Miracle-dz/UniFAR-FTUs huggingface dataset:
Ambulatory Epigastric Hernia Repair Using Local Anaesthesia: A Pragmatic Approach In A Resource Poor Society

E.A. Agbakwuru1; A.C. Etonyeaku1, A.A. Akinkuolie1, A.O. Talabi1, O. Olasehinde1, A. Olekwu2, A. Ojo3, I.O. Akingbade4. 1Department of Surgery, Obafemi Awolowo Teaching Hospital Complex, Wesley Guilds Hospital Unit, Ilesa, Osun state, Nigeria. 2Department of Surgery Federal Medical Centre, Owo Ondo state, Nigeria. 3Department of Anaethesia, Obafemi Awolowo Teaching Hospital Complex, Wesley Guilds Hospital Unit, Ilesa, Osun state, Nigeria. 4Department of Anaethesia, Federal Medical Centre, Owo Ondo state, Nigeria. Correspondence to: Etonyeaku, Amarachukwu C, Email: dretonyeaku@gmail.com
Evidence for the Co‐Expression of Oxytocin and Vasopressin Messenger Ribonucleic Acids in Magnocellular Neurosecretory Cells: Simultaneous Demonstration of Two Neurohypophysin Messenger Ribonucleic Acids by Hybridization Histochemistry

A novel enzyme‐labelled oligonucleotide probe specific for oxytocin messenger ribonucleic acid (mRNA) and a radiolabelled oligonucleotide probe specific for vasopressin mRNA were used together to visualize both oxytocin and vasopressin mRNA's in hypothalamus sections from salt loaded (2% saline) rats. The results demonstrate that the majority of magnocellular neurons contain only oxytocin or vasopressin mRNA, however a small number of neurons, 1% to 2%, contained both oxytocin and vasopressin transcripts.
Dopamine deficiency underlies learning deficits in neurofibromatosis‐1 mice

Children with neurofibromatosis type 1 (NF1) are prone to learning and behavioral abnormalities, including problems with spatial learning and attention. The molecular etiology for these deficits is unclear, as previous studies have implicated defective dopamine, cyclic adenosine monophosphate (cAMP), and Ras homeostasis. Using behavioral, electrophysiological, and primary culture, we now demonstrate that reduced dopamine signaling is responsible for cAMP‐dependent defects in neuron function and learning. Collectively, these results establish defective dopaminergic function as a contributing factor underlying impaired spatial learning and memory in children and adults with NF1, and support the use of treatments that restore normal dopamine homeostasis for select individuals. ANN NEUROL 2013;73:309–315
Neue Serumeisenbestimmung auf dem GSA II

The method for the determination of serum iron using guanidine hydrochloride-FerroZine was adapted to the Greiner Selective Analyzer II. Possible interferences and the reference values were determined. Disturbances may be due to hemoglobin (200 mg/dl) and substances which form iron complexes such as EDTA · Na2 (10 mg/dl) andDesferal (140mg/dl). The influence of copper can be neglected under routine conditions.
p53 Protein-mediated Up-regulation of MAP Kinase Phosphatase 3 (MKP-3) Contributes to the Establishment of the Cellular Senescent Phenotype through Dephosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2)*

Background: Growth arrest is a hallmark of cellular senescence. Results: Loss of cell proliferation in senescent cells was associated with impaired ERK1/2 activation, which was caused by p53-mediated elevation of MKP-3. Conclusion: The p53/MKP-3/ERK1/2 cascade contributed to the establishment of the senescent phenotype. Significance: Our study provides novel insights into the actions and mechanisms of p53 on cellular senescence. Growth arrest is one of the essential features of cellular senescence. At present, the precise mechanisms responsible for the establishment of the senescence-associated arrested phenotype are still incompletely understood. Given that ERK1/2 is one of the major kinases controlling cell growth and proliferation, we examined the possible implication of ERK1/2. Exposure of normal rat epithelial cells to etoposide caused cellular senescence, as manifested by enlarged cell size, a flattened cell body, reduced cell proliferation, enhanced β-galactosidase activity, and elevated p53 and p21. Senescent cells displayed a blunted response to growth factor-induced cell proliferation, which was preceded by impaired ERK1/2 activation. Further analysis revealed that senescent cells expressed a significantly higher level of mitogen-activated protein phosphatase 3 (MKP-3, a cytosolic ERK1/2-targeted phosphatase), which was suppressed by blocking the transcriptional activity of the tumor suppressor p53 with pifithrin-α. Inhibition of MKP-3 activity with a specific inhibitor or siRNA enhanced basal ERK1/2 phosphorylation and promoted cell proliferation. Apart from its role in growth arrest, impairment of ERK1/2 also contributed to the resistance of senescent cells to oxidant-elicited cell injury. These results therefore indicate that p53-mediated up-regulation of MKP-3 contributes to the establishment of the senescent cellular phenotype through dephosphorylating ERK1/2. Impairment of ERK1/2 activation could be an important mechanism by which p53 controls cellular senescence.
Functional Consequences of Glucagon-like Peptide-1 Receptor Cross-talk and Trafficking*

