Diabetes Mellitus And The Brain: Special Emphasis To Cognitive Function

Diabetes mellitus (DM) is a major public health problem. Cognitive deficits are common with DM which range from subclinical or subtle to severe deficits as dementia. Both hypoglycemia and hyperglycemia are causes of cognitive impairment with DM. In patients with DM, not only severe hypoglycemia but also recurrent mild or moderate hypoglycemia have deleterious effect on the brain. Recurrent mild/moderate hypoglycemia is associated with intellectual decline, reduced attention, impaired mental abilities and memory deficits. Hypoglycemia may result in abnormalities of neuronal plasticity, synaptic weakening and scattered neuronal death in the cerebral cortex and the hippocampus. Chronic hyperglycemia in type 1 and type 2 DM is associated with low IQ (verbal, performance and total) and abnormalities in testing for different domains of cognitive function as verbal relations, comprehension, visual reasoning, pattern analysis, quantitation, memory, learning, mental control, psychomotor efficiency, mental and motor processing speed and executive function. The suggested mechanisms incriminated in the pathogenesis of hyperglycemia related cognitive dysfunction include, macro- and micro-vascular disease or vasculopathy, hyperlipidemia, hypertension, insulin resistance and hyperinsulinemia, stress response, direct toxic effect of chronic hyperglycemia on the brain, advanced glycation end products, inflammatory cytokines and oxidative stress. Hyperglycemia causes oxidative stress, amyloidosis, angiopathy, abnormal lipid peroxidation, accumulation of β-amyloid and tau phosphorylation, neuroinflammation, mitochondrial pathology, apoptosis and neuronal degeneration in the cortex and hippocampus. Depression has been identified as a risk for accelerated cognitive decline with DM. The knowledge that diagnosis at early age, frequency of hypoglycemia, poor glycemic control and presence of risk factors which negatively affect cognitive functions in DM, will have important implications for treatment and for research purposes

Successful Transplantation of Human Kidneys Deemed Untransplantable but Resuscitated by Ex Vivo Normothermic Machine Perfusion

We report the successful transplantation of a pair of human kidneys that were declined for transplantation due to inadequate in situ perfusion but subsequently transplanted after perfusion and assessment using ex vivo normothermic perfusion (EVNP). The kidneys were from a 35-year-old man, a donation after circulatory death donor. Both kidneys were declined by all UK transplant centers. On arrival, the kidneys had significant areas of incomplete clearance of blood from the microcirculation that did not clear after a further attempt to flush them. Kidneys underwent 60 min of EVNP with an oxygenated packed red blood cell–based solution warmed to 35.2°C. During EVNP, the patchy areas cleared in both kidneys. The mean renal blood flow and total urine output were 68.0 mL/min/100 g and 560 mL in the left kidney and 59.9 mL/min/100 g, 430 mL in the right, respectively. Based on the EVNP perfusion parameters, both kidneys were deemed suitable for transplantation. They were transplanted without any complications, and both recipients had initial graft function. The serum creatinine levels at 3 months were 1.2 mg/dl in the recipient of the left kidney and 1.62 mg/dl in the recipient of the right kidney. EVNP technology can be used to assess and rescue kidneys previously deemed unsuitable for transplantation.This study was supported by Kidney Research UK. The research was also funded by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or NHSBT

الضوابط والتدابير الشرعية في مكافحة الإغراق الاقتصادي: (دراسة فقهية مقارنة بالقانون) Legal controls and measures in the fight against economic dumping (Jurisprudence in compared to the local legislations)

