Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Ganglionic Long-Term Potentiation Decreases Blood Pressure in Spontaneously Hypertensive Rats

Long-term potentiation of sympathetic ganglia (gLTP), a unique form of synaptic plasticity, is serotonin dependent and can be blocked with 5-HT3 receptor antagonists. Long-lasting enhancement of the basal tone of ganglionic transmission (as with gLTP) is expected to result in sustained increase in peripheral resistance that would lead to elevated blood pressure. We examined the possibility that in sympathetic ganglia, gLTP may be involved in the expression of stress-induced (neurogenic) form of hypertension. High blood pressure in spontaneously hypertensive rat (SHR), known to show exaggerated cardiovascular defense reactions to environmental stimuli, is partly due to a neurogenic factor. Chronic treatment of SHR and their normotensive counterpart, the Wistar Kyoto (WKY) rats with the 5-HT3 receptor antagonist tropisetron (ICS; 5 mg/kg/day), caused a marked decrease in the blood pressure of the SHR but not of WKY rats. Increasing the daily dose of ICS cumulatively (7 and 10 mg/kg) did not result in significant additional decrease in blood pressure of SHR, indicating that the drug blocks only the neurogenic component of hypertension in the SHR. electrophysiological procedures for indirectly testing for the presence of gLTP in ganglia excised from SHR suggest that gLTP has been previously expressed in these ganglia in vivo. This contrasts with the absence of gLTP in ganglia from normotensive rats. The results support contribution of gLTP to the expression of neurogenic hypertension.
INFLUENCE OF SUPPLY CHAIN MANAGEMENT PRACTICES ON COMPETITIVE ADVANTAGE IN CEMENT MANUFACTURING INDUSTRY: A CASE OF EAST AFRICA PORTLAND CEMENT COMPANY LIMITED

The supply chain management practices in manufacturing firms in Kenya are weak and there also exists little inter-industry integration in the country. They also encounter problems in materials management and lack of well integrated database system to support information flow as well as stiff competition in the current markets. The objective of the study was to look into the influence of supply chain management practices on competitive advantage in the cement manufacturing industry, with a focus on East African Portland Cement Company Limited. The study specifically sought to examine the effect of strategic supplier partnership and customer relationship on competitive advantage of cement manufacturing firms in Kenya. The study adopted descriptive research design. The target population was 676 staff from three departments, namely, supply chain department, sales & marketing and production department in EAPCC. The sample size for the study was determined using Yemane’s formula (2007). The study collected primary data using questionnaires. Statistical Package for Social Sciences (SPSS) version 21 was used in the data analysis. The study found that strategic supplier partnership influenced competitive advantage in cement manufacturing industry. Strategic supplier partnership enhanced joint inventory management between the organization and the supplier and helped promote shared benefits and ongoing collaboration in key strategic areas like technology, products and market, strategic partnership promotes collaboration in products design. Customer relationship influenced competitive advantage at EAPCC. Close relationships with customers enabled the organizations’ customers to distinguish its products to competitors. The study recommended that manufacturing companies should strive to create and abide more on the strategic supplier partnership to create their competitive advantage. Companies should create better relations with their customers to earn their loyalty through improving their services and responding timely to customer complains which in turn will create their competitive advantage over competitors. Key Words: Strategic Supplier Partnership, Customer Relationship, Supply Chain Management
Transcriptional Coactivator Protein p300

The p300/cAMP response element-binding protein-binding protein (CBP) family members include human p300 and cAMP response element-binding protein-binding protein, which are both important transcriptional coactivators and histone acetyltransferases. Although the role of these enzymes in transcriptional regulation has been extensively documented, the molecular mechanisms of p300 and CBP histone acetyltransferase catalysis are poorly understood. Herein, we describe the first detailed kinetic characterization of p300 using full-length purified recombinant enzyme. These studies have employed peptide substrates to systematically examine the substrate specificity requirements and the kinetic mechanism of this enzyme. The importance of nearby positively charged residues in lysine targeting was demonstrated. The strict structural requirement of the lysine side chain was shown. The catalytic mechanism of p300 was shown to follow a ping-pong kinetic pathway and viscosity experiments revealed that product release and/or a conformational change were likely rate-limiting in catalysis. Detailed analysis of the p300 selective inhibitor Lys-CoA showed that it exhibited slow, tight-binding kinetics.
Oxaliplatin‐induced neurotoxicity: Acute hyperexcitability and chronic neuropathy

