bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen detection for human immunodeficiency virus
Authors: Harry D J , Jennings M B , Yee J , Carlson J R
Published: June 2016

The recent development of enzyme immunoassay procedures for the direct determination of human immunodeficiency virus (HIV) antigens has been of significant benefit in both clinical and research applications. The historical development of HIV antigen assays as well as their current and future applications for use in the clinical microbiology laboratory are reviewed. A detailed description of selected commercially available assays is presented, and a comparison is made of various parameters, including sensitivity, specificity, and cost. The use of the HIV antigen assay as an alternative to the reverse transcriptase assay in virus culture applications is also discussed. In addition, the diagnostic and prognostic utility of the HIV antigen assay is considered for various patient groups, including neonatal, high-risk asymptomatic, seronegative, and seropositive patient populations. The use of the HIV antigen assay as an adjunct to anti-HIV antibody testing, as well as its utility in assessing the therapeutic efficacy of antiviral drug therapy, is discussed. The biology of HIV antigen expression and modulation of anti-HIV antibody titers during infection are also discussed in terms of two possible models.
Streptococcal M protein: molecular design and biological behavior
Authors: Fischetti V A
Published: June 2016

M protein is a major virulence determinant for the group A streptococcus by virtue of its ability to allow the organism to resist phagocytosis. Common in eucaryotes, the fibrillar coiled-coil design for the M molecule may prove to be a common motif for surface proteins in gram-positive organisms. This type of structure offers the organism several distinct advantages, ranging from antigenic variation to multiple functional domains. The close resemblance of this molecular design to that of certain mammalian proteins could help explain on a molecular level the formation of epitopes responsible for serological cross-reactions between microbial and mammalian proteins. Many of the approaches described in the elucidation of the M-protein structure may be applied for characterizing similar molecules in other microbial systems.
Clinical implications of positive blood cultures
Authors: Bryan C S
Published: June 2016

Positive blood cultures can be classified according to their veracity (true-positive or false-positive culture), clinical severity (inconsequential or life threatening), place of origin (community acquired or nosocomial), source (primary or secondary), duration (transient, intermittent, or continuous), pattern of occurrence (single episode, persistent, or recurrent), or intensity (high or low grade). In general, however, positive blood cultures identify a patient population at high risk of death. In my studies, patients with positive blood cultures were 12 times more likely to die during hospitalization than patients without positive blood cultures. Many bacteremias and fungemias occur in complicated clinical settings, and it appears that only about one-half of the deaths among affected patients are due directly to infection. Hence, it is appropriate to speak of "crude mortality" and "attributable mortality." Among hospitalized patients, recent trends include rising incidences of Staphylococcus aureus and coagulase-negative staphylococcal and enterococcal bacteremias and a dramatic increase in the incidence of fungemias. The diagnostic and therapeutic implications of blood cultures positive for specific microorganisms continue to evolve and are the subject of a large and growing medical literature.
Discovery and development of new antimicrobial agents
Authors: Gootz T D
Published: June 2016

The unprecedented growth in the number of new antibiotics over the past two decades has been the result of extensive research efforts that have exploited the growing body of knowledge describing the interactions of antibiotics with their targets in bacterial cells. Information gained from one class of antimicrobial agents has often been used to advance the development of other classes. In the case of beta-lactams, information on structure-activity relationships gleaned from penicillins and cephalosporins was rapidly applied to the cephamycins, monobactams, penems, and carbapenems in order to discover broad-spectrum agents with markedly improved potency. These efforts have led to the introduction of many new antibiotics that demonstrate outstanding clinical efficacy and improved pharmacokinetics in humans. The current review discusses those factors that have influenced the rapid proliferation of new antimicrobial agents, including the discovery of new lead structures from natural products and the impact of bacterial resistance development in the clinical setting. The development process for a new antibiotic is discussed in detail, from the stage of early safety testing in animals through phase I, II, and III clinical trials.
Statistical methods in microbiology
Authors: Ilstrup D M
Published: June 2016

