Miracle-dz/UniFAR-FTUs huggingface dataset:
STUDIES ON EXPERIMENTAL HYPERTENSION

These experiments indicate that, in dogs at least, ischemia localized to the kidneys is a sufficient condition for the production of persistently elevated systolic blood pressure. When the constriction of both main renal arteries is made only moderately severe in the beginning, the elevation of systolic blood pressure is unaccompanied by signs of materially decreased renal function. In this respect the hypertension in these animals resembles the hypertension which is associated with so called benign nephrosclerosis in man. Subsequent increase of the constriction of the main renal arteries does not materially damage renal function, probably because of adequate development of accessory circulation. More delicate methods for detecting a change may yet prove that some damage does occur. Almost complete constriction of both main renal arteries, from the beginning, results in great elevation of systolic blood pressure which is accompanied by severe disturbance of renal function and uremia. This resembles the type of hypertension which is associated with so called malignant nephrosclerosis, in the sense of Fahr (17). In several of the animals with persistent elevation of systolic blood pressure, anatomical changes were observed in the glomeruli, vessels and parenchyma of the kidneys which are most probably directly referable to the ischemia. It is hoped that these investigations will afford a means of studying the pathogenesis of hypertension that is associated with renal vascular disease.
Update on the management of subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease. Outcome after SAH is mainly determined by the initial severity of the hemorrhage. Neuroimaging, in particular computed tomography, and aneurysm repair techniques, such as coiling and clipping, as well as neurocritical care management, have improved during the last few years. The management of a patient with SAH should have an interdisciplinary approach with case discussions between the neurointensivist, interventionalist and the neurosurgeon. The patient should be treated in a specialized neurointensive care unit of a center with sufficient SAH case volume. Poor-grade patients can be observed for complications and delayed cerebral ischemia through continuous monitoring techniques in addition to transcranial Doppler ultrasonography such as continuous electroencephalography, brain tissue oxygenation, cerebral metabolism, cerebral blood flow and serial vascular imaging. Neurocritical care should focus on neuromonitoring for delayed cereb.
CHO-gmt5, a novel CHO glycosylation mutant for producing afucosylated and asialylated recombinant antibodies

Engineered zinc-finger nucleases (ZFNs) are powerful tools for creating double-stranded-breaks (DSBs) in genomic DNA in a site-specific manner. These DSBs generated by ZFNs can be repaired by homology-directed repair or nonhomologous end joining, in which the latter can be exploited to generate insertion or deletion mutants. Based on published literature, we designed a pair of zinc-finger nucleases and inactivated the GDP-fucose transporter gene (Slc35c1) in a previously reported CHO mutant that has a dysfunctional CMP-sialic acid transporter gene (Slc35a1). The resulting mutant cell line, CHO-gmt5, lacks functional GDP-fucose transporter and CMP-sialic acid transporter. As a result, these cells can only produce asialylated and afucosylated glycoproteins. It is now widely recognized that removal of the core fucose from the N-glycans attached to Asn297 of human IgG1 significantly enhances its binding to its receptor, FcγRIIIa, and thereby dramatically improves antibody-dependent cellular cytotoxicity (ADCC). Recent reports showed that removal of sialic acid from IgG1 also enhances ADCC. Therefore, CHO-gmt5 may represent a more advantageous cell line for the production of recombinant antibodies with enhanced ADCC. These cells show comparable growth rate to wild type CHO-K1 cells and uncompromised transfection efficiency, which make them desirable for use as a production line.
Guidelines on Prostate Cancer

The introduction of an effective blood test, prostate specific antigen (PSA), has made it possible to diagnose more and more men in an earlier stage where they can be offered potentially curative treatments. The other side of the coin is that if effective diagnostic procedures are used unselectively in elderly men with a short life expectancy, a problem with over diagnosis and over treatment might occur. Thus the same stage of prostate cancer may need different treatment strategies, pending on the patient’s life expectancy. This, and many other issues regarding the disease, is the subject of the EAU guidelines on prostate cancer. G UI DE LI N ES O N P RO ST AT E CA N CE R 10
Conservation of Resources and Disaster in Cultural Context: The Caravans and Passageways for Resources

