-borylene (cAAC = cyclic alkyl(amino) carbene) species showed similar binding affinity to kinetically inert and non-polar dinitrogen (N2 ) gas under ambient conditions. Since then, N2 binding by short lived borylene species has made a captivating news in different journals for its unusual features and future prospects. Herein, we carried out different types of DFT calculations, including EDA-NOCV analysis of the relevant cAAC-boron-dinitrogen complexes and their precursors, to shed light on the deeper insight of the bonding secret (EDA-NOCV = energy decomposition analysis coupled with natural orbital for chemical valence). The hidden bonding aspects have been uncovered and are presented in details. Additionally, similar calculations have been carried out in comparison with a selected stable dinitrogen bridged-diiron(I) complex. Singlet cAAC ligand is known to be an exotic stable species which, combined with the BAr group, produces an intermediate singlet electron-deficient (cAAC)(BAr) species possessing a high lying HOMO suitable for overlapping with the high lying π*-orbital of N2 via effective π-backdonation. The BN2 interaction energy has been compared with that of the FeN2 bond. Our thorough bonding analysis might answer the unasked questions of experimental chemists about how boron compounds could mimic the transition metal of dinitrogen binding and activation, uncovering hidden bonding aspects. Importantly, Pauling repulsion energy also plays a crucial role and decides the binding efficiency in terms of intrinsic interaction energy between the boron-center and the N2 ligand.

Reuse of waste Myrica rubra for green synthesis of nitrogen-doped carbon dots as an "on-off-on" fluorescent probe for Fe3+ and ascorbic acid detection.

As one kind of high nutrition fruits, abandoned Myrica rubra causes great waste due to short storage period. For resource utilization, we herein fabricated the Myrica rubra-based N-doped carbon dots (MN-CDs) by a facile/green hydrothermal method. MN-CDs, fabricated from four regions of China, displayed significant differences in their corresponding fluorescence intensities (FIs). Interestingly, different batches of waxberry samples from the same region (Wenzhou, China) exhibited slight differences in their FIs, and also an excellent anti-photobleaching and anti-salt capacity. Based on Fe3+-triggered quenching effect and fluorescent recovery by redox reaction of AA and Fe3+, MN-CDs were employed to construct an "on-off-on" switch probe for sequential detection of Fe3+ and ascorbic acid (AA). Through Zeta potential, UV spectrum, Stern-Volmer equation, and valence-conduction band theory, the Fe3+-triggered quenching belonged to a static quenching process, which resulted from the synergistic contribution of inner filtering effect and photo-induced electron transfer mechanisms. The linear ranges for Fe3+ and AA detections were 1-1000 and 0.1-1000 mM. The limits of detection were 0.3 µM for Fe3+ in environmental waters, and 0.03 µM for AA in pharmaceutical tablets and fruit juice samples. Under 365-nm UV lamp, the color changes of test papers were easily observed from dark blue and bright blue in the presence of Fe3+ and AA, and thus the MN-CDs-based switch probe could be satisfactorily used for visually qualitative detection of Fe3+ and AA outdoor with our naked eyes. To sum up, MN-CDs not only realize resource reutilization of abandoned Myrica rubra, but also offer an convenient outdoor approach for qualitative detection of Fe3+ and AA in complex matrices.

A ratiometric fluorescence strategy based on copper nanoclusters/carbon dots for sensitive detection of doxorubicin.

Sensitive detection of doxorubicin (DOX) is critical for clinical theranostics. A novel ratiometric fluorescence strategy based on the inner filter effect (IFE) has been established for the sensitive detection of DOX by designing a ratiometric fluorescence probe. In the presence of DOX, the fluorescence intensity of copper nanoclusters (CuNCs) at 485 nm decreases, and the fluorescence intensity of carbon dots at 560 nm increases. Therefore, DOX can be quantitatively detected by measuring the ratio of the fluorescence intensities at 560 and 485 nm (F560 /F485 ). The F560 /F485 ratio exhibits a linear correlation with the DOX concentration in the range from 1.0 × 10-8 M to 1.0 × 10-4 M with the detection limit of 3.7 nM. Furthermore, this method was also successfully applied to the analysis of DOX in human plasma samples, affording an effective platform for drug safety management.

Evaluation of physicochemical properties and heavy metal speciation of groundwater in Ifetedo and Garage Olode, Osun State, Nigeria.