Background: Receptor trafficking and cross-talk regulate 7TM/GPCR signaling capacity. Results: Inhibition of GLP-1R internalization in the presence of GIPR reduces GLP-1R signaling. Conclusion: GLP-1R internalization is essential for full receptor functionality and is abrogated upon cross-talk with GIPR. Significance: GLP-1R cross-talk with GIPR has functional consequences for GLP-1R signaling. The signaling capacity of seven-transmembrane/G-protein-coupled receptors (7TM/GPCRs) can be regulated through ligand-mediated receptor trafficking. Classically, the recycling of internalized receptors is associated with resensitization, whereas receptor degradation terminates signaling. We have shown previously that the incretin glucagon-like peptide-1 receptor (GLP-1R) internalizes fast and is primarily resensitized through recycling back to the cell surface. GLP-1R is expressed in pancreatic islets together with the closely related glucose-dependent insulinotropic polypeptide (GIPR) and glucagon (GCGR) receptors. The interaction and cross-talk between coexpressed receptors is a wide phenomenon of the 7TM/GPCR superfamily. Numerous reports show functional consequences for signaling and trafficking of the involved receptors. On the basis of the high structural similarity and tissue coexpression, we here investigated the potential cross-talk between GLP-1R and GIPR or GCGR in both trafficking and signaling pathways. Using a real-time time-resolved FRET-based internalization assay, we show that GLP-1R, GIPR, and GCGR internalize with differential properties. Remarkably, upon coexpression of the internalizing GLP-1R and the non-internalizing GIPR, GLP-1-mediated GLP-1R internalization was impaired in a GIPR concentration-dependent manner. As a functional consequence of such impaired internalization capability, GLP-1-mediated GLP-1R signaling was abrogated. A similar compromised signaling was found when GLP-1R internalization was abrogated by a dominant-negative version of dynamin (dynamin-1 K44E), which provides a mechanistic link between GLP-1R trafficking and signaling. This study highlights the importance of receptor internalization for full functionality of GLP-1R. Moreover, cross-talk between the two incretin receptors GLP-1R and GIPR is shown to alter receptor trafficking with functional consequences for GLP-1R signaling.
Molecular Mechanisms of Calcium-sensing Receptor-mediated Calcium Signaling in the Modulation of Epithelial Ion Transport and Bicarbonate Secretion*

