Miracle-dz/UniFAR-FTUs huggingface dataset:
Vaccine-relevant human papillomavirus (HPV) infections and future acquisition of high-risk HPV types in men.

BACKGROUND Little is known about type-specific associations between prevalent human papillomavirus (HPV) infections and risk of acquiring other HPV types in men. Data on natural clustering of HPV types are needed as a prevaccine distribution to which postvaccine data can be compared. METHODS Using data from a randomized controlled trial of male circumcision in Kisumu, Kenya, adjusted mean survival ratios were estimated for acquisition of any-HPV, high-risk (HR) HPV, and individual HR-HPV types among men uninfected as compared to those infected with vaccine-relevant HPV types 16, 18, 31, 45, 6, or 11 at baseline. RESULTS Among 1097 human immunodeficiency virus-negative, uncircumcised men, 2303 incident HPV infections were detected over 2534 person-years of follow-up. Although acquisition of individual HR-HPV types varied by baseline HPV type, there was no clear evidence of shorter times to acquisition among men without vaccine-relevant HPV-16, -18, -31, -45, -6, or -11 infections at baseline, as compared to men who did have these infections at baseline. CONCLUSIONS These prospective data on combinations of HPV infections over time do not suggest the potential for postvaccination HPV type replacement. Future surveillance studies are needed to definitely determine whether elimination of HPV types by vaccination will alter the HPV type distribution in the population.
Enzyme-histochemical analysis of retinal development in the mouse

textabstractDevelopment of neuronal specificity remains one of the major enigmas in contemporary neurobiology. The embryonic neuroepithelium1 derived from the surface ectoderm due to the inductive influence of the chordamesoderm, acquires a high]_ycomplex differentiation when neuronal and glial cells appear and establish specific structural relationships. Arising as a protrusion of the diencephalon during ontogeny 1 the retina presents the same anatomical and physiological problems as do other parts of the central nervous system. In the retina a spatial separation of both the perikarya and the cell processes into distinct nuclear and synaptic layers is effected during histogenesis. Tills makes the retina a very suitable material for studying vertebrate neurogenesis and therefore the developing retina has been a preferred target of analysis through various approaches.
High‐level secretion of a recombinant protein to the culture medium with a Bacillus subtilis twin‐arginine translocation system in Escherichia coli

The twin‐arginine translocation (Tat) system transports folded proteins across the plasma membrane in bacteria, and heterologous proteins can be exported by this pathway if a Tat‐type signal peptide is present at the N‐terminus. The system thus has potential for biopharmaceutical production in Escherichia coli, where export to the periplasm is often a favoured approach. Previous studies have shown that E. coli cells can export high levels of protein by the Tat pathway, and the protein product accummulates almost exclusively in the periplasm. In this study, we analysed E. coli cells that express the Bacillus subtilis TatAdCd system in place of the native TatABC system. We show that a heterologous model protein, comprising the TorA signal peptide linked to green fluorescent protein (TorA–GFP), is efficiently exported by the TatAdCd system. However, whereas the GFP is exported initially to the periplasm during batch fermentation, the mature protein is increasingly found in the extracellular culture medium. By the end of a 16‐h fermentation, ~ 90% of exported GFP is present in the medium as active mature protein. The total protein profiles of the medium and periplasm are essentially identical, confirming that the outer membrane becomes leaky during the fermentation process. The cells are otherwise intact, and there is no large‐scale release of cytoplasmic contents. Export levels are relatively high, with ~ 0.35 g GFP·L−1 culture present in the medium. This system thus offers a means of producing recombinant protein in E. coli and harvesting directly from the medium, with potential advantages in terms of ease of purification and downstream processing.
Level and determinants of infant and child mortality in Malakal Town - southern Sudan.