Statistical methodology is viewed by the average laboratory scientist, or physician, sometimes with fear and trepidation, occasionally with loathing, and seldom with fondness. Statistics may never be loved by the medical community, but it does not have to be hated by them. It is true that statistical science is sometimes highly mathematical, always philosophical, and occasionally obtuse, but for the majority of medical studies it can be made palatable. The goal of this article has been to outline a finite set of methods of analysis that investigators should choose based on the nature of the variable being studied and the design of the experiment. The reader is encouraged to seek the advice of a professional statistician when there is any doubt about the appropriate method of analysis. A statistician can also help the investigator with problems that have nothing to do with statistical tests, such as quality control, choice of response variable and comparison groups, randomization, and blinding of assessment of response variables.
Coryneform bacteria in infectious diseases: clinical and laboratory aspects
Authors: Coyle M B , Lipsky B A
Published: June 2016

Coryneform isolates from clinical specimens frequently cannot be identified by either reference laboratories or research laboratories. Many of these organisms are skin flora that belong to a large number of taxonomic groups, only 40% of which are in the genus Corynebacterium. This review provides an update on clinical presentations, microbiological features, and pathogenic mechanisms of infections with nondiphtheria Corynebacterium species and other pleomorphic gram-positive rods. The early literature is also reviewed for a few coryneforms, especially those whose roles as pathogens are controversial. Recognition of newly emerging opportunistic coryneforms is dependent on sound identification schemes which cannot be developed until cell wall analyses and nucleic acid studies have defined the taxonomic groups and all of the reference strains within each taxon have been shown by molecular methods to be authentic members. Only then can reliable batteries of biochemical tests be selected for distinguishing each taxon.
Branhamella catarrhalis: an organism gaining respect as a pathogen
Authors: Catlin B W
Published: June 2016

Branhamella catarrhalis was formerly regarded as a common, essentially harmless inhabitant of the pharynx. This misapprehension was caused, in part, by confusion with another pharyngeal resident, Neisseria cinerea. The two organisms can now be differentiated by the positive reactions of B. catarrhalis in tests for nitrate reduction and hydrolysis of tributyrin and DNase. B. catarrhalis is currently recognized as the third most frequent cause of acute otitis media and acute sinusitis in young children. It often causes acute exacerbations of chronic bronchopulmonary disease in older or immunocompromised adults and is incriminated occasionally in meningitis, endocarditis, bacteremia, conjunctivitis, keratitis, and urogenital infections. Virulence-associated factors, such as pili, capsules, outer membrane vesicles, iron acquisition proteins, histamine-synthesizing ability, resistance to the bactericidal action of normal human serum, and binding to the C1q complement component, have been identified in some strains. beta-Lactamase producing strains, first detected in 1976, have risen to approximately 75% worldwide. Thus far, however, practically all American strains of B. catarrhalis remain susceptible to alternative antibiotics. A possible selective advantage of recent isolates is their reportedly heightened tendency for adherence to oropharyngeal cells from patients with chronic bronchopulmonary disease.
Is there a role for lactobacilli in prevention of urogenital and intestinal infections?
Authors: Reid G , Bruce A W , McGroarty J A , Cheng K J , Costerton J W
Published: June 2016

This review describes the importance of microbial adhesion in the ecology of the urogenital and intestinal tracts and the influence of host and microbial factors in bacterial interference. In a recent revival of interest in bacterial interference, lactobacillus administration has been studied as a means of treating and preventing disease. Although evidence is conflicting, Lactobacillus acidophilus appears to be involved in beneficial antagonistic and cooperative reactions that interfere with establishment of pathogens in the gastrointestinal tract. The mechanisms of action are believed to involve competitive exclusion and production of inhibitory substances, including bacteriocins. These characteristics, as well as demonstrated adherence abilities in vitro, led to selection of certain Lactobacillus strains for clinical studies of cystitis. Weekly intravaginal Lactobacillus therapy reduced the recurrence rate of uncomplicated lower urinary tract infections in women. Use of Lactobacillus strains resistant to Nonoxynol-9, a spermicide that kills members of the protective normal vaginal flora, may have potential for use in women with recurrent cystitis using this contraceptive agent. In veterinary studies, bacterial interference by administration of probiotics has also been beneficial in disease prevention in animals. Carefully selected bacterial mixtures integrate with the gastrointestinal flora of the animals and can confer disease resistance and improve physiological function. Additional human and animal trials are needed to determine the practical, long-term usefulness of bacterial interference as a protective mechanism against infectious diseases.
The dengue viruses
Authors: Henchal E A , Putnak J R
Published: June 2016

Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made.
Virulence factors in Escherichia coli urinary tract infection
Authors: Johnson J R
Published: June 2016

Uropathogenic strains of Escherichia coli are characterized by the expression of distinctive bacterial properties, products, or structures referred to as virulence factors because they help the organism overcome host defenses and colonize or invade the urinary tract. Virulence factors of recognized importance in the pathogenesis of urinary tract infection (UTI) include adhesins (P fimbriae, certain other mannose-resistant adhesins, and type 1 fimbriae), the aerobactin system, hemolysin, K capsule, and resistance to serum killing. This review summarizes the virtual explosion of information regarding the epidemiology, biochemistry, mechanisms of action, and genetic basis of these urovirulence factors that has occurred in the past decade and identifies areas in need of further study. Virulence factor expression is more common among certain genetically related groups of E. coli which constitute virulent clones within the larger E. coli population. In general, the more virulence factors a strain expresses, the more severe an infection it is able to cause. Certain virulence factors specifically favor the development of pyelonephritis, others favor cystitis, and others favor asymptomatic bacteriuria. The currently defined virulence factors clearly contribute to the virulence of wild-type strains but are usually insufficient in themselves to transform an avirulent organism into a pathogen, demonstrating that other as-yet-undefined virulence properties await discovery. Virulence factor testing is a useful epidemiological and research tool but as yet has no defined clinical role. Immunological and biochemical anti-virulence factor interventions are effective in animal models of UTI and hold promise for the prevention of UTI in humans.
Cryptosporidiosis
Authors: Current W L , Garcia L S
Published: June 2016

Before 1982, only eight case reports of human cryptosporidiosis and fewer than 30 papers on Cryptosporidium spp. appeared in the biomedical literature. At that time, cryptosporidiosis was thought to be an infrequent infection in animals and rarely an opportunistic infection in humans. The concept of Cryptosporidium spp. as pathogens has changed dramatically within the past 8 years because of improved diagnostic techniques, increased awareness within the biomedical community, and the development of basic research programs in numerous laboratories. Presently, greater than 1,000 publications including over 400 case reports in the biomedical literature address Cryptosporidium spp. and cryptosporidiosis. Cryptosporidium parvum is now thought to be one of the three most common enteropathogens causing diarrheal illness in humans worldwide, especially in developing countries. It is likely that cryptosporidiosis was previously included in the 25 to 35% of diarrheal illness with unknown etiology. Because of the severity and length of diarrheal illness and because no effective therapy has been identified, cryptosporidiosis is one of the most ominous infections associated with AIDS. The role of C. parvum as an enteropathogen is well established; documentation of its role as a cause of hepatobiliary and respiratory diseases is now appearing in the literature. Our present understanding of the natural history, epidemiology, biology, and immunology of Cryptosporidium spp. as well as the clinical features, pathogenicity, and treatment of cryptosporidiosis are reviewed here.
Infectious diseases associated with complement deficiencies
Authors: Figueroa J E , Densen P
Published: June 2016

The complement system consists of both plasma and membrane proteins. The former influence the inflammatory response, immune modulation, and host defense. The latter are complement receptors, which mediate the cellular effects of complement activation, and regulatory proteins, which protect host cells from complement-mediated injury. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. Four aspects of the complement cascade are critical to its function and regulation: (i) activation of the classical pathway, (ii) activation of the alternative pathway, (iii) C3 convertase formation and C3 deposition, and (iv) membrane attack complex assembly and insertion. In general, mechanisms evolved by pathogenic microbes to resist the effects of complement are targeted to these four steps. Because individual complement proteins subserve unique functional activities and are activated in a sequential manner, complement deficiency states are associated with predictable defects in complement-dependent functions. These deficiency states can be grouped by which of the above four mechanisms they disrupt. They are distinguished by unique epidemiologic, clinical, and microbiologic features and are most prevalent in patients with certain rheumatologic and infectious diseases. Ethnic background and the incidence of infection are important cofactors determining this prevalence. Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies.
Recent advances in the study of the taxonomy, pathogenicity, and infectious syndromes associated with the genus Aeromonas
Authors: Janda J M
Published: June 2016