Background: Calcium-sensing receptor (CaSR) plays a critical role in the regulation of epithelial ion transport. Results: CaSR activators induce Ca2+ signaling and duodenal bicarbonate secretion (DBS). Conclusion: CaSR triggers Ca2+-dependent DBS, likely through receptor-operated channels, intermediate conductance Ca2+-activated K+ channels, and the cystic fibrosis transmembrane conductance regulator. Significance: Dietary CaSR activators may modulate the physiological process of DBS that is critical for duodenal mucosal protection. Epithelial ion transport is mainly under the control of intracellular cAMP and Ca2+ signaling. Although the molecular mechanisms of cAMP-induced epithelial ion secretion are well defined, those induced by Ca2+ signaling remain poorly understood. Because calcium-sensing receptor (CaSR) activation results in an increase in cytosolic Ca2+ ([Ca2+]cyt) but a decrease in cAMP levels, it is a suitable receptor for elucidating the mechanisms of [Ca2+]cyt-mediated epithelial ion transport and duodenal bicarbonate secretion (DBS). CaSR proteins have been detected in mouse duodenal mucosae and human intestinal epithelial cells. Spermine and Gd3+, two CaSR activators, markedly stimulated DBS without altering duodenal short circuit currents in wild-type mice but did not affect DBS and duodenal short circuit currents in cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice. Clotrimazole, a selective blocker of intermediate conductance Ca2+-activated K+ channels but not chromanol 293B, a selective blocker of cAMP-activated K+ channels (KCNQ1), significantly inhibited CaSR activator-induced DBS, which was similar in wild-type and KCNQ1 knockout mice. HCO3− fluxes across epithelial cells were activated by a CFTR activator, but blocked by a CFTR inhibitor. CaSR activators induced HCO3− fluxes, which were inhibited by a receptor-operated channel (ROC) blocker. Moreover, CaSR activators dose-dependently raised cellular [Ca2+]cyt, which was abolished in Ca2+-free solutions and inhibited markedly by selective CaSR antagonist calhex 231, and ROC blocker in both animal and human intestinal epithelial cells. Taken together, CaSR activation triggers Ca2+-dependent DBS, likely through the ROC, intermediate conductance Ca2+-activated K+ channels, and CFTR channels. This study not only reveals that [Ca2+]cyt signaling is critical to modulate DBS but also provides novel insights into the molecular mechanisms of CaSR-mediated Ca2+-induced DBS.
A Distinct Switch in Interactions of the Histone H4 Tail Domain upon Salt-dependent Folding of Nucleosome Arrays*

Background: The core histone tail domains are essential for formation of native chromatin structures, but interactions are poorly understood. Results: H4 tail-DNA intra-nucleosome contacts are lost upon nucleosome array condensation, but intra-array, inter-nucleosome DNA contacts are not detected. Conclusion: The multiple functions of the H4 tail require targeted distinct interactions within condensed chromatin. Significance: These results illuminate how the H4 tail stabilizes higher-order chromatin structures. The core histone tail domains mediate inter-nucleosomal interactions that direct folding and condensation of nucleosome arrays into higher-order chromatin structures. The histone H4 tail domain facilitates inter-array interactions by contacting both the H2A/H2B acidic patch and DNA of neighboring nucleosomes (1, 2). Likewise, H4 tail-H2A contacts stabilize array folding (3). However, whether the H4 tail domains stabilize array folding via inter-nucleosomal interactions with the DNA of neighboring nucleosomes remains unclear. We utilized defined oligonucleosome arrays containing a single specialized nucleosome with a photo-inducible cross-linker in the N terminus of the H4 tail to characterize these interactions. We observed that the H4 tail participates exclusively in intra-array interactions with DNA in unfolded arrays. These interactions are diminished during array folding, yet no inter-nucleosome, intra-array H4 tail-DNA contacts are observed in condensed chromatin. However, we document contacts between the N terminus of the H4 tail and H2A. Installation of acetylation mimics known to disrupt H4-H2A surface interactions did not increase observance of H4-DNA inter-nucleosomal interactions. These results suggest the multiple functions of the H4 tail require targeted distinct interactions within condensed chromatin.
Linking MRI postprocessing with magnetic source imaging in MRI‐negative epilepsy

MRI‐negative (MRI–) pharmacoresistant focal epilepsy (PFE) patients are most challenging for epilepsy surgical management. This study utilizes a voxel‐based MRI postprocessing technique, implemented using a morphometric analysis program (MAP), aiming to facilitate detection of subtle focal cortical dysplasia (FCD) in MRI– patients. Furthermore, the study examines the concordance between MAP‐identified regions and localization from magnetic source imaging (MSI).
Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease

We have described cerebrospinal fluid (CSF) myeloid microvesicles (MVs) as a marker of microglia activation during neuroinflammation in Alzheimer disease (AD), and characterized their ability to produce toxic amyloid β1–42 (Aβ1–42) oligomers from aggregated or soluble substrate. The aim of this study is to investigate the association of CSF myeloid MVs with neuroimaging, clinical, and paraclinical data in AD and mild cognitive impairment (MCI).
HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor*