This study aims to estimate the levels of infant and under five mortality rates in Malakal town and to determine the socioeconomic demographic and environmental factors contributing to infants and child mortality. The primary data for the study were collected using questionnaire and interviews in Malakal town Sudan while secondary data were collected from relevant literature. Three hundred eighty four women in the reproductive age (15-49) years were randomly chosen for the sample selected. The data were analyzed statistically using the Statistical Package for Social Sciences (SPSS). Frequency distributions and statistical test based on Chi-square for independence was conducted. The results revealed that infant mortality rate was 86 per 1000 live births while under five mortality was 108 deaths per 1000 live births. Also the study found that child interval child immunization family size family income and mothers education have significant influence on infant and under-five mortality. This shows the high need for infant and child immunization in Malakal town in addition to health education campaigns for parents and community in general.
Nosocomial transmission of extensively drug-resistant tuberculosis in a rural hospital in South Africa.

BACKGROUND Extensively drug-resistant tuberculosis (XDR-tuberculosis) is a global public health threat, but few data exist elucidating factors driving this epidemic. The initial XDR-tuberculosis report from South Africa suggested transmission is an important factor, but detailed epidemiologic and molecular analyses were not available for further characterization. METHODS We performed a retrospective, observational study among XDR-tuberculosis patients to identify hospital-associated epidemiologic links. We used spoligotyping, IS6110-based restriction fragment-length polymorphism analysis, and sequencing of resistance-determining regions to identify clusters. Social network analysis was used to construct transmission networks among genotypically clustered patients. RESULTS Among 148 XDR-tuberculosis patients, 98% were infected with human immunodeficiency virus (HIV), and 59% had smear-positive tuberculosis. Nearly all (93%) were hospitalized while infectious with XDR-tuberculosis (median duration, 15 days; interquartile range: 10-25 days). Genotyping identified a predominant cluster comprising 96% of isolates. Epidemiologic links were identified for 82% of patients; social network analysis demonstrated multiple generations of transmission across a highly interconnected network. CONCLUSIONS The XDR-tuberculosis epidemic in Tugela Ferry, South Africa, has been highly clonal. However, the epidemic is not the result of a point-source outbreak; rather, a high degree of interconnectedness allowed multiple generations of nosocomial transmission. Similar to the outbreaks of multidrug-resistant tuberculosis in the 1990s, poor infection control, delayed diagnosis, and a high HIV prevalence facilitated transmission. Important lessons from those outbreaks must be applied to stem further expansion of this epidemic.
``Composite particles'' and the eigenstates of Calogero-Sutherland and Ruijsenaars-Schneider

We establish a one-to-one correspondence between the “composite particles” with N particles and the Young tableaux with at most N rows. We apply this correspondence to the models of Calogero–Sutherland and Ruijsenaars–Schneider and we obtain a momentum space representation of the “composite particles” in terms of creation operators attached to the Young tableaux. Using the technique of bosonization, we obtain a position space representation of the “composite particles” in terms of products of vertex operators. In the special case where the “composite particles” are bosons and if we add one extra quasiparticle or quasihole, we construct the ground state wave functions corresponding to the Jain series ν=p/(2np±1) of the fractional quantum Hall effect.
El síndrome metabólico de la mujer posmenopáusica. Implicaciones clínicas

Cardiovascular diseases (CVD) remain the major cause of death in postmenopausal women. Before menopause, women are relatively protected from ischemic heart disease and thromboembolism by their circulating estrogens, but this protection is lost after menopause. Following menopause, adverse lipid changes occur and the levels of several coagulation factor increase. One of the major predisposing factors for CVD is the metabolic syndrome, including myriad risk biomarkers: abdominal girth, blood pressure, fasting glucose, triglycerides, lipids. In many ways, the metabolic syndrome is a precursor to the development of abnormalities of insulin action and diabetes. In parallel, there are effects upon blood coagulation and fibrinolysis. Common preventive therapies require rigorous evaluation. Hormone replacement therapy (HRT) has not produced the expected reduction in CVD and the ideal HRT is probably unobtainable. For long-term HRT users, the risk of thromboembolism needs to be weighed against probable benefits. With respect to the effects of HRT, oral estrogen is associated with elevation in C-reactive protein and varied effects on IL-6, but transdermal estradiol has no significant effect on these parameters. Despite the varied effects of HRT on inflammatory biomarkers, there is no definitive evidence that change in these markers results in modification of cardiovascular risk.
LEUKEMIA WITHOUT LEUKOCYTOSIS (ALEUKEMIC MYELOSIS) AND WITHOUT SPLENOMEGALY