In this article, I build on Lawrence Palinkas’s empirical and theoretical approach and bring in more fully the focus of conservation of resources (COR) theory that Palinkas discusses. Palinkas analyzes technological disaster from psychological, sociological, and broader cultural perspectives. By more fully weaving in the principles and corollaries of COR theory, I attempt to more fully elaborate how the theoretical approach that Palinkas raises offers precise predictions, directions, and potentials for intervention and policy. I emphasize that personal, social, and material resources tend to develop and exist in aggregate, called resource caravans. Second, I introduce the concept that resource caravans are encouraged, discouraged, or outright prevented by environmental conditions that I call resource caravan passageways. This approach not only helps guide an understanding of the multiple tiers of devastation that likely will occur, it also guides insights regarding resiliency and rebuilding lives and communities, and reweaving the elements of culture that become torn when disasters have such major personal, social, and economic impact.
Regulatory T-cells in B-cell chronic lymphocytic leukemia: their role in disease progression and autoimmune cytopenias

Abstract Regulatory T-cells (Tregs) have been shown to be important for the balance of autoimmunity and oncogenesis. Tregs have a protective role in autoimmune diseases and conversely promote oncogenesis. Chronic lymphocytic leukemia (CLL) is unique in being at the cross-roads of oncogenesis and autoimmunity. We studied Tregs, defined as CD4+CD25highCD127lowFOXP3+, in 32 treatment-naive patients with CLL. Our study shows that patients with CLL had a higher absolute Treg count than the control group (p < 0.001). A progressive increase of Tregs was noted in advanced stages of the disease (p < 0.001). The increase in absolute Treg count is more significant than the increase in percentage Tregs. The absolute Treg count appears to be more important in disease pathogenesis. The absolute Treg count was significantly higher in those patients having autoimmune cytopenias. There was an inverse correlation between lymphocyte doubling time and absolute Treg count (p = 0.03). The absolute Treg count may be used as a prognostic marker in CLL.
High negativity of IgG antibodies against human papillomavirus type 6, 11, 16 and 18 virus-like particles in healthy women of childbearing age -

Objective: Few studies on human papillomavirus (HPV) seroprevalence have focused on low-resource areas where highest HPV DNA prevalence in the world occurs. This study aimed to assess the level of susceptibility to the most common low- and high-risk HPVs of sexually active women of childbearing age attending Wesley Guild Hospital, Ilesa, Osun State, Nigeria. Methods: A total of 91 such women (range 16-40, mean age 29.35 years) were consecutively recruited, after they had given consents to participate in the study. With interviewer-administered questionnaire, we collected pertinent demographic/behavioral data, and about 5 ml blood samples (aseptically) from each woman. Serum of each sample was assayed for HPV-6, -11, -16 and -18 virus-like particles using a HPV IgG ELISA kit. The results obtained were statistically analyzed using binary logistic regression. Results: We observed a high overall anti-HPV seronegativity of 93.4% among the women. Group-specific seronegativity was also high ranging from 86-100%. Though the mean age of the 3 age-groups (16-18, 19-30 and 31-40 years) significantly differed, none of their variables showed statistical association with the seronegativity. Conclusions: With our observations of low evidence (6.6% seropositivity) of natural exposure of the women to the studied HPVs and their low level of enlightenment regarding HPV infection and its attendant consequences, we recommend a statewide enlightenment campaign and adequate vaccination with quadrivalent HPV vaccine of sexually active females.
Mechanisms of action of fingolimod in multiple sclerosis