Oxaliplatin, a platinum‐based chemotherapeutic agent, is effective in the treatment of solid tumors, particularly colorectal cancer. During and immediately following oxaliplatin infusion, patients may experience cold‐induced paresthesias, throat and jaw tightness, and occasionally focal weakness. We assessed nerve conduction studies and findings on needle electromyography of patients with metastatic colorectal cancer before and during treatment with oxaliplatin. Twenty‐two patients had follow‐up studies within 48 h following oxaliplatin infusions, and 14 patients had follow‐up studies after 3–9 treatment cycles. Repetitive compound muscle action potentials and neuromyotonic discharges were observed in the first 24–48 h following oxaliplatin infusion, but resolved by 3 weeks. After 8–9 treatment cycles, sensory nerve action potential amplitudes declined, without conduction velocity changes or neuromyotonic discharges. The acute neurological symptoms reflect a state of peripheral nerve hyperexcitability that likely represents a transient oxaliplatin‐induced channelopathy. Chronic treatment causes an axonal neuropathy similar to other platinum‐based chemotherapeutic agents. Muscle Nerve 29: 387–392, 2004
The caloric value of labile body tissue in obese subjects.

The caloric balance normally varies from moment to moment. Food is taken intermittently, absorbed, stored, and used as needed for the continuous requirements of metabolism. Variations of diet and of physical activity on successive days cause temporary inequalities of energy intake and output. Long-term balance requires some system to smooth these fluctuations. In the present work we have endeavored to define one aspect of the system by correlating small changes in body weight with known variations of caloric intake. The ratio of these two quantities -the caloric equivalent of labile body weightsets an upper limit to the energy value of primary storage tissue. The caloric equivalent would be easy to measure if all changes in weight were due to caloric imbalance. In reality, however, various other processes-menstrual changes or venous congestion, for instance-cause body fluid to vary without relation to the caloric status of the individual. Any single measurement of energy balance and weight change fails to define the caloric equivalent because it provides no means to distinguish a specific change of weight from an accidental fluctuation of water balance. Measurement of the total fluid balance cannot resolve the difficulty, however, because a considerable amount of water is held intracellularly with glycogen and protein. If these substances are used for temporary storage of energy their accumulation and discharge will cause an obligate variation of fluid balance, quantitatively related to each caloric change, and thus part of the caloric equivalent. Possibly the volume of extracellular fluid also varies with the caloric response. In any case, the distinction between caloric and noncaloric changes of hydration can be made only by repetition of the measurement, since a specific response to caloric variation is defined solely by the fact of its consistent occurrence. Standard methods for measurement of heat production-a calorimeter room (1) or an exact determination of water loss (2)-would be inconvenient for use in prolonged experiments such as are required by repeated changes of dietary intake. Fortunately, the average energy balance and the caloric equivalent can be measured more easily, and with greater accuracy, by an analysis of the weight response alone. Two known levels of dietary intake are equivalent in this case to the usual pair of data: one known level of intake and the measured rate of heat production. An additional advantage of the method is that it measures the caloric equivalent and the average daily requirement for maintenance under conditions that simulate normal variations of diet.
Endothelial glucocorticoid receptor is required for protection against sepsis