To a large extent, public health can be prevented from being compromised by having access to potable water whose physicochemical fingerprints conform to the WHO Guidelines for drinking water. This study was carried out to assess the physicochemical properties and heavy metals speciation of groundwater in Nigeria. Water samples from thirteen sites were collected for three months and analysed for levels of pH, conductivity, nitrate, sulphate, phosphate, and heavy metals using standard methods. The results of the analysis revealed that the respective mean temperature, conductivity, pH, total dissolved solids, and oxygen reduction potential of Ifetedo sites were 27.57 ± 0.66 °C, 318.93 ± 108.58 µS/cm, 5.29 ± 0.20, 207.40 ± 73.58 mg/L, and 265.17 ± 11.29 mV, while those of Garage Olode were 28.53 °C, 275.04 ± 133.75 µS/cm, 5.23 ± 0.04, 177.66 ± 89.37 mg/L, and 270.43 ± 37.75 mV. Total mean levels (µg/mL) of heavy metals ranged from 0.04 ± 0.01 Cd to 26.21 ± 3.63 Mn at Ifetedo, while at Garage Olode, the range was between 0.02 ± 0.00 Cd and 14.49 ± 5.70 Mn. The respective ranges of mean values (µg/mL) of exchangeable metals were 0.01 ± 0.00 Cd to 10.64 ± 1.20 Mn and 0.01 ± 0.00 to 7.53 ± 2.57 Mn at Ifetedo and Garage Olode. Going by WHO provision for drinking water, the study concluded that the levels of heavy metals in the potable water samples could constitute serious health hazards over prolonged usage unless some water treatment protocols are adopted.

Preparations for a European R&D roadmap for an inertial fusion demo reactor.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

"Turn on" Fluorescence Sensor of Glutathione Based on Inner Filter Effect of Co-Doped Carbon Dot/Gold Nanoparticle Composites.

Glutathione (GSH) is a thiol that plays a significant role in nutrient metabolism, antioxidant defense and the regulation of cellular events. GSH deficiency is related to variety of diseases, so it is useful to develop novel approaches for GSH evaluation and detection. In this study we used nitrogen and phosphorus co-doped carbon dot-gold nanoparticle (NPCD-AuNP) composites to fabricate a simple and selective fluorescence sensor for GSH detection. We employed the reductant potential of the nitrogen and phosphorus co-doped carbon dots (NPCDs) themselves to form AuNPs, and subsequently NPCD-AuNP composites from Au3+. The composites were characterized by using a range of spectroscopic and electron microscopic techniques, including electrophoretic light scattering and X-ray diffraction. The overlap of the fluorescence emission spectrum of NPCDs and the absorption spectrum of AuNPs resulted in an effective inner filter effect (IFE) in the composite material, leading to a quenching of the fluorescence intensity. In the presence of GSH, the fluorescence intensity of the composite was recovered, which increased proportionally to increasing the GSH concentration. In addition, our GSH sensing method showed good selectivity and sensing potential in human serum with a limit of detection of 0.1 µM and acceptable results.

Audit of the Prevalence of Noncorrelation of Immunofixation with Protein Electrophoresis and Serum Free Light Chain Assays in Multiple Myeloma in a Tertiary Cancer Care Center.

Multiple myeloma (MM) is diagnosed and monitored by correlating panel of test results including serum Protein electrophoresis (SPE), Immunofixation electrophoresis (IFE), serum Free Light chain (sFLC) measurements. This audit is aimed to evaluate the prevalence of non-correlation and discrepancies amongst the three investigations (SPE/IFE/sFLC) for assessment of MM. 106 MM patients were reviewed over 16 months in a tertiary cancer care center by the availability of 3 serum test results (SPE/IFE/sFLC). Patients were divided into 2 groups: group1, newly diagnosed MM patients who were yet to receive myeloma specific treatment (n = 48); and group2, already diagnosed MM patients on treatment and followup (n = 58). Treatment modalities included stem cell transplantation and standard chemotherapy regimens. Non-correlation between the three test results (IFE/SPE/sFLC) was observed (21% in group1 and 45% in group2). Three types of discrepancies were detected as follows: (a) IFE showing less number of restriction bands as compared to SPE (8.6% patients in group2); (b) SPE/IFE negative with an abnormal sFLC ratio (12.5% patients in group1 and 13.7% in group2); (c) SPE/IFE positive but normal sFLC ratio (8% in group1 and 22% in group2). To conclude, IFE may sometimes provide information that does not always correlate with either of the SPE or sFLC results due to different sensitivities, antigen-antibody interactions, or treatment. Hence, SPE plus sFLC may be more useful particularly for patients on follow-up while IFE plus sFLC may help screen the new patients. The judicious selection of the biochemical assays can effectively reduce the treatment cost in a developing country like India.

Study on Quantitative Analysis of Carbon and Nitrogen in Stoichiometric θ-Fe3C and γ'-Fe4N by Atom Probe Tomography.

The quantitative analysis performance of carbon and nitrogen was investigated using stoichiometric θ-Fe3C (25 at% C) and γ'-Fe4N (~20 at% N) precipitates in pulsed voltage and pulsed laser atom probes. The dependencies of specimen temperature, pulse fraction, and laser pulse energy on the apparent concentrations of carbon and nitrogen were measured. Good coincidence with 25 at% carbon concentration in θ-Fe3C was obtained for the pulsed voltage atom probe by considering the mean number of carbon atoms per ion at 24 Da and the detection loss of iron, while better coincidence was obtained for the pulsed laser atom probe by considering only the mean number of carbon at 24 Da. On the other hand, a lack of nitrogen concentration in γ'-Fe4N was observed for the two atom probes. In particular, the pulsed laser atom probe showed a significant lack of nitrogen concentration. This implies that a large amount of 14N2+ was obscured by the main iron peak of 56Fe2+ at 28 Da in the mass-to-charge spectrum. Regarding preferential evaporation or retention, carbon in θ-Fe3C exhibited little of either, but nitrogen in γ'-Fe4N exhibited definite preferential retention. This result can be explained by the large difference in ionization energy between carbon and nitrogen.