It is well known that leukemia may occur without leukocytosis. In such cases the clinical picture of weakness and pallor and the varying degrees of lymphadenopathy, splenomegaly and hepatomegaly, with the blood picture of anemia and thrombopenia and the presence of myeloblasts in the stained blood film, make the diagnosis possible. The anatomic findings in the cases hitherto reported 1 show a similarity to the anatomic picture in true leukemia. There is, however, relatively little to be found in the medical literature on the occurrence of leukemia without splenomegaly. In a recent review 2 on leukemia it was mentioned that there are instances in which no splenic enlargement is noted. Hirschfeld 3 reported four cases of leukemia without splenomegaly, Ordway and Gorham 4 reported one case and Kracke and Garver 5 also described one case. Recently Parkes Weber 6 reported a case of aleukemic myelosis without splenic enlargement in which the condition
The calcium transporter Pmc1 provides Ca2+ tolerance and influences the progression of murine cryptococcal infection

The Ca2+‐calcineurin signaling pathway in the human fungal pathogen Cryptococcus neoformans is essential for adaptation to the host environment during infection. Calcium transporters regulate cytosolic calcium concentrations, providing Ca2+ loading into storage organelles. The three calcium transporters that have been characterized in C. neoformans, Cch1, Eca1 and Vcx1, are required for fungal virulence, supporting a role for calcium‐mediated signaling in cryptococcal pathogenesis. In the present study, we report the functional characterization of the putative vacuolar calcium ATPase Pmc1 in C. neoformans. Our results demonstrate that Pmc1 provides tolerance to high Ca2+ concentrations. The double knockout of C. neoformans PMC1 and VCX1 genes impaired the intracellular calcium transport, resulting in a significant increase in cytosolic calcium levels. Furthermore, Pmc1 was essential for both the progression of pulmonary infection and brain colonization in mice, emphasizing the crucial role of calcium signaling and transport for cryptococcal pathogenesis.
A new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies.

BACKGROUND Visceral leishmaniasis (VL) is transmitted by sand flies. Protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for VL. METHODS We used Lutzomyia longipalpis to transmit Leishmania infantum or Leishmania donovani to hamsters. Vector-initiated infections were monitored and compared with intracardiac infections. Body weights were recorded weekly. Organ parasite loads and parasite pick-up by flies were assessed in sick hamsters. RESULTS Vector-transmitted L. infantum and L. donovani caused ≥5-fold increase in spleen weight compared with uninfected organs and had geometric mean parasite loads (GMPL) comparable to intracardiac inoculation of 10(7)-10(8) parasites, although vector-initiated disease progression was slower and weight loss was greater. Only vector-initiated L. infantum infections caused cutaneous lesions at transmission and distal sites. Importantly, 45.6%, 50.0%, and 33.3% of sand flies feeding on ear, mouth, and testicular lesions, respectively, were parasite-positive. Successful transmission was associated with a high mean percent of metacyclics (66%-82%) rather than total GMPL (2.0 × 10(4)-8.0 × 10(4)) per midgut. CONCLUSIONS This model provides an improved platform to study initial immune events at the bite site, parasite tropism, and pathogenesis and to test drugs and vaccines against naturally acquired VL.
Inadvertent Subconjunctival Injection of a Dexamethasone Implant.

