Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and Safety of Valganciclovir vs. Oral Ganciclovir for Prevention of Cytomegalovirus Disease in Solid Organ Transplant Recipients

We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high‐risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R‐). In this randomised, prospective, double‐blind, double‐dummy study, 364 CMV D+/R‐ patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post‐transplant. Endpoint committee‐defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type‐treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigator‐treated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p = 0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time‐to‐onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, once‐daily oral valganciclovir was as clinically effective and well‐tolerated as oral ganciclovir tid for CMV prevention in high‐risk SOT recipients.
Inter-arytenoid glottic bar following intubation

Abstract Inter-arytenoid glottic bar is a rare complication of prolonged endotracheal intubation. We present two such cases and their treatment. The aetiology of this complication is multifactorial and involves local factors—local tauma, movement of the endotracheal tube within the larynx, infection, and anatomical influences–together with systemic factors such as in our two cases. The relative importance of these factors is discussed. A comment is also made on the use of a pre-operative topogram and the importance of an ENT assessment in patients with airway problems following prolonged intubation.
Determinants of mortality and nondeath losses from an antiretroviral treatment service in South Africa: implications for program evaluation.

BACKGROUND The scale-up of antiretroviral treatment (ART) services in resource-limited settings requires a programmatic model to deliver care to large numbers of people. Understanding the determinants of key outcome measures--including death and nondeath losses--would assist in program evaluation and development. METHODS Between September 2002 and August 2005, all in-program (pretreatment and on-treatment) deaths and nondeath losses were prospectively ascertained among treatment-naive adults (n=1235) who were enrolled in a community-based ART program in South Africa. RESULTS At study censorship, 927 patients had initiated ART after a median of 34 days after enrollment in the program. One hundred twenty-one (9.8%) patients died. Mortality rates were 33.3 (95% CI, 25.5-43.0), 19.1 (95% CI, 14.4-25.2), and 2.9 (95% CI, 1.8-4.8) deaths/100 person-years in the pretreatment interval, during the first 4 months of ART (early deaths), and after 4 months of ART (late deaths), respectively. Pretreatment and early treatment deaths together accounted for 87% of deaths, and were independently associated with advanced immunodeficiency at enrollment. Late deaths were comparatively few and were only associated with the response to ART at 4 months. Nondeath program losses (loss to follow-up, 2.3%; transfer-out, 1.9%; relocation, 0.7%) were not associated with immune status and were evenly distributed during the study period. CONCLUSIONS Loss to follow-up and late mortality rates were low, reflecting good cohort retention and treatment response. However, the extremely high pretreatment and early mortality rates indicate that patients are enrolling in ART programs with far too advanced immunodeficiency. Causes of late access to the ART program, such as delays in health care access, health system delays, or inappropriate treatment criteria, need to be addressed.
Comparative effects of sediment versus aqueous polychlorinated biphenyl (PCB) exposure on benthic and planktonic invertebrates

Polychlorinated biphenyls (PCBs) are an environmental concern because of their adverse effects on humans and wildlife, and understanding the contribution of various matrices (i.e., sediment and water) to PCB exposure on aquatic communities is critical for successful remediation of impacted sites. The present study examined the toxicity of different routes of PCB exposure in aquatic invertebrates. In complementary laboratory and field experiments, the authors compared the effects of aqueous versus sedimentary exposure of PCBs on invertebrates. In laboratory bioassays, the planktonic Daphnia pulex and benthic Chironomus dilutus exhibited significant mortality when exposed to PCB‐contaminated (1100 µg/g) sediment (p = 0.03 and p < 0.01, respectively). In field experiments, adult Dreissena bugensis were placed in cages along a depth gradient at a reference site and a PCB‐impacted site in St. Clair Shores, Michigan, USA. Mussels experienced significantly greater mortality (p < 0.001) when placed in close proximity to impacted‐site sediments compared with reference sediments. After 7 d, 94% of D. bugensis survived at the reference site compared with only 57% surviving at the impacted site. In addition, D. bugensis at the impacted site experienced significantly less mortality at the water surface (p < 0.001) compared to those near the sediment. The present study demonstrates the importance of evaluating toxicity at the sediment–water interface. Environ Toxicol Chem 2014;33:641–647. © 2013 SETAC
hRRN3 is essential in the SL1‐mediated recruitment of RNA Polymerase I to rRNA gene promoters