Green emitting carbon dots for sensitive fluorometric determination of cartap based on its aggregation effect on gold nanoparticles.

A fluorometric method was developed for the determination of the insecticide cartap. It is based on the use of green emitting carbon dots (CDs) and gold nanoparticles (Au NPs). The CDs were prepared from phenol and ethylene diamine by a hydrothermal route. They have excitation/emission maxima at 410/513 nm) and a fluorescence quantum yield of 29%. They were characterized by TEM, Raman, XRD, XPS, FT-IR, UV and fluorescence spectroscopies. The green fluorescence of the CDs is strongly reduced by the red-colored Au NPs because of an inner filter effect. Upon addition of cartap, it will cause the aggregation of the Au NPs owing to Au-N interaction between Au NPs and cartap to form purple colored aggregates with spectra that do not overlap the green emission of the CDs. Hence, their fluorescence is restored. Under optimum conditions, the method allows for the quantitation of cartap in the 5-300 nM concentration range, and the detection limit is 3.8 nM. The method was successfully applied to the determination of cartap in spiked real samples and gave satisfactory results. Graphical abstract Schematic presentation of green emitting carbon dots for sensitive fluorometric determination of cartap based on its aggregation effect on gold nanoparticles.

Sensitively and Selectively Detect Biothiols by Using Fluorescence Method and Resonance Light Scattering Technique Simultaneously.

In this paper, we designed a new quantitative and qualitive detection method for biothiols by using fluorescence method and resonance light scattering (RLS) technique. Nitrogen doped carbon quantum dots (C/N-dots) were obtained from tartaric acid and ethylenediamine by hydrothermal method, and then their morphology and optical properties were characterized by different techniques. A detection system consisting of C/N-dots and Ag+ complex was established. In this system, C/N-dots possessed the photoluminescent property and the Ag+ complex owned the RLS property, so, by combining the two luminescent properties to achieve complementary advantages, we could detect biothiols and solve the problem of distinguishing between Cys and GSH. Additionally, we optimized detecting conditions and investigated the detection mechanism of fluorescence quenching and RLS detecting. Results showed that the analytical response of fluorescence was linear in the range 0-140 µM and the detection limit (LOD) was calculated to be 6.6 µM for Cys, and the addition of GSH had no effect on fluorescence. RLS response ranges were 0-167 µM for Cys and 0-200 µM for GSH, with LOD down to 64 nM and 74 nM, respectively. Furthermore, the probe was successfully used for detecting Cys in fetal bovine serum (FBS) samples by fluorescence method, and also, by RLS technique, the content of GSH in FBS samples was detected.

The distribution and pattern of neurological disease in a neurology clinic in Ile-Ife, Nigeria.

BACKGROUND: Neurological disorders are common and contribute significantly to disease burden, disability-adjusted life years and death. OBJECTIVE: To assess the distribution of neurological disease in patients presenting to our hospital. METHODS: The records of the Adult Neurology Clinic in Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun state, Nigeria were reviewed retrospectively for the years 2003-2005 and 2010-2014, and diagnoses as made by the Consultant were obtained and analyzed. RESULTS: The total number of complaints was 1,524 and 86.4% of these were neurological in nature. Episodic and paroxysmal disorders (ICD-10) accounted for 54.1% of the diagnoses, and epilepsy and stroke were the most common of these. Of the 1,226 patients seen during the period, 91.4% had neurological disorders. The peak occurrence of these disorders was within the first three decades of life. CONCLUSION: Epilepsy and stroke are the commonest neurological disorders in the outpatient setting and there should be more studies in the community on their prevalence and impact.

Long-Lived Epidermal Cancer-Initiating Cells.

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population, as well as an economic load to the health care system; yet treatments of these preventable cancers remain ineffective. Studies estimate that there has been a 2-fold increase in the incidence of NMSCs between the 1960s and 1980s. The increase in cases of NMSCs, as well as the lack of effective treatments, makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgently required. Research over the past few years has provided data supporting both a "bottom up" and "top down" mechanism of tumourigenesis. The "bottom up" concept involves a cancer stem cell originating in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. The "top down" concept involves a more differentiated cell undergoing genetic modifications leading to dedifferentiation, giving rise to cancer initiating cells (CICs). This review explores both concepts, to paint a picture of the skin SCC cell of origin, the underlying biology, and also how this knowledge might be exploited to develop novel therapies.