Over the past decade, the emergence of Aeromonas species as bona fide human pathogens and their probable role as etiologic agents of bacterial gastroenteritis have resulted in an explosion of scientific interest in the genus. Major accomplishments occurring in this field during that interval include a more refined taxonomy, identification of new cell-associated factors (surface layers, pili), and the molecular analysis of selected extracellular gene products that may play a critical role in pathogenesis (hemolysins, enterotoxins). This review provides an updated overview of recent systematic, clinical, and pathophysiologic advances and defines key areas of medical and scientific interest in which major questions remain unanswered.
Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain
Authors: Major E O , Amemiya K , Tornatore C S , Houff S A , Berger J R
Published: June 2016

Studies of the pathogenesis and molecular biology of JC virus infection over the last two decades have significantly changed our understanding of progressive multifocal leukoencephalopathy, which can be described as a subacute viral infection of neuroglial cells that probably follows reactivation of latent infection rather than being the consequence of prolonged JC virus replication in the brain. There is now sufficient evidence to suggest that JC virus latency occurs in kidney and B cells. However, JC virus isolates from brain or kidney differ in the regulatory regions of their viral genomes which are controlled by host cell factors for viral gene expression and replication. DNA sequences of noncoding regions of the viral genome display a certain heterogeneity among isolates from brain and kidney. These data suggest that an archetypal strain of JC virus exists whose sequence is altered during replication in different cell types. The JC virus regulatory region likely plays a significant role in establishing viral latency and must be acted upon for reactivation of the virus. A developing hypothesis is that reactivation takes place from latently infected B lymphocytes that are activated as a result of immune suppression. JC virus enters the brain in the activated B cell. Evidence for this mechanism is the detection of JC virus DNA in peripheral blood lymphocytes and infected B cells in the brains of patients with progressive multifocal leukoencephalopathy. Once virus enters the brain, astrocytes as well as oligodendrocytes support JC virus multiplication. Therefore, JC virus infection of neuroglial cells may impair other neuroglial functions besides the production and maintenance of myelin. Consequently our increased understanding of the pathogenesis of progressive multifocal leukoencephalopathy suggests new ways to intervene in JC virus infection with immunomodulation therapies. Perhaps along with trials of nucleoside analogs or interferon administration, this fatal disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols.
Giardiasis
Authors: Wolfe M S
Published: June 2016

Giardiasis is one of the most common pathogenic intestinal protozoal infections worldwide. Giardia lamblia is the most frequently identified etiologic agent in outbreaks associated with the ingestion of surface water, often due to ineffective filtration or pretreatment. In addition to humans, other sources of infection include beavers, perhaps muskrats, and possibly domestic animals. A low infecting dose (10 to 25 cysts) is reported to be sufficient to produce human infection. Clinical manifestations range from asymptomatic to a transient or persistent acute stage, with steatorrhea, intermittent diarrhea, and weight loss, or to a subacute or chronic stage that can mimic gallbladder or peptic ulcer disease. Diagnosis is usually based on repeated stool examinations but examination of duodenal fluid or biopsy material may also be necessary. Enzyme immunoassay or indirect immunofluorescence methods for direct detection of antigen or whole organisms in clinical specimens have also been developed. These tests are reported to be more sensitive than routine stool examination. Demonstration of serum immunoglobulin M and G antibodies may help differentiate recent from past infection or help detect recurrence in individuals who have been treated previously. Serum immunoglobulin A levels may be a useful indicator of exposure in waterborne outbreaks of diarrhea. Drugs available for treatment within the United States include metronidazole, quinacrine hydrochloride, and furazolidone.
Laboratory methods for early detection of human immunodeficiency virus type 1 in newborns and infants
Authors: Sison A V , Campos J M
Published: June 2016