Delivery of a dexamethasone intravitreal implant (Ozurdex, Allergan) was planned for a man in his 60s with postsurgical cystoid macular edema. Best-corrected visual acuity was 20/60 OD and central subfield thickness was 553 μm. The injection was accidentally performed in the subconjonctival space (Figure, A). The device broke into 3 parts but it was not removed. Intraocular pressure did not exceed 17 mm Hg without treatment during a close follow-up, but 3 weeks later, the patient developed an endothelial decompensation. Best-corrected visual acuity dropped to 20/200 OD and the implant was surgically removed immediately. Bestcorrected visual acuity was 20/60 OD with a clear cornea by 15 days after removal of the implant and a combination of dimethicone drops and hyperosmotic sodium chloride drops. Another dexamethasone intravitreal implant was given 45 days after removal of the implant (visual acuity, 20/60 OD; central subfield thickness, 485 μm) and macular edema was noted to have resolved by 7 days after implantation (visual acuity, 20/30 OD; central subfield thickness, 305 μm).
The Radio to Gamma Ray Connection of EGRET Blazars: Correlation, Regression and Monte Carlo Analysis

Using a sample of 122 potential EGRET blazars, we find that there is a relationshp Lγ ∝ Lr0.079 as well as a correlation between αog and αro, and a correlation between Lr and αog. Through the use of Monte Carlo simulations, we discuss the validity of synchrotron self‐Compton and external Compton scattering models models in leading to the correlations we observe.
Peculiar monomeric interferon gammas, IFNγrel 1 and IFNγrel 2, in ginbuna crucian carp

The existence of fish‐specific isoforms of interferon (IFN)γ, known as IFNγ‐related (IFNγrel), has been reported in several fish species. However, comparisons with deduced amino acid sequences of known IFNγrels among several fish species have indicated significant differences at the C‐terminus basic amino acid continuous sequences, which indicate the existence of multiple IFNγrel isoforms. Two distinct cDNAs, encoding two IFNγrels, ifngrel 1 and ifngrel 2, were cloned from ginbuna crucian carp (Carassius auratus langsdorfii). Recombinant IFNγrel 1 and IFNγrel 2 have shown high antiviral activities against the lethal crucian carp hematopoietic necrosis virus. Both ligands exhibit biological activity as monomers despite the fact that the functional conformation of IFNγ is a homodimer. Both interferons have a high degree of sequence similarity, but differ in the C‐terminus region. In this region, IFNγrel 1 contains a functional nuclear localization sequence which induces the translocation of green fluorescent protein from the cytoplasm to the nucleus. IFNγrel 2 lacks this sequence. These results indicate that IFNγrel 1 and IFNγrel 2 are functional antiviral cytokines. These structurally related ligands play distinct antiviral roles through different intracellular translocation mechanisms. Thus, IFNγrels form a novel, distinct subtype included in type II IFNs. The cyprinid fish IFNγ subtype currently consists of four members, including two IFNγ isoforms and two distinct additional IFNγrel isoforms specific to the fish.
EQUINE ANTIHAPTEN ANTIBODY

Eight antigenically unique immunoglobulins have been identified in purified equine anti-p-azophenyl-β-lactoside (Lac) antibody isolated from a single horse. The Fc fragments of the γGa-, γGb-, γGc-, and -γA-globulins have been shown to possess unique antigenic determinants. Common γG- and γA-Fc fragment antigenic determinants, which were absent from the 10Sγ1- and γM-globulins, have also been observed. All antibody populations share two antigenically distinct light (B, L) chain variants. The association of anti-Lac antibody with the hapten p-(p-dimethylamino-benzeneazo)-phenyl-β-lactoside has been measured by equilibrium dialysis and by fluorescence quenching. A variation in the affinity of anti-Lac antibody for hapten has been observed. The affinity of antibody was unaltered by enzymatic removal of the Fc fragments by peptic digestion or dissociation of the two combining sites on the papain 3.5S Fab fragments, indicating that the observed heterogeneity of affinities was not a direct function of the heterogeneity in structure of the Fc fragments. Isolated heavy (A, H) chains of γA-anti-Lac antibody have been shown to have retamed affinity for Lac dye by equilibrium dialysis and by analytical ultracentrifugation, employing a combination of schlieren and absorption optics. The heavy (A, H) chains from two physically separable, antigenically distinct antibody populations, isolated from the same animal and having affinity for the same haptenic determinant, have been found to differ in their amino acid composition. Anti-Lac antibody light (B, L) chains have also been shown to be chemically heterogeneous, and contained populations of polypeptide chains possessing, and populations lacking methionine. The relevance of the observed structural heterogeneity of equine anti-Lac antibody to the problem of defining the mechanism of acquisition of immunological specificity is briefly discussed.
Pertussis resurgence: perspectives from the Working Group Meeting on pertussis on the causes, possible paths forward, and gaps in our knowledge.