A crucial step in transcription is the recruitment of RNA polymerase to promoters. In the transcription of human rRNA genes by RNA Polymerase I (Pol I), transcription factor SL1 has a role as the essential core promoter binding factor. Little is known about the mechanism by which Pol I is recruited. We provide evidence for an essential role for hRRN3, the human homologue of a yeast Pol I transcription factor, in this process. We find that whereas the bulk of human Pol I complexes (Iα) are transcriptionally inactive, hRRN3 defines a distinct subpopulation of Pol I complexes (Iβ) that supports specific initiation of transcription. Human RRN3 interacts directly with TAFI110 and TAFI63 of promoter‐selectivity factor SL1. Blocking this connection prevents recruitment of Pol I β to the rDNA promoter. Furthermore, hRRN3 can be found in transcriptionally autonomous Pol I holoenzyme complexes. We conclude that hRRN3 functions to recruit initiation‐competent Pol I to rRNA gene promoters. The essential role for hRRN3 in linking Pol I to SL1 suggests a mechanism for growth control of Pol I transcription.
Role of Intermediate Progenitor Cells in Cerebral Cortex Development

Intermediate progenitor cells (IPCs) are a type of neurogenic transient amplifying cells in the developing cerebral cortex. IPCs divide symmetrically at basal (abventricular) positions in the neuroepithelium to produce pairs of new neurons or, in amplifying divisions, pairs of new IPCs. In contrast, radial unit progenitors (neuroepithelial cells and radial glia) divide at the apical (ventricular) surface and produce only single neurons or single IPCs by asymmetric division, or self-amplify by symmetric division. Histologically, IPCs are most prominent during the middle and late stages of neurogenesis, when they accumulate in the subventricular zone, a progenitor compartment linked to the genesis of upper neocortical layers (II–IV). Nevertheless, IPCs are present throughout cortical neurogenesis and produce neurons for all layers. In mice, changes in the abundance of IPCs caused by mutations of Pax6, Ngn2, Id4 and other genes are associated with parallel changes in cortical thickness but not surface area. In gyrencephalic brains, IPCs may play broader roles in determining not only laminar thickness, but also cortical surface area and gyral patterns. We propose that regulation of IPC genesis and amplification across developmental stages and regional subdivisions modulates laminar neurogenesis and contributes to the cytoarchitectonic differentiation of cortical areas.
HLA DQ alleles and interleukin-10 polymorphism associated with Chlamydia trachomatis-related tubal factor infertility: a case-control study.

BACKGROUND The relationship between Chlamydia trachomatis tubal factor infertility (TFI) and the host's immunoregulatory genes was studied. METHODS Cell-mediated immune responses to C. trachomatis and chlamydial heat shock protein (CHSP60) were determined by lymphocyte proliferation assay. HLA-DQ alleles and interleukin-10 (IL-10) promoter polymorphism (-1082 A/G) were analysed in 52 TFI cases and in 61 controls by PCR. RESULTS HLA-DQB1 or DQA1 alleles did not significantly differ between the TFI group and the control group. However, DQA1*0102 and DQB1*0602 alleles together with IL-10 -1082AA genotype were found significantly more frequently in the TFI patients than in the controls (0.18 and 0.02 respectively; P = 0.005). Five (22%) of the 23 patients who had a positive lymphocyte proliferative response to CHSP60 were positive also for IL-10 -1082AA and for the HLA-DQA1*0102 and HLA-DQB1*0602 alleles. CONCLUSIONS Our results reveal an association of a cellular immune response to CHSP60, HLA class II alleles and IL-10 promoter genotypes in patients with chlamydial TFI.
TISSUE HYPOXIA ACTIVATES JNK IN THE LIVER DURING HEMORRHAGIC SHOCK