Cumulative data on serological testing of newborns and infants have shown that (i) maternal and newborn anti-HIV-1 IgG titers are high at delivery, which may explain the persistence of antibody in the infants of seropositive mothers; (ii) in some situations, serial HIV-1 antibody testing may identify infected infants; and (iii) detection of anti-HIV-1 IgA or IgM is specific for infection but the sensitivity of this assay may be compromised in certain situations, such as when infected infants are hypogammaglobulinemic or when the rise and fall of HIV-1-specific IgM synthesis following acute infection has been completed before delivery of the infant. Cumulative data on PCR, viral culture, and tests for antigen in newborns and infants have shown that (i) among all age groups, viral culture is probably the most specific test available for detection of HIV-1, as PCR and the p24 antigen test may (though rarely) give false-positive results; (ii) the sensitivity of these tests increases in the order of antigen, culture, and PCR, with relatively insensitive results in the first 3 months of life for all of these tests; (iii) the sensitivity of all of these tests improves and approximates 90 to 100% when infants over 6 months of age are tested; and (iv) data regarding the sensitivity, specificity, and usefulness of these virological assays in infants under 3 months of age are very scant and inconclusive.
Adenoviruses in the immunocompromised host
Authors: Hierholzer J C
Published: June 2016

Adenoviruses are among the many pathogens and opportunistic agents that cause serious infection in the congenitally immunocompromised, in patients undergoing immunosuppressive treatment for organ and tissue transplants and for cancers, and in human immunodeficiency virus-infected patients. Adenovirus infections in these patients tend to become disseminated and severe, and the serotypes involved are clustered according to the age of the patient and the nature of the immunosuppression. Over 300 adenovirus infections in immunocompromised patients, with an overall case fatality rate of 48%, are reviewed in this paper. Children with severe combined immunodeficiency syndrome and other primary immunodeficiencies are exposed to the serotypes of subgroups B and C that commonly infect young children, and thus their infections are due to types 1 to 7 and 31 of subgenus A. Children with bone marrow and liver transplants often have lung and liver adenovirus infections that are due to an expanded set of subgenus A, B, C, and E serotypes. Adults with kidney transplants have viruses of subgenus B, mostly types 11, 34, and 35, which cause cystitis. This review indicates that 11% of transplant recipients become infected with adenoviruses, with case fatality rates from 60% for bone marrow transplant patients to 18% for renal transplant patients. Patients with AIDS become infected with a diversity of serotypes of all subgenera because their adult age and life-style expose them to many adenoviruses, possibly resulting in antigenically intermediate strains that are not found elsewhere. Interestingly, isolates from the urine of AIDS patients are generally of subgenus B and comprise types 11, 21, 34, 35, and intermediate strains of these types, whereas isolates from stool are of subgenus D and comprise many rare, new, and intermediate strains that are untypeable for practical purposes. It has been estimated that adenoviruses cause active infection in 12% of AIDS patients and that 45% of these infections terminate in death within 2 months. In all immunocompromised patients, generalized illness involving the central nervous system, respiratory system, hepatitis, and gastroenteritis usually have a fulminant course and result in death. Treatments for adenovirus infections are of little proven value, although certain purine and pyrimidine analogs have shown beneficial effects in vitro and may be promising drugs.
Hepatitis B virus infection and primary hepatocellular carcinoma
Authors: Feitelson M
Published: June 2016

For many years, epidemiological studies have demonstrated a strong link between chronic hepatitis B virus (HBV) infection and the development of primary hepatocellular carcinoma (PHC). Other hepatocarcinogens such as hepatitis C virus and aflatoxin also contribute to hepatocarcinogenesis either in conjunction with HBV infection or alone. Cellular and molecular biological studies are providing explanations for the HBV-PHC relationship, and models are now being formulated to further test the relative importance of various factors such as viral DNA integration, activation of oncogenes, genetic instability, loss of tumor suppressor genes, and trans-activating properties of HBV to the pathogenesis of PHC. Further research will probably define more than a single mechanism whereby chronic HBV infection results in PHC.
Automated systems for identification of microorganisms
Authors: Stager C E , Davis J R
Published: June 2016

Automated instruments for the identification of microorganisms were introduced into clinical microbiology laboratories in the 1970s. During the past two decades, the capabilities and performance characteristics of automated identification systems have steadily progressed and improved. This article explores the development of the various automated identification systems available in the United States and reviews their performance for identification of microorganisms. Observations regarding deficiencies and suggested improvements for these systems are provided.
Dysregulation of strongyloidiasis: a new hypothesis
Authors: Genta R M
Published: June 2016