Fingolimod is a sphingosine 1‐phosphate receptor (S1PR) modulator approved as a therapy for multiple sclerosis. The present review will describe how interactions of fingolimod with S1PR, can induce the dual effects of inhibiting signaling and functional responses induced by S1P, the natural ligand for the S1PR, while continuing itself to induce active signaling and functional responses. These dual effects of fingolimod will be considered in terms of their mechanisms of actions on the systemic immune system, the blood–brain barrier, and within the central nervous system.
Rac1 mediates laminar shear stress-induced vascular endothelial cell migration

The migration of endothelial cells (ECs) plays an important role in vascular remodeling and regeneration. ECs are constantly subjected to shear stress resulting from blood flow and are able to convert mechanical stimuli into intracellular signals that affect cellular behaviors and functions. The aim of this study is to elucidate the effects of Rac1, which is the member of small G protein family, on EC migration under different laminar shear stress (5.56, 10.02, and 15.27 dyn/cm2). The cell migration distance under laminar shear stress increased significantly than that under the static culture condition. Especially, under relative high shear stress (15.27 dyn/cm2) there was a higher difference at 8 h (P < 0.01) and 2 h (P < 0.05) compared with static controls. RT-PCR results further showed increasing mRNA expression of Rac1 in ECs exposed to laminar shear stress than that exposed to static culture. Using plasmids encoding the wild-type (WT), an activated mutant (Q61L), and a dominant-negative mutant (T17N), plasmids encoding Rac1 were transfected into EA.hy 926 cells. The average net migration distance of Rac1Q61L group increased significantly, while Rac1T17N group decreased significantly in comparison with the static controls. These results indicated that Rac1 mediated shear stress-induced EC migration. Our findings conduce to elucidate the molecular mechanisms of EC migration induced by shear stress, which is expected to understand the pathophysiological basis of wound healing in health and diseases.
Relationship between blood pressure and arterial stiffness in patients undergoing antihypertensive treatment: A pilot study

Mean arterial blood pressure is one of the principal modifiable factors which contribute to arterial stiffness. The influence of anti hypertensive drugs on arterial stiffness measured photoplethysmographically has not yet been studied. This pilot study was aimed at exploring the relationship between blood pressure (BP) and parameters of arterial stiffness on initiating antihypertensive treatment. Fourteen newly diagnosed hypertensive male or female patients aged 30 to 40 years participated in the study. The age, height, weight and body mass index was calculated for all patients. BP and arterial stiffness were measured once before treatment and weakly after initiation of treatment for 3 weeks. On comparing the pretreatment and post treatment weakly BP values, a highly significant decline in the systolic BP (p< 0.006) and mean BP (0.005) was observed, whereas diastolic BP showed a significant (0.016) decline. Post hoc analysis revealed that systolic BP (SBP) and diastolic BP (DBP) showed a significant decline (p = 0.011 and 0.027, respectively) at the second visit, which was around two weeks post treatment, while the mean BP showed a highly significant decrease (p = 0.009) at this time. However, pulse pressure and heart rate did not change significantly with treatment. Also, the parameters of arterial stiffness did not change significantly with treatment for the same duration. Thus, we concluded that reduction in BP in hypertensive patients as measured clinically by brachial cuff sphygmanometry seems to be dependent on the encounter interval. The decrease in blood pressure occured within three weeks, whereas changes in arterial stiffness do not occur even till three weeks of initiating the treatment. Key words: Antihypertensive treatment, photoplethysmographic arterial stiffness, encounter interval.
Toxicity profile of thal-dex regime in patients with multiple myeloma

Background: To study the spectrum, incidence and severity of toxicity among Multiple Myeloma patients receiving Thal-Dex in South Indian population. Methods: Between November 2005 and November 2005, 25 adult patients with previously- untreated Multiple Myeloma were assigned to receive Thal-Dex at Regional Cancer Centre, Trivandrum. During chemotherapy, patients were followed-up to detect the development of any toxicity symptoms. The toxicities recorded, were graded according to the criteria of the World Health Organization toxicity-guidelines. Results: In the 25 patients who received Thal-Dex, peripheral neuropathy, infection and constipation were significantly seen, while gastrointestinal toxicities were seen to a lesser extent, and haematological toxicities were low. Conclusions: The Thal-Dex regimen was tolerated well by majority of the patients and showed favourable toxicity profile, reiterating its acceptability as a front line antimyeloma regimen
Localized ridge augmentation using guided tissue regeneration in humans. A report of nine cases.