Background: The transcription factor IRF3 is not properly activated during HIV-1 infection. Results: Infection with VSV-G-pseudotyped HIV-1 induces caspase-mediated cleavage of IRF3, and Vpu contributes to this event. Conclusion: The product of IRF3 cleavage by HIV-1 interferes with IRF3-regulated gene expression. Significance: Our findings contribute to the understanding of how HIV-1 attenuates the innate anti-viral response. Vpu is an accessory protein encoded by HIV-1 that interferes with multiple host-cell functions. Herein we report that expression of Vpu by transfection into 293T cells causes partial proteolytic cleavage of interferon regulatory factor 3 (IRF3), a key transcription factor in the innate anti-viral response. Vpu-induced IRF3 cleavage is mediated by caspases and occurs mainly at Asp-121. Cleavage produces a C-terminal fragment of ∼37 kDa that comprises the IRF dimerization and transactivation domains but lacks the DNA-binding domain. A similar cleavage is observed upon infection of the Jurkat T-cell line with vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped HIV-1. Two other HIV-1 accessory proteins, Vif and Vpr, also contribute to the induction of IRF3 cleavage in both the transfection and the infection systems. The C-terminal IRF3 fragment interferes with the transcriptional activity of full-length IRF3. Cleavage of IRF3 under all of these conditions correlates with cleavage of poly(ADP-ribose) polymerase, an indicator of apoptosis. We conclude that Vpu contributes to the attenuation of the anti-viral response by partial inactivation of IRF3 while host cells undergo apoptosis.
Autophagy Enhances Intestinal Epithelial Tight Junction Barrier Function by Targeting Claudin-2 Protein Degradation*

Background: How autophagy, a cell survival mechanism, regulates intestinal epithelial tight junction barrier or paracellular permeability is unknown. Results: Autophagy reduces the paracellular permeability of small solutes and ions via degradation of the pore-forming tight junction protein claudin-2. Conclusion: Autophagy enhances tight junction barrier function by targeting claudin-2. Significance: This is the first report showing autophagy regulation of the intestinal tight junction barrier. Autophagy is an intracellular degradation pathway and is considered to be an essential cell survival mechanism. Defects in autophagy are implicated in many pathological processes, including inflammatory bowel disease. Among the innate defense mechanisms of intestinal mucosa, a defective tight junction (TJ) barrier has been postulated as a key pathogenic factor in the causation and progression of inflammatory bowel disease by allowing increased antigenic permeation. The cross-talk between autophagy and the TJ barrier has not yet been described. In this study, we present the novel finding that autophagy enhances TJ barrier function in Caco-2 intestinal epithelial cells. Nutrient starvation-induced autophagy significantly increased transepithelial electrical resistance and reduced the ratio of sodium/chloride paracellular permeability. Nutrient starvation reduced the paracellular permeability of small-sized urea but not larger molecules. The role of autophagy in the modulation of paracellular permeability was confirmed by pharmacological induction as well as pharmacological and genetic inhibition of autophagy. Consistent with the autophagy-induced reduction in paracellular permeability, a marked decrease in the level of the cation-selective, pore-forming TJ protein claudin-2 was observed after cell starvation. Starvation reduced the membrane presence of claudin-2 and increased its cytoplasmic, lysosomal localization. Therefore, our data show that autophagy selectively reduces epithelial TJ permeability of ions and small molecules by lysosomal degradation of the TJ protein claudin-2.
The Effects of Military Assignments and Duties on the Martial Status of Navy Officers

Abstract : This study seeks to determine if military duties and assignments affect the marriage and divorce decisions of United States Navy officers. Previous studies suggest that a stable marriage can have a positive influence on a military member's performance. However, no previous research has looked specifically at how duties and assignments may affect the marital status of Navy officers. This thesis presents an overview of duty types in the Navy and various factors that are believed to affect the marriage and divorce decisions of Navy officers. Based on the literature review, five hypotheses are generated and tested by estimating 32 logit models. The results show that military duties and assignments, gender, and commissioning sources significantly affect the likelihood and timing of marriage and divorce decisions of Navy officers. The results provide important information that can be used by policy makers to help reduce the adverse effects of duties and assignments on Navy marriages. The study also looks at the relationship between marriage on divorce and the member's decision to leave the Navy. It is recommended that further research be conducted regarding the effects of duties and assignments on divorce for enlisted personnel and members of other US armed forces.
Impairment of paravascular clearance pathways in the aging brain

In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF–ISF exchange and interstitial solute clearance is impaired in the aging brain.
Towards an occupational exposure limit for endotoxins