Few other human parasites are associated with such a diverse spectrum of clinical manifestations as Strongyloides stercoralis, yet the basic biological behavior of this unusually versatile worm, particularly with respect to its ability to cause severe disseminated disease in certain hosts, is poorly understood. The current uncritical acceptance of the theory that cell-mediated immunity controls autoinfection has stifled research in other directions. After reviewing what is and is not known about the parasite's behavior in its host, this article explores some of the mechanisms that could be involved in the regulation of the parasite population. Taking the provocative viewpoint that the parasite, not the host, is mainly responsible for the maintenance of a balanced relationship between the two, I propose a new theory that corticosteroids may act on the intraintestinal larvae as molting hormones and directly promote the development of disseminated disease.
Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance
Authors: Speer B S , Shoemaker N B , Salyers A A
Published: June 2016

Tetracycline has been a widely used antibiotic because of its low toxicity and broad spectrum of activity. However, its clinical usefulness has been declining because of the appearance of an increasing number of tetracycline-resistant isolates of clinically important bacteria. Two types of resistance mechanisms predominate: tetracycline efflux and ribosomal protection. A third mechanism of resistance, tetracycline modification, has been identified, but its clinical relevance is still unclear. For some tetracycline resistance genes, expression is regulated. In efflux genes found in gram-negative enteric bacteria, regulation is via a repressor that interacts with tetracycline. Gram-positive efflux genes appear to be regulated by an attenuation mechanism. Recently it was reported that at least one of the ribosome protection genes is regulated by attenuation. Tetracycline resistance genes are often found on transmissible elements. Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and self-transmissible chromosomal elements (conjugative transposons). One class of conjugative transposon, originally found in streptococci, can transfer itself from streptococci to a variety of recipients, including other gram-positive bacteria, gram-negative bacteria, and mycoplasmas. Another class of conjugative transposons has been found in the Bacteroides group. An unusual feature of the Bacteroides elements is that their transfer is enhanced by preexposure to tetracycline. Thus, tetracycline has the double effect of selecting for recipients that acquire a resistance gene and stimulating transfer of the gene.
Paracoccidioidomycosis: an update
Authors: Brummer E , Castaneda E , Restrepo A
Published: June 2016

This review summarizes knowledge on various aspects of paracoccidioidomycosis. Mycelial propagules, chlamydospores, and arthroconidia exhibit thermal dimorphism; arthroconidia are infectious in animals and, by electron microscopy, appear well provided for survival. The mycelial-to-yeast-phase transformation requires a strict control of glucan synthesis probably mediated by membrane enzymes. Hormonal influences on the transformation of the fungus (mycelium or conidium to yeast phase) have been demonstrated. Estrogen-binding proteins have been detected in the fungal cytosol, and during the transformation novel proteins are produced as a result of estradiol incorporation. Clinical forms have been better defined on the basis of better experimental models. Emphasis has been placed on the lungs as the portal of entry and on the existence of silent pulmonary infections. A specific Paracoccidioides brasiliensis antigen, the 43-kDa glycoprotein (Gp43), has been identified, characterized, and cloned. This has led to improved reproducibility and specificity of serologic tests. The depression of cell-mediated immune responses has been associated with severe disease in humans and in the experimental host. T-cell subsets in patients' tissues were characterized by means of monoclonal antibodies, and a reduced CD4/CD8 ratio was demonstrated. This has been related to alterations in lymphokine and tumor necrosis factor production, production of antigen-antibody complexes, etc. Amphotericin B has provided effective therapy. Azole derivatives have also improved prognosis and facilitated therapy. Itraconazole is presently the drug of choice, yet incapacitating sequelae (mainly pulmonary fibrosis) still constitute major problems.
Delta hepatitis: molecular biology and clinical and epidemiological features
Authors: Polish L B , Gallagher M , Fields H A , Hadler S C
Published: June 2016

Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection.
Markers predicting progression of human immunodeficiency virus-related disease
Authors: Tsoukas C M , Bernard N F
Published: June 2016

Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression.
PCR-Based Serotyping of Streptococcus pneumoniae from Culture-Negative Specimens: Novel Primers for Detection of Serotypes within Serogroup 18
Authors: Tanmoy Arif M. , Saha Senjuti , Darmstadt Gary L. , Whitney Cynthia G. , Saha Samir K.
Published: June 2016