The earliest signaling pathways responsible for initiating the systemic response to hemorrhagic shock (HS) remain poorly characterized. We have investigated the involvement of the mitogen-activated protein (MAP) kinase C-JUN N-terminal kinase (JNK) and its activation in the liver as an early response to tissue hypoxia soon after the initiation of hemorrhage. In the present studies, hemorrhage of mice to 25 mmHg for 30 min resulted in a significant (2.1-fold) increase in JNK phosphorylation within the liver. Results were similar in rats hemorrhaged to 40 mmHg for 1 h. Hypoxia alone, replicated by warm isolated hepatic ischemia in vivo or hepatocytes cultured under 1% oxygen, also resulted in JNK phosphorylation. Finally, preservation of tissue perfusion and oxygenation by pretreatment with a blood-soluble drag-reducing polymer (DRP) in the rat HS model prevented phosphorylation of JNK in the liver. These results identify tissue hypoxia as a key factor in activating early signaling events in the liver following hemorrhage, as measured by JNK phosphorylation.
Cloning and sequencing of the cell division gene pbpB, which encodes penicillin-binding protein 2B in Bacillus subtilis

The pbpB gene, which encodes penicillin-binding protein (PBP) 2B of Bacillus subtilis, has been cloned, sequenced, mapped, and mutagenized. The sequence of PBP 2B places it among the class B high-molecular-weight PBPs. It appears to contain three functional domains: an N-terminal domain homologous to the corresponding domain of other class B PBPs, a penicillin-binding domain, and a lengthy carboxy extension. The PBP has a noncleaved signal sequence at its N terminus that presumably serves as its anchor in the cell membrane. Previous studies led to the hypothesis that PBP 2B is required for both vegetative cell division and sporulation septation. Its sequence, map site, and mutant phenotype support this hypothesis. PBP 2B is homologous to PBP 3, the cell division protein encoded by pbpB of Escherichia coli. Moreover, both pbpB genes are located in the same relative position within a cluster of cell division and cell wall genes on their respective chromosomes. However, immediately adjacent to the B. subtilis pbpB gene is spoVD, which appears to be a sporulation-specific homolog of pbpB. Inactivation of SpoVD blocked synthesis of the cortical peptidoglycan in the spore, whereas carboxy truncation of PBP 2B caused cells to grow as filaments. Thus, it appears that a gene duplication has occurred in B. subtilis and that one PBP has evolved to serve a common role in septation during both vegetative growth and sporulation, whereas the other PBP serves a specialized role in sporulation.
Summary of human studies to evaluate the hypocholesterolaemic properties of fermented milk products

For the past 20 years, the principal focus of public health strategies for reducing the risk of coronary heart disease (CHD) has been aimed at lowering serum cholesterol levels. However, recent findings have highlighted not only cholesterol but also triacylglycerol as a significant lipid risk factor for CHD. Dietary strategies which are able to reduce these circulating lipid levels and which are able to offer long-term efficacy comparable with effective drug treatments are currently being sought. One dietary strategy that may benefit the lipid profile involves supplementation of the diet with prebiotics, probiotics and synbiotics; this method improves the health of the host by supplementation with and/or fortification of certain health promoting bacteria present in the gastrointestinal tract, by dietary means. Probiotics (live organisms) in the form of fermented milk products have been shown to exert cholesterol lowering properties, whereas non-digestible fermentable carbohydrate prebiotics have been shown to reduce triacylglycerol levels in animal studies. However, in human studies using both prebiotics and probiotics, there have been inconsistent findings with respect to changes in lipid levels, although, on the whole, there have been favourable outcomes.
The European Union's Foreign Policy in Comparative Perspective : Beyond the “Actorness and Power” Debate