ملخص هدفت الدراسة إلى ضبط حدود الإغراق في صورته المحظورة، وبيان ضوابطه وشروطه، التي تميزه عن غيره من أنواع الإغراق المشروعة من الناحيتين القانونية والشرعية، ومن ثم وضع الحلول والتدابير لمكافحته. وقد تضمنت الدراسة مقدمة وثلاثة مباحث وخاتمة، تناول المبحث الأول: تعريف الإغراق وحكمه الشرعي، وتناول المبحث الثاني: بيان الضوابط والشروط لتجريم الإغراق وتدابير مكافحته من الناحية القانونية، وتناول المبحث الثالث: بيان الضوابط والشروط الشرعية لتجريم الإغراق وتدابير مكافحته في ضوء التشريع الإسلامي، ومقارنة فقهية قانونية لتلك الضوابط والتدابير. وقد خلصت الدراسة إلى أنه لا بد أن تتوافر شروط وضوابط معينة في الإغراق؛ لكي يتوجه إليه المنع والتجريم، منها: تماثل الجودة، والبيع بأقل من السعر الغالب المعتاد، والتسبب بضرر فاحش بطريق قطعي أو بظن غالب، كما قامت الدراسة بحصر وتأصيل التدابير الممكنة لمكافحته والتخفيف من آثاره، منها: الإلزام بسعر السوق، والإخراج منه، والتسعير، والتعويض، وفرض رسوم الإغراق، ودعم المتضررين، والتعزير بالضرب أو الحبس. الكلمات المفتاحية: إغراق، البيع بأقل من سعر السوق، تسعير، سعر السوق، اقتصاد، معاملات مالية معاصرة. Legal controls and measures in the fight against economic dumping (Jurisprudence in compared to the local legislations) Abstract The study aimed at controlling the limits of dumping in its prohibited form, and to clarify its controls and conditions that distinguish it from other types of legitimate dumping in both legal and Sharia terms. It then tried to develop solutions and measures to combat dumbing. The study included an introduction, three topics and a conclusion. The first section dealt with a statement of the origin of dumping and its legal ruling and the second section dealt with a statement of the controls and conditions for criminal dumping and measures to combat it from the legal point of view. The third section dealt with the clarification of the legal controls and conditions for the criminalization of dumping and the measures to combat it in light of Islamic legislation, and a legal jurisprudential for those controls and measures. The study revealed, the prohibition of dumping must be subject to specific conditions and features to be dealt with as illegal or criminal act. From these features: similar quality and sale below the usual prevailing price, causing gross harm in a categorical way or a dominant belief of so. The study also limited and established possible measures to combat and mitigate its effects, including: compulsion at the market price, removal, pricing, compensation, imposition of dumping duties, support for those affected, and the promotion of beatings or imprisonment. Key words: Dumping, selling below market rate, pricing, market value, economy, contemporary financial transactions

Severe axonal neuropathy is a late manifestation of SPG11

Complex hereditary spastic paraplegia (HSP) is a clinically heterogeneous group of disorders usually inherited in an autosomal recessive manner. In the past, complex recessive spastic paraplegias have been frequently associated with SPG11 mutations but also with defects in SPG15, SPG7 and a handful of other rare genes. Pleiotropy exists in HSP genes, exemplified in the recent association of SPG11 mutations with CMT2. In this study, we performed whole exome sequence analysis and identified two siblings with novel compound heterozygous frameshift SPG11 mutations. The mutations segregated with disease were not present in control databases and analysis of skin fibroblast derived mRNA indicated that the SPG11 truncated mRNA species were not degraded significantly by non-sense mediated mRNA decay. These siblings had severe early-onset spastic paraplegia but later in their disease developed severe axonal neuropathy, neuropathic pain and blue/black foot discolouration likely caused by a combination of the severe neuropathy with autonomic dysfunction and peripheral oedema. We also identified a similar late-onset axonal neuropathy in a Cypriot SPG11 family. Although neuropathy is occasionally present in SPG11, in our SPG11 patients reported here it was particularly severe, highlighting the association of axonal neuropathy with SPG11 and the late manifestation of axonal peripheral nerve damage

Distributions of charged massive scalars and fermions from evaporating higher-dimensional black holes

A detailed numerical analysis is performed to obtain the Hawking spectrum for charged, massive brane scalars and fermions on the approximate background of a brane charged rotating higher-dimensional black hole constructed in arXiv:0907.5107. We formulate the problem in terms of a "spinor-like" first order system of differential wave equations not only for fermions, but for scalars as well and integrate it numerically. Flux spectra are presented for non-zero mass, charge and rotation, confirming and extending previous results based on analytic approximations. In particular we describe an inverted charge splitting at low energies, which is not present in four or five dimensions and increases with the number of extra dimensions. This provides another signature of the evaporation of higher-dimensional black holes in TeV scale gravity scenarios.Comment: 19 pages, 6 figures, minor typos corrected, 1 page added with a discussion on higher spins, added reference