Six multiplex-compatible PCR primers were designed to distinguish
Streptococcus pneumoniae
serotypes within serogroup 18 from culturable/nonculturable pneumococcal specimens, with no cross-reactivity with other serotypes and respiratory organisms. These primers will aid in the generation of better data on vaccine/nonvaccine serotypes in invasive and carriage pneumococcal surveillance and contribute to future vaccine formulation and impact studies.
Time-Dependent Rate Phenomenon in Viruses
Authors: Aiewsakun Pakorn , Katzourakis Aris
Published: June 2016

Among the most fundamental questions in viral evolutionary biology are how fast viruses evolve and how evolutionary rates differ among viruses and fluctuate through time. Traditionally, viruses are loosely classed into two groups: slow-evolving DNA viruses and fast-evolving RNA viruses. As viral evolutionary rate estimates become more available, it appears that the rates are negatively correlated with the measurement timescales and that the boundary between the rates of DNA and RNA viruses might not be as clear as previously thought. In this study, we collected 396 viral evolutionary rate estimates across almost all viral genome types and replication strategies, and we examined their rate dynamics. We showed that the time-dependent rate phenomenon exists across multiple levels of viral taxonomy, from the Baltimore classification viral groups to genera. We also showed that, by taking the rate decay dynamics into account, a clear division between the rates of DNA and RNA viruses as well as reverse-transcribing viruses could be recovered. Surprisingly, despite large differences in their biology, our analyses suggested that the rate decay speed is independent of viral types and thus might be useful for better estimation of the evolutionary time scale of any virus. To illustrate this, we used our model to reestimate the evolutionary timescales of extant lentiviruses, which were previously suggested to be very young by standard phylogenetic analyses. Our analyses suggested that these viruses are millions of years old, in agreement with paleovirological evidence, and therefore, for the first time, reconciled molecular analyses of ancient and extant viruses.

IMPORTANCE
This work provides direct evidence that viral evolutionary rate estimates decay with their measurement timescales and that the rate decay speeds do not differ significantly among viruses despite the vast differences in their molecular features. After adjustment for the rate decay dynamics, the division between the rates of double-stranded DNA (dsDNA), single-stranded RNA (ssRNA), and ssDNA/reverse-transcribing viruses could be seen more clearly than before. Our results provide a guideline for further improvement of the molecular clock. As a demonstration of this, we used our model to reestimate the timescales of modern lentiviruses, which were previously thought to be very young, and concluded that they are millions of years old. This result matches the estimate from paleovirological analyses, thus bridging the gap between ancient and extant viral evolutionary studies.
Recent volcanic resurfacing of Venusian craters
Authors: Whitten Jennifer L. , Campbell Bruce A.
Published: June 2016

Ejecta from impact craters on Venus are a major source of fine-grained materials across the planet, and crater spatial distribution has been studied as a guide to the relative age and resurfacing rates of large regions. Of particular interest is the potential intersection of distal crater deposits and tesserae, highly deformed landforms that may be the oldest materials on Venus. The composition of tesserae is unknown, but is key to understanding whether water played a role in crustal differentiation. Thus, tesserae are ideal sites for future landed missions to identify possible felsic materials, but the short lifespan of surface landers means that efforts must be made to avoid contaminating surface materials from craters. Here we develop a method to detect distal crater ejecta on tessera terrain across Venus using NASA Magellan radar data. Our results show that fine-grained ejecta are unevenly distributed in the tesserae with respect to nearby craters. Many tesserae within a few hundred kilometers of plains craters do not have evidence for thick (>5–10 cm) mantling material, indicating that eolian or mass-wasting processes have moved the debris off the highland ridge slopes. At Sudenitsa Tesserae, within the young Beta-Atla-Themis region, we observe a radar signature of mantling debris, but there is no apparent source crater to which this material can be traced. We infer that the source crater has been resurfaced by volcanic activity within the past 80 m.y., and suggest that similar fine-grained ejecta deposits may have built up over time in other tesserae across Venus.
Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages
Authors: Anderson Mark J , Kwong Christina A , Atieh Mohammed , Pappas Sam G
Published: June 2016

Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies.
5-Fluorouracil-induced acute reversible heart failure not explained by coronary spasms, myocarditis or takotsubo: lessons from MRI
Authors: Fakhri Yama , Dalsgaard Morten , Nielsen Dorte , Lav Madsen Per
Published: June 2016