Introduction: The European Union's Foreign Policy 'Actorness and Power': Foundations of and Challenges for a Comparative Research Design Ingo Peters Part 1 Foreign Economic Policy 2 IMF Reform Negotiations in the G20: Comparing Actorness and Power in the Foreign Financial Policies of the EU, the US and ASEAN Steffen Murau and Kilian Spandler 3 The EU in Global Chemicals Governance Katja Biedenkopf 4 The External Reach of the EU Regulatory State: Norway, Russia and the Security of Natural Gas Supplies Nick Sitter and Svein S. Andersen Part 2 Common Foreign and Security Policy/ Peace- and State-building 5 The European Union and the Balkan Wars: Zivilmacht Europa and the "Problem from Hell" Adrian G. V. Hyde-Price 6 EU Performance As A Regional Security Actor: Comparing ENP South to NATO's MENA Policy Pernille Rieker 7 The EU and the US Reactions to the Arab Spring 2011: (New) Response to a Changing Middle East and North Africa Assem Dandashly Part 3 Crisis Management, Missions and Operations 8 State-Building and Police Reform in Afghanistan:EU and US Engagement in Comparative Perspective Dinoj Kumar Upadhyay and Maria Pawelec 9 The European Union's Foreign Policy in Comparative Perspective: The EU and the US in the Sahel Ronja Kempin, Ronja Scheler, and Stefan Steinicke 10 Building a Comprehensive Approach "Bottom Up": A Systematic Comparison of the EU's, the US' and NATO's Strategies for Providing Security to the Horn of Africa Bjorn Olav Knutsen and Eirik Donjar 11 The European Union, the United Nations and the United States Missions and Operations in the Democratic Republic of Congo in Comparative Perspective Ingo Peters and Madina Diallo Conclusions: Actorness and Power of the European Union in Comparative Perspective Ingo Peters
Inhibition of oligodendrocyte precursor cell differentiation by myelin-associated proteins.

OBJECT Promoting repair of central nervous system (CNS) white matter represents an important approach to easing the course of a number of tragic neurological diseases. For this purpose, strategies are currently being evaluated for transplanting cells capable of generating new oligodendrocytes into areas of demyelination and/or enhancing the potential of endogenous stem/precursor cells to give rise to new oligodendrocytes. Emerging evidence, however, indicates that increasing the presence of cells capable of forming new myelin sheaths is not sufficient to promote repair because of unknown inhibitors that accumulate in lesions as a consequence of myelin degeneration and impair the generation of new oligodendrocytes. The aim of the present study was to characterize the nature of the inhibitory molecules present in myelin. METHODS Differentiation of primary rat oligodendrocyte precursor cells (OPCs) in the presence of CNS and peripheral nervous system myelin was assessed by immunocytochemical methods. The authors further characterized the nature of the inhibitors by submitting myelin membrane preparations to biochemical precipitation and digestion. Finally, OPCs were grown on purified Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, the most prominent inhibitors of axon regeneration. RESULTS Myelin membrane preparations induced a differentiation block in OPCs that was associated with down-regulation of expression of the transcription factor Nkx2.2. The inhibitory activity in myelin was restricted to the CNS and was predominantly associated with white matter. Furthermore, the results demonstrate that myelin proteins that are distinct from the most prominent inhibitors of axon outgrowth are specific inhibitors of OPC differentiation. CONCLUSIONS The inhibitory effect of unknown myelin-associated proteins should be considered in future treatment strategies aimed at enhancing CNS repair.
Cloning and nucleotide sequencing of genes for small, acid-soluble spore proteins of Bacillus cereus, Bacillus stearothermophilus, and "Thermoactinomyces thalpophilus"

As found previously with other Bacillus species, spores of B. stearothermophilus and "Thermoactinomyces thalpophilus" contained significant levels of small, acid-soluble spore proteins (SASP) which were rapidly degraded during spore germination and which reacted with antibodies raised against B. megaterium SASP. Genes coding for a B. stearothermophilus and a "T. thalpophilus" SASP as well as for two B. cereus SASP were cloned, their nucleotide sequences were determined, and the amino acid sequences of the SASP coded for were compared. Strikingly, all of the amino acid residues previously found to be conserved in this group of SASP both within and between two other Bacillus species (B. megaterium and B. subtilis) were also conserved in the SASP coded for by the B. cereus genes as well as those coded for by the genes from the more distantly related organisms B. stearothermophilus and "T. thalpophilus. " This finding strongly suggests that there is significant selective pressure to conserve SASP primary sequence and thus that these proteins serve some function other than simply amino acid storage.
The phylogeny of the Schistosomatidae based on three genes with emphasis on the interrelationships of Schistosoma Weinland, 1858