The glucocorticoid receptor (GR) is ubiquitously expressed on nearly all cell types, but tissue-specific deletion of this receptor can produce dramatic whole organism phenotypes. In this study we investigated the role of the endothelial GR in sepsis in vivo and in vitro. Mice with an endothelial-specific GR deletion and controls were treated with 12.5 mg/kg LPS and phenotyped. Mice lacking GR showed significantly increased mortality, more hemodynamic instability, higher nitric oxide levels, and higher levels of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) compared with controls. There were no differences in rates of apoptosis or macrophage recruitment between the two groups. Both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression were increased after LPS challenge in mice with endothelial GR deficiency, and aminoguanidine, a specific iNOS inhibitor in mice was able to rescue hemodynamic collapse in these animals. In vitro, human umbilical vein cells (HUVECs) subjected to GR knockdown by siRNA showed increased expression of eNOS at baseline that persisted after treatment with LPS. Both eNOS and iNOS mRNA was increased by qPCR. In HUVECs lacking GR, NF-κB levels and NF-κB–dependent genes tissue factor and IL-6 were increased compared with controls. Thus, endothelial GR is a critical regulator of NF-κB activation and nitric oxide synthesis in sepsis.
Drinking careers of older male alcoholics in treatment as compared to younger alcoholics and to older social drinkers.

OBJECTIVE In order to answer the question whether older alcoholics form a distinct group among problem drinkers and within their age cohort, drinking histories of male, older (over 50 years of age) alcoholics in treatment (n = 52) are compared to those of younger alcoholics (n = 55), and to those of older social drinkers (n = 46). Within the older alcoholics category, comparisons are made by age of onset. Changes in consumption volume and onset and remission of heavy drinking, morning drinking and solitary drinking are related to events in other spheres of life. METHOD In face-to-face interviews, respondents were asked to report drinking behavior in subsequent drinking phases, from the beginning of regular drinking to the present. Events that marked a transition to a new drinking phase, as well as the impact that these events had on the general well-being of the respondents, were assessed using a semistructured interview format. RESULTS Compared to younger alcoholics, older alcoholics were older when they started drinking regularly, and they report later age at onset of heavy drinking. Older alcoholics and social drinkers were similar with respect to the first years of their drinking career. Older alcoholics with onset of heavy drinking before the age of 35 were similar to younger alcoholics, while older alcoholics with later onset of heavy drinking resembled social drinkers with respect to their earlier drinking history. Alcoholics with later onset more often reported onset in connection with events such as marital disruption. CONCLUSION Among older alcoholics, a distinct group can be distinguished that may benefit from specific prevention and treatment measures.
New fully covered large‐bore wide‐flare removable metal stent for drainage of pancreatic fluid collections: Results of a multicenter study

Endoscopic transmural drainage (ETMD) of peripancreatic fluid collections (PFC) is an effective alternative to surgical drainage. Conventional drainage using plastic stents has its limitations. A wide‐bore short‐length wide flange fully covered self‐expandable metallic stent (FCSEMS) has recently been developed. The present study evaluates the efficacy of this new FCSEMS for ETMD of PFC.
Induction of delayed-type hypersensitivity to Leishmania major and the concomitant acceleration of disease development in progressive murine cutaneous leishmaniasis

BALB/c mice injected intradermally with 10(5) or higher doses of formaldehyde-fixed promastigotes (FFP) of Leishmania major developed strong delayed-type hypersensitivity (DTH) to leishmanial antigens injected into the hind footpad 3 to 10 days later. The DTH peaked 15 to 18 h after footpad injection and disappeared by 48 h. This specific DTH correlated with the homing of 51Cr-labeled syngeneic bone marrow cells and the infiltration of proliferating cells to the site of antigen administration. Spleen cells from FFP-sensitized mice also gave significant proliferative response to FFP in vitro. The DTH was adoptively transferable by Lyt-1+2-L3T4+ T cells and was H-2 restricted. DTH could be substantially enhanced by pretreatment with cyclophosphamide or pertussigen. Such DTH enhancement was accompanied by concomitant exacerbation of disease progression after L. major infection. Mice injected intravenously with FFP developed substantial immunity to cutaneous leishmaniasis but specifically suppressed DTH reactivity. Treatment of mice with pertussigen before intravenous immunization, however, abolished the protection and reversed the suppression of DTH. These results therefore demonstrate that the early-appearing type of DTH is not involved in host protection but that it actually facilitates disease progression in cutaneous leishmaniasis. Further evidence, which also shows the nonspecific nature of this disease exacerbation, is provided by local cell transfer experiments. Splenic T cells from mice sensitized to keyhole limpet hemocyanin or FFP induced significantly larger lesions compared with normal T cells when they were transferred into the footpad together with specific antigen and L. major promastigotes.
Management of the paediatric patient with acute head trauma