Endotoxins are part of the outer membrane of Gram-negative bacteria and are present ubiquitously in the environment. The lipopolysaccharide (LPS) part of the molecule is responsible for its toxic properties. Environmental monitoring is usually performed by sampling airborne dust and subsequent analysis of aqueous extracts by using a LAL assay. The kinetic version of this assay can measure concentrations as low as in the pg/m 3 range. A generally accepted protocol is not yet available. Endotoxin levels are related to the occurrence of Gram-negative bacteria. Animal faeces and bacteria contaminated plant materials contribute most to organic dust related endotoxin exposure. Endotoxin exposure is therefore most prevalent in agricultural and related industries. Acute health effects are dry cough and shortness of breath accompanied by a decrease in lung function, fever reaction and malaise, and sometimes dyspnea and headaches occurring a few hours after the start of the endotoxin exposure. Epidemiological and experimental studies suggest that chronic endotoxin exposure may lead to chronic bronchitis and reduced lung function. Depending of the relevant health effect, no effect levels range from 9 to 170 ng/m 3 . The Dutch Expert Committee on
Increased Spinal Cord Na+-K+-2Cl− Cotransporter-1 (NKCC1) Activity Contributes to Impairment of Synaptic Inhibition in Paclitaxel-induced Neuropathic Pain*

Background: Spinal synaptic plasticity may contribute to paclitaxel-induced painful neuropathy. Results: Paclitaxel treatment impairs GABA-mediated neuronal inhibition and increases total and plasma membrane NKCC1 protein levels in the spinal cord. Blocking NKCC1 reverses paclitaxel effects on synaptic inhibition and pain hypersensitivity. Conclusion: Paclitaxel diminishes synaptic inhibition in the spinal cord. Significance: This study demonstrates how disrupting microtubule dynamics causes synaptic plasticity and neuropathic pain. Microtubule-stabilizing agents, such as paclitaxel (Taxol), are effective chemotherapy drugs for treating many cancers, and painful neuropathy is a major dose-limiting adverse effect. Cation-chloride cotransporters, such as Na+-K+-2Cl− cotransporter-1 (NKCC1) and K+-Cl− cotransporter-2 (KCC2), critically influence spinal synaptic inhibition by regulating intracellular chloride concentrations. Here we show that paclitaxel treatment in rats significantly reduced GABA-induced membrane hyperpolarization and caused a depolarizing shift in GABA reversal potential of dorsal horn neurons. However, paclitaxel had no significant effect on AMPA or NMDA receptor-mediated glutamatergic input from primary afferents to dorsal horn neurons. Paclitaxel treatment significantly increased protein levels, but not mRNA levels, of NKCC1 in spinal cords. Inhibition of NKCC1 with bumetanide reversed the paclitaxel effect on GABA-mediated hyperpolarization and GABA reversal potentials. Also, intrathecal bumetanide significantly attenuated hyperalgesia and allodynia induced by paclitaxel. Co-immunoprecipitation revealed that NKCC1 interacted with β-tubulin and β-actin in spinal cords. Remarkably, paclitaxel increased NKCC1 protein levels at the plasma membrane and reduced NKCC1 levels in the cytosol of spinal cords. In contrast, treatment with an actin-stabilizing agent had no significant effect on NKCC1 protein levels in the plasma membrane or cytosolic fractions of spinal cords. In addition, inhibition of the motor protein dynein blocked paclitaxel-induced subcellular redistribution of NKCC1, whereas inhibition of kinesin-5 mimicked the paclitaxel effect. Our findings suggest that increased NKCC1 activity contributes to diminished spinal synaptic inhibition and neuropathic pain caused by paclitaxel. Paclitaxel disrupts intracellular NKCC1 trafficking by interfering with microtubule dynamics and associated motor proteins.
Le contrôle thérapeutique des médicaments antidépresseurs

Depression is a pathology frequently observed in general medicine (10%). Treatment of depression makes great use of drugs from different pharmacological classes. The optimal posology is difficult to establish, and clinicians prefer to avoid side effects by prescribing low regimen. This study is related to an evaluation of seric antidepressant concentrations in comparison with the daily doses in a large psychiatric population. Side effects of drugs are appreciated by enzymatic determinations.