The incidence of reported pertussis has steadily increased in the United States since the 1980s, with a striking increase observed since 2005 [1]. Provisional case counts in the United States for 2012 exceed 41 000, with 14 deaths among infants [2]. This resurgence in pertussis that has been seen in the United States and other countries [3] has caused considerable concern. On 6 March 2013, 64 experts in the field of pertussis vaccinology, from academia, government agencies, and pharmaceutical companies, met during the Working Group Meeting on Pertussis that was held in Bethesda, Maryland. This workshop offered a unique opportunity for experts to discuss possible causes of the resurgence in pertussis, the possible paths forward, and the remaining gaps in our knowledge. To take advantage of this collection of experts, 3 discussion sessions were held during the workshop to discuss (1) potential root cause(s) of the problem, (2) what interim solutions may exist, and (3) how the problem might be solved in the long term. At the end of the workshop, the experts agreed that use of the currently available vaccines is an important strategy but that longer-term solutions are necessary to more effectively control pertussis. No clear consensus was reached as to a single root cause of the problem nor did a clear long-term solution emerge. However, the group began to define gaps in knowledge, discussed hypotheses that could be tested, and suggested priorities for research and development.
Amyloid aggregation and deposition of human islet amyloid polypeptide at membrane interfaces

Amyloid deposition of human islet amyloid polypeptide (hIAPP) within the islets of Langerhans is a pathological feature of type 2 diabetes mellitus. Substantial evidence indicates that the membrane‐mediated aggregation and subsequent deposition of hIAPP are linked to dysfunction and death of pancreatic β‐cells, but the molecular processes of hIAPP deposition are poorly understood. In this study, we examined the membrane‐mediated aggregation and deposition of hIAPP at supported planar lipid bilayers with and without raft components (i.e. cholesterol and sphingomyelin) to provide insight into hIAPP‐induced membrane dysfunction. The adsorption of hIAPP onto the bilayers was studied using a quartz crystal microbalance with dissipation monitoring, which showed enhanced accumulation of the peptide onto the bilayer containing raft components. Microscope observations demonstrated the growth of the aggregates formed from the membrane‐adsorbed hIAPP. The examination of the membrane interfaces revealed that hIAPP aggregates retained the ability to associate with the membranes during the aggregation process, resulting in insertion of the aggregates into the bilayers. We also report the inhibitory effect of insulin on the hIAPP deposition. These findings demonstrate the aggregation of hIAPP at the membrane interfaces leading to amyloid deposits associated with the membrane and suggest a role for insulin in hIAPP deposition. A presumed mechanism regulating hIAPP deposition at the membrane interfaces is discussed.
Controversia en relación con el uso de bifosfonatos en pacientes con enfermedad renal

Los bifosfonatos son medicamentos antirreabsortivos gracias a su capacidad de alterar las funciones de los osteoclastos, en los que llegan tambien a inducir apoptosis. Otros beneficios terapeuticos de estos medicamentos son su accion antiinflamatoria e inhibidora de la formacion de placas arterioscleroticas. Clasicamente la presencia de alteraciones en la funcion renal ha sido una contraindicacion para su uso, pero evidencia reciente ha demostrado que con adecuado ajuste de su dosis, o seleccionando bifosfonatos con bajo perfil de toxicidad, alto grado de fijacion osea y a proteinas sericas, y alta remocion en la terapia dialitica podrian ser un arma terapeutica excelente en patologias que simultaneamente afecten los rinones y otros organos como el mieloma multiple, y en estados hiperfosfatemicos asociados a alto recambio oseo.