A 69-year-old woman presented with arterial hypotension, pulmonary oedema and a severely depressed left ventricular ejection fraction (LVEF) of 25% only 3 days after having received her first treatment for colorectal cancer with 5-fluorouracil (5-FU)-based therapy. The ECG demonstrated widespread ST-segment depression and echocardiography showed uniform hypokinesia of all left ventricular (LV) myocardial segments without signs of regional LV ballooning. Coronary angiography was normal and the patient gained full recovery after receiving treatment with heart failure medication. Interestingly, cardiac MRI scan 9 days later showed a normal LVEF with signs of neither myocardial oedema nor necrosis. Despite the high therapeutic efficacy of 5-FU in treatment of colorectal cancer, it is associated with undesired cardiac toxicities including coronary spasms, toxic inflammation and takotsubo cardiomyopathy. However, our patient did not fulfil the diagnostic criteria for the aforementioned complications. Based on this case report, we discuss alternative mechanisms including myocardial adenosine triphosphate depletion suggested from animal experiments.
Isolated bilateral inguinal lymphadenopathy in the absence of other symptoms, due to LGV in known HIV-positive MSM: is it more common than we think?
Authors: Cherif Soumeya , Yoganathan Kathir , Danino Susannah
Published: June 2016

The current resurgence of lymphogranuloma venereum (LGV) has drawn most attention to its potential for causing proctitis; however, this case highlights the need for awareness of LGV as a cause of isolated painful bilateral inguinal lymphadenopathy in a high-risk population and the importance of routine screening for LGV. We describe a case of a 37-year-old HIV positive man, in the population of men who have sex with men (MSM) who presented with bilateral enlarged inguinal lymph nodes and no other symptoms or signs. Urine nucleic acid amplification test was positive for chlamydia LGV-specific DNA. Tests from other sites were negative.
Diagnostic challenges in acromioclavicular septic arthritis
Authors: Williams Mark
Published: June 2016

A 69-year-old man with Klinefelter's syndrome presented with a painful shoulder and staphylococcal sepsis. He received intravenous antibiotics while investigations were performed to locate the source of infection. MRI demonstrated infection in the acromioclavicular joint (ACJ). The patient clinically improved and a further 5 weeks of oral antibiotics were given. He remained asymptomatic at 2-year follow-up. Although ACJ septic arthritis is rare, independent of immune-competent status, a high index of suspicion is essential for prompt diagnosis. The condition presents additional diagnostic challenges due to unfamiliarity, the challenges of interpreting imaging, desire for radiological guided arthrocentesis and low volume aspirates. Overcoming these pitfalls is essential to avoid significant morbidity and mortality.
Clinical outcomes of a scapular-focused treatment in patients with subacromial pain syndrome: a systematic review
Authors: Reijneveld Elja A E , Noten Suzie , Michener Lori A , Cools Ann , Struyf Filip
Published: June 2016

Objective

To systematically review the literature on the clinical outcomes of scapular-focused treatments in participants with subacromial pain syndrome (SPS).

Design

Systematic literature review. Studies were appraised by two reviewers using the Physiotherapy Evidence Database (PEDro) scale, and a best-evidence synthesis was performed.

Data sources

The literature search was conducted in the databases PubMed, Embase and Cinahl up to February 2015.

Eligibility criteria for selecting studies

Randomised controlled trials evaluating the clinical outcomes of a physiotherapeutic scapular-focused treatment in participants with SPS.

Results

Four studies were included describing various scapular-focused interventions, including scapular-focused exercise therapy, scapular mobilisation and scapular taping. All included studies had a PEDro score of 6 or higher, indicating low risk of bias. There was moderate evidence that scapular-focused treatment compared with other physiotherapeutic treatment is effective in improving scapular muscle strength in participants with SPS. Conflicting evidence was found for improvements in pain, function and clinical measures of scapular positioning. No evidence was found for improvements in shoulder range of motion or rotator cuff muscle strength.

Conclusions

There is some support for the use of scapular-focused exercise therapy in patients with SPS. Owing to the low number of studies, no firm conclusions can be drawn. Therefore, more randomised controlled trials are needed to determine the clinical outcomes of scapular-focused exercise therapy, scapular mobilisation techniques and scapular taping in patients with SPS.