Nine localized buccal ridge deformities were treated combining the use of barrier membranes and resorbable space-making material. After elevating flaps, the bone defects were completely filled with calcium carbonate and a fibrin-fibronectin sealing system (FFSS). Membranes (Gore-Tex aug-mentation material) were then shaped and positioned to cover the calcium carbonate overlapping the surrounding bone. The flaps were sutured, taking care to avoid any compression on the treated area. The membranes were removed 4 to 5 months postoperatively: in all cases the membranes were tightly adapted to the regenerated tissues and force was required to separate them from the underlying tissues. The defects were filled with hard, bone-like tissue. The histology from one case, taken 1 year post-operatively, confirmed the regeneration of bone and revealed the presence of a few residual particles of calcium carbonate in the sample. The clinical appearance of the treated areas was satisfactory for colour. texture and form. The horizontal deficiencies were almost completely resolved in all cases, while the vertical component showed incomplete filling in some cases.
Women’s perceptions of a midwife’s role: An initial investigation

Abstract The role of the midwife has evolved over the years, influenced by a number of social, political and educational factors (Department of Health and Social Security (DHSS), 1970; Her Majesty’s Stationery Office (HMSO), 1984; Tew, 1986; Donnison, 1988, Department of Health (DH), 1993; Kitzinger, 2005; DH, 2007; National Institute for Health and Clinical Excellence (NICE), 2008). However, little is known about how the contemporary role of the midwife is perceived (Lavender and Chappie, 2002). Some changes were not based on any evidence or health economics (DHSS, 1970; HMSO, 1984). Health costs have predominantly been based on the cost of service provision, rather than costs of unnecessary intervention being considered. The Birthplace study did take into account health economics including intervention costs (Shroeder et al, 2012); therefore, if service changes are made to reflect the benefit of health economics with the new maternity pathway payments (DH, 2012), this may impact on how the role of the m.
Descending Systems Direct Development of Key Spinal Motor Circuits

The formation of mature spinal motor circuits is dependent on both activity-dependent and independent mechanisms during postnatal development. During this time, reorganization and refinement of spinal sensorimotor circuits occurs as supraspinal projections are integrated. However, specific features of postnatal spinal circuit development remain poorly understood. This study provides the first detailed characterization of rat spinal sensorimotor circuit development in the presence and absence of descending systems. We show that the development of proprioceptive afferent input to motoneurons (MNs) and Renshaw cells (RCs) is disrupted by thoracic spinal cord transection at postnatal day 5 (P5TX). P5TX also led to malformation of GABApre neuron axo–axonic contacts on Ia afferents and of the recurrent inhibitory circuit between MNs and RCs. Using a novel in situ perfused preparation for studying motor control, we show that malformation of these spinal circuits leads to hyperexcitability of the monosynaptic reflex. Our results demonstrate that removing descending input severely disrupts the development of spinal circuits and identifies key mechanisms contributing to motor dysfunction in conditions such as cerebral palsy and spinal cord injury. SIGNIFICANCE STATEMENT Acquisition of mature behavior during postnatal development correlates with the arrival and maturation of supraspinal projections to the spinal cord. However, we know little about the role that descending systems play in the maturation of spinal circuits. Here, we characterize postnatal development of key spinal microcircuits in the presence and absence of descending systems. We show that formation of these circuits is abnormal after early (postnatal day 5) removal of descending systems, inducing hyperexcitability of the monosynaptic reflex. The study is a detailed characterization of spinal circuit development elucidating how these mechanisms contribute to motor dysfunction in conditions such as cerebral palsy and spinal cord injury. Understanding these circuits is crucial to developing new therapeutics and improving existing ones in such conditions.
Soccer & science—in an interdisciplinary perspective