Schistosomes are digenean flukes, parasitic of birds, mammals and crocodiles. The family Schistosomatidae contains species of considerable medical and veterinary importance, which cause the disease schistosomiasis. Previous studies, both morphological and molecular, which have provided a good deal of information on the phylogenetics of this group, have been limited in the number of species investigated or the type or extent of molecular data used. This paper presents the most comprehensive phylogeny to date, based on the sequences of 3 genes, complete ribosomal small subunit rRNA and large ribosomal subunit rRNA, and mitochondrial cytochrome oxidase 1, sequenced from 30 taxa including at least 1 representative from 10 of the 13 known genera of the Schistosomatidae and 17 of the 20 recognized Schistosoma species. The phylogeny is examined using morphological characters, intermediate and definitive host associations and biogeography. Theories as to the origins and spread of Schistosoma are also explored. The principal findings are that Ornithobilharzia and Austrobilharzia form a sister group to the Schistosoma; mammalian schistosomes appear paraphyletic and 2 Trichobilharzia species, T. ocellata and T. szidati, seem to be synonymous. The position of Orientobilharzia within the Schistosoma is confirmed, as is an Asian origin for the Schistosoma, followed by subsequent dispersal through India and Africa.
Confirmation of the Involvement of Protein Domain Movement during the Catalytic Cycle of the Cytochrome bc 1Complex by the Formation of an Intersubunit Disulfide Bond between Cytochrome b and the Iron-Sulfur Protein*

To study the essentiality of head domain movement of the Rieske iron-sulfur protein (ISP) duringbc 1 catalysis, Rhodobacter sphaeroides mutants expressing His-tagged cytochromebc 1 complexes with three pairs of cysteines engineered (one cysteine each) on the interface between cytochromeb and ISP, A185C(cytb)/K70C(ISP), I326C(cytb)/G165C(ISP), and T386C(cytb)/K164C(ISP), were generated and characterized. Formation of an intersubunit disulfide bond between cytochrome b and ISP is detected in membrane (intracytoplasmic membrane and air-aged chromatophore), and purified bc 1 complex was prepared from the A185C(cytb)/K70C(ISP) mutant cells. Formation of the intersubunit disulfide bond in this cysteine pair mutant complex is concurrent with the loss of its bc 1 activity. Reduction of this disulfide bond by β-mercaptoethanol restores activity, indicating that mobility of the head domain of ISP is functionally important in the cytochromebc 1 complex. The rate of intramolecular electron transfer, between 2Fe2S and hemec 1, in the A185C(cytb)/K70C(ISP) mutant complex is much lower than that in the wild type or in their respective single cysteine mutant complexes, indicating that formation of an intersubunit disulfide bond between cytochrome b and ISP arrests the head domain of ISP in the “fixed state” position, which is too far for electron transfer to heme c 1.
The Effect of Honey on Radiation-induced Oral Mucositis in Head and Neck Cancer Patients

Aim: The aim of this study is to evaluate the effect of honey on clinically scoring grades of oral mucositis. Materials and Methods: This interventional study was carried out in Radiation Oncology Department of Mayo Hospital, Lahore. In this study, 82 patients of both genders, of head and neck cancer, planned for radiotherapy, were divided into two groups by random sampling numbers. Patients in both groups were treated with a total dose of 60–78 Grays in 4–6 weeks. In treatment group, patients were instructed to take 20 mL of honey. In control group, they were advised to rinse with 0.9% of saline. Patients were evaluated every week to assess the grades of oral mucositis up to 6 weeks. The assessment tool was Radiation Therapy Oncology Group Grading System. The statistical analysis was done by Chi-square test. Results: In honey-treated group, the proportion of mucositis (Grades 3 and 4) was lower and statistically significant as compared to control group at the end of 6 weeks of radiation. Conclusion: This study showed that oral intake of honey during radiotherapy is valuable in the reduction of severity of oral mucositis.