Head trauma leading to brain injury is an important cause of morbidity and mortality in childhood. Injury severity is related to the mechanism of trauma, which itself varies with age. The vast majority of head trauma in paediatric patients is mild, requires no specific therapy and leaves no sequelae. However, it is important to identify individuals at risk of significant injury, and thus in need of specific evaluation. The purpose of this statement is to describe issues related to head trauma in infants, children and youth, including clinical manifestations, initial management priorities, guidelines for imaging, and subsequent observation and treatment. It addresses the evaluation of patients with acute trauma to the head at the time of initial assessment; it does not describe the subsequent management of such patients in the paediatric intensive care unit.
The Effect of Levetiracetam on Closure of the Midline in Early Chicken Embryos.

AIM Genetic predisposition and some environmental factors play an important role in the development of neural tube defects. Levetiracetam is a new drug that has been approved in the treatment of partial seizures. We aimed in this study to determine the effect of levetiracetam on chick embryos. MATERIAL AND METHODS One hundred and sixty fertile non-pathogenic Super Nick eggs were incubated for 24 hours and were divided into four groups of 40 eggs each. Levetiracetam was administered via the sub-blastodermic route. The eggs were incubated for another 24 hours. All eggs were opened at the 48th hour, and the embryos were evaluated morphologically and histopathologically. RESULTS The effects of levetiracetam on the embryo were correlated with the dose of levetiracetam. In the light of the results, it was determined that the use of increasing doses of levetiracetam led to defects of midline closure in early chicken embryos. CONCLUSION Levetiracetam, a new antiepileptic drug that is effective especially on calcium ion concentration, leads to defects in midline closure in embryos in a dose-dependent manner. Further studies are needed to show the mechanism of embryonic damage and the mechanisms of its teratogenous effects associated with genetic and environmental factors.
A Novel YAP1 Inhibitor Targets CSC-Enriched Radiation-Resistant Cells and Exerts Strong Antitumor Activity in Esophageal Adenocarcinoma

Mounting evidence suggests that the Hippo coactivator Yes-associated protein 1 (YAP1) is a major mediator of cancer stem cell (CSC) properties, tumor progression, and therapy resistance as well as often a terminal node of many oncogenic pathways. Thus, targeting YAP1 may be a novel therapeutic strategy for many types of tumors with high YAP1 expression, including esophageal adenocarcinoma. However, effective YAP1 inhibitors are currently lacking. Here, we identify a small molecule (CA3) that not only has remarkable inhibitory activity on YAP1/Tead transcriptional activity but also demonstrates strong inhibitory effects on esophageal adenocarcinoma cell growth especially on YAP1 high–expressing esophageal adenocarcinoma cells both in vitro and in vivo. Remarkably, radiation-resistant cells acquire strong cancer stem cell (CSC) properties and aggressive phenotype, while CA3 can effectively suppress these phenotypes by inhibiting proliferation, inducing apoptosis, reducing tumor sphere formation, and reducing the fraction of ALDH1+ cells. Furthermore, CA3, combined with 5-FU, synergistically inhibits esophageal adenocarcinoma cell growth especially in YAP1 high esophageal adenocarcinoma cells. Taken together, these findings demonstrated that CA3 represents a new inhibitor of YAP1 and primarily targets YAP1 high and therapy-resistant esophageal adenocarcinoma cells endowed with CSC properties. Mol Cancer Ther; 17(2); 443–54. ©2017 AACR.
Retinoid‐enhanced gap junctional communication is achieved by increased levels of connexin 43 mRNA and protein