Edited by Jens Bangsbo. Blackwell Publishing:Carlton, Victoria, Australia; 2000, pp 151. ISBN 87-16-12348-4 With a timely release prior to the 2006 World Cup in Germany, much was anticipated. I gather the idea was conceived at the second European Congress of Sport and Exercise Science held in Copenhagen in August 1997. This is part of a series of books, which includes other activities such as running and sailing. The front cover is certainly interesting, with an abstract painting—largely in the Swedish, Norweigan and Argentinian colours I might add! This book approaches soccer …
Characterization of the conversion between CD133+ and CD133- cells in colon cancer SW620 cell line

The state of cancer stem cells (CSC) under reversible fluctuations, which has been revealed in breast cancer cells most recently, suggests that subpopulations with distinct phenotypes and functions within cancer cells can undergo inter-conversion. To investigate the possibility in colon cancer cells, we employed CD133 as the CSC marker, and characterized CD133 expression pattern and the biological features of the CD133+ and CD133- subsets. Flow cytometry revealed that CD133 was bimodally expressed in SW620 cells among eight colon cancer cell lines. The CD133+ clonal SW620 cells displayed a differential gene expression profile, higher cellular reactive oxygen species (ROS), enhanced tumorigenesis and resistance to 5-fluorouracil. The conversion in term of the CD133 phenotype of the sorted cells was observed in vitro and in vivo. The fraction of the CD133+ cells decreased from 99% to 80% in the sorted CD133+ population while rising from 5 to 10% in the sorted CD133- population during the first 20-day cultivation and then stayed almost unchanged. A fraction (about 20%) of the CD133+ clonal cells lost their CD133 marker while about 10% of the CD133- clonal cells acquired the CD133 marker. 5-Azacytidine enhanced the fraction of the CD133+ cells in both of the CD133+ and CD133- clonal cells. Our data demonstrate that CD133 expression is dynamic and reversible, and reveal the inter-conversion between the CD133+ and the CD133- SW620 cells, suggesting that the CD133 phenotype of SW620 cell population is retained by the conversion between the two cell subsets.
Opening a New Time Window for Treatment of Stroke by Targeting HDAC2

Narrow therapeutic window limits treatments with thrombolysis and neuroprotection for most stroke patients. Widening therapeutic window remains a critical challenge. Understanding the key mechanisms underlying the pathophysiological events in the peri-infarct area where secondary injury coexists with neuroplasticity over days to weeks may offer an opportunity for expanding the therapeutic window. Here we show that ischemia-induced histone deacetylase 2 (HDAC2) upregulation from 5 to 7 d after stroke plays a crucial role. In this window phase, suppressing HDAC2 in the peri-infarct cortex of rodents by HDAC inhibitors, knockdown or knock-out of Hdac2 promoted recovery of motor function from stroke via epigenetically enhancing cells survival and neuroplasticity of surviving neurons as well as reducing neuroinflammation, whereas overexpressing HDAC2 worsened stroke-induced functional impairment of both WT and Hdac2 conditional knock-out mice. More importantly, inhibiting other isoforms of HDACs had no effect. Thus, the intervention by precisely targeting HDAC2 in this window phase is a novel strategy for the functional recovery of stroke survivors. SIGNIFICANCE STATEMENT Narrow time window phase impedes current therapies for stroke patients. Understanding the key mechanisms underlying secondary injury may open a new window for pharmacological interventions to promote recovery from stroke. Our study indicates that ischemia-induced histone deacetylase 2 upregulation from 5 to 7 d after stroke mediates the secondary functional loss by reducing survival and neuroplasticity of peri-infarct neurons as well as augmenting neuroinflammation. Thus, precisely targeting histone deacetylase 2 in the window phase provides a novel therapeutic strategy for stroke recovery.