Monopoles and Holography

We present a holographic theory in AdS_4 whose zero temperature ground state develops a crystal structure, spontaneously breaking translational symmetry. The crystal is induced by a background magnetic field, but requires no chemical potential. This lattice arises from the existence of 't Hooft-Polyakov monopole solitons in the bulk which condense to form a classical object known as a monopole wall. In the infra-red, the magnetic field is screened and there is an emergent SU(2) global symmetry.Comment: 33 pages, 16 figures; v2: ref adde

Emergent Quantum Near-Criticality from Baryonic Black Branes

We find new black 3-brane solutions describing the "conifold gauge theory" at nonzero temperature and baryonic chemical potential. Of particular interest is the low-temperature limit where we find a new kind of weakly curved near-horizon geometry; it is a warped product AdS_2 x R^3 x T^{1,1} with warp factors that are powers of the logarithm of the AdS radius. Thus, our solution encodes a new type of emergent quantum near-criticality. We carry out some stability checks for our solutions. We also set up a consistent ansatz for baryonic black 2-branes of M-theory that are asymptotic to AdS_4 x Q^{1,1,1}.Comment: 29 pages, 4 figures; v2 discussion of entropy revised, minor changes; v3 note added, minor improvements, version published in JHE

A natural little hierarchy for RS from accidental SUSY

We use supersymmetry to address the little hierarchy problem in Randall-Sundrum models by naturally generating a hierarchy between the IR scale and the electroweak scale. Supersymmetry is broken on the UV brane which triggers the stabilization of the warped extra dimension at an IR scale of order 10 TeV. The Higgs and top quark live near the IR brane whereas light fermion generations are localized towards the UV brane. Supersymmetry breaking causes the first two sparticle generations to decouple, thereby avoiding the supersymmetric flavour and CP problems, while an accidental R-symmetry protects the gaugino mass. The resulting low-energy sparticle spectrum consists of stops, gauginos and Higgsinos which are sufficient to stabilize the little hierarchy between the IR scale and the electroweak scale. Finally, the supersymmetric little hierarchy problem is ameliorated by introducing a singlet Higgs field on the IR brane.Comment: 37 pages, 3 figures; v2: minor corrections, version published in JHE

Emergent Gauge Fields in Holographic Superconductors

Holographic superconductors have been studied so far in the absence of dynamical electromagnetic fields, namely in the limit in which they coincide with holographic superfluids. It is possible, however, to introduce dynamical gauge fields if a Neumann-type boundary condition is imposed on the AdS-boundary. In 3+1 dimensions, the dual theory is a 2+1 dimensional CFT whose spectrum contains a massless gauge field, signaling the emergence of a gauge symmetry. We study the impact of a dynamical gauge field in vortex configurations where it is known to significantly affect the energetics and phase transitions. We calculate the critical magnetic fields H_c1 and H_c2, obtaining that holographic superconductors are of Type II (H_c1 < H_c2). We extend the study to 4+1 dimensions where the gauge field does not appear as an emergent phenomena, but can be introduced, by a proper renormalization, as an external dynamical field. We also compare our predictions with those arising from a Ginzburg-Landau theory and identify the generic properties of Abrikosov vortices in holographic models.Comment: 19 pages, 14 figures, few comments added, version published in JHE

Notes on Operator Equations of Supercurrent Multiplets and the Anomaly Puzzle in Supersymmetric Field Theories

Recently, Komargodski and Seiberg have proposed a new type of supercurrent multiplet which contains the energy-momentum tensor and the supersymmetry current consistently. In this paper we study quantum properties of the supercurrent in renormalizable field theories. We point out that the new supercurrent gives a quite simple resolution to the classic problem, called the anomaly puzzle, that the Adler-Bardeen theorem applied to an R-symmetry current is inconsistent with all order corrections to $\beta$ functions. We propose an operator equation for the supercurrent in all orders of perturbation theory, and then perform several consistency checks of the equation. The operator equation we propose is consisitent with the one proposed by Shifman and Vainshtein, if we take some care in interpreting the meaning of non-conserved currents.Comment: 28 pages; v2:clarifications and references added, some minor change