Natural and synthetic retinoids are potent inhibitors of experimental carcinogenesis in animals and cause reversion of premalignant lesions in humans. In the model C3H 10T1/2 cell system, retinoids enhance postconfluent growth control, reversibly inhibit carcinogen‐induced transformation, and enhance gap junctional intercellular communication. These effects are highly correlated. 10T1/2 cells were found to express low levels of connexin 43, a gap junctional protein first found in the heart. After treatment of confluent 10T1/2 cells with the synthetic retinoid tetrahydrotetramethylnapthalenylpropenylbenzoic acid (TTNPB), levels of connexin 43 mRNA and protein increased within 6 h of treatment, while elevation of junctional communication was detected within 12‐18 h. The maximally effective concentration of TTNPB (10−8 M) caused an approximate 10‐fold elevation of connexin 43 gene transcripts after 72 h. Indirect immunofluorescence microscopy using a polyclonal antibody to the synthetic C‐terminal region of connexin 43 demonstrated that TTNPB induced many fluorescent plaques in regions of cell‐cell contact. These results provide a molecular basis for the retinoid‐enhanced junctional communication in 10T1/2 cells. It is proposed that one action of retinoids is to modulate the intercellular transfer of signal molecules. These could mediate many of the physiological actions of retinoids on growth control and carcinogenesis.
Gastroretentive dosage forms: A review with special emphasis on floating drug delivery systems

In the present era, gastroretentive dosage forms (GRDF) receive great attention because they can improve the performance of controlled release systems. An optimum GRDF system can be defined as a system which retains in the stomach for a sufficient time interval against all the physiological barriers, releases active moiety in a controlled manner, and finally is easily metabolized in the body. Physiological barriers like gastric motility and gastric retention time (GRT) act as obstacles in developing an efficient GRDF. Gastroretention can be achieved by developing different systems like high density systems, floating drug delivery systems (FDDS), mucoadhesive systems, expandable systems, superporous systems, and magnetic systems. All these systems have their own merits and demerits. This review focused on the various aspects useful in development of GRDF including the current trends and advancements.
The Development of Validated Checklist for Foley Catheterization

Foley catheterization (FC) is known to result in complications. Validated checklists are central to teaching/assessing procedural skills and may result in improved health care quality. The results of the first step of the validation of male and female FC checklists are described. A comprehensive literature review of articles published on FC did not yield a checklist validated by the Delphi method. A modified Delphi technique involving a panel of 7 experts was used to develop FC checklists. The internal consistency coefficients using Cronbach’s α were . 91 and . 88, respectively, for males and females. Developing a 24-item male FC checklist and a 23-item female FC checklist for teaching/assessing FC is the first step in the validation process. For these checklists to become further validated, they should be implemented and studied in the simulation and the clinical environments.
Human fibrinogen bound to Streptococcus pyogenes M protein inhibits complement deposition via the classical pathway

Human fibrinogen (Fg) binds to surface proteins expressed by many pathogenic bacteria and has been implicated in different host–pathogen interactions, but the role of bound Fg remains unclear. Here, we analyse the role of Fg bound to Streptococcus pyogenes M protein, a major virulence factor that confers resistance to phagocytosis. Studies of the M5 system showed that a chromosomal mutant lacking the Fg‐binding region was completely unable to resist phagocytosis, indicating that bound Fg plays a key role in virulence. Deposition of complement on S. pyogenes occurred via the classical pathway even under non‐immune conditions, but was blocked by M5‐bound Fg, which reduced the amount of classical pathway C3 convertase on the bacterial surface. This property of M protein‐bound Fg may explain its role in phagocytosis resistance. Previous studies have shown that many M proteins do not bind Fg, but interfere with complement deposition and phagocytosis by recruiting human C4b‐binding protein (C4BP), an inhibitor of the classical pathway. Thus, all M proteins may share ability to recruit a human plasma protein, Fg or C4BP, which inhibits complement deposition via the classical pathway. Our data identify a novel function for surface‐bound Fg and allow us to propose a unifying mechanism by which M proteins interfere with innate immunity.