bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chagas’ Disease and the Autoimmunity Hypothesis
Authors: Kierszenbaum Felipe 
Published: October 2018

SUMMARYThe notion that the pathology of Chagas’ disease has an autoimmune component was initially based on the finding of circulating antibodies binding heart tissue antigens in patients and mice chronically infected with Trypanosoma cruzi. Later, T lymphocytes reactive with heart or nerve tissue antigens were found in chagasic mice and patients, extending the concept to include cell-mediated immunity. However, there is disagreement about whether the observed immunologic autoreactivities are triggered by T. cruzi epitopes and then affect host tissue antigens by virtue of molecular mimicry or are elicited by host antigens exposed to lymphocytes after tissue damage caused by the parasite. There is also disagreement about the relevance of immunologic autoreactivities to the pathogenesis of Chagas’ disease because of the lack of reproducibility of some key reports supporting the autoimmunity hypothesis, conflicting data from independent laboratories, conclusions invalidated by advances in our understanding of the immunologic mechanisms underlying cell lysis, and, last but not least, a lack of direct, incontrovertible evidence that cross-reacting antibodies or autoreactive cells mediate the typical pathologic changes associated with human Chagas’ disease. The data and views backing and questioning the autoimmunity hypothesis for Chagas’ disease are summarized in this review.
Resistance of Human Cytomegalovirus to Antiviral Drugs
Authors: Erice Alejo 
Published: October 2018

SUMMARY
Resistance of cytomegalovirus (CMV) to antiviral agents is a well-recognized phenomenon that has been observed in the laboratory and in the clinical setting. Infections caused by antiviral-resistant CMV have been found exclusively among immunocompromised individuals, including patients with AIDS, bone marrow and solid-organ transplant recipients, and patients with hematologic malignancies, and in individuals with primary immunodeficiencies. The majority of these infections have been described to occur in patients with AIDS receiving prolonged antiviral therapy for CMV end-organ disease. Antiviral agents currently licensed for the treatment of CMV infections include ganciclovir, foscarnet, and cidofovir. Resistance of CMV to ganciclovir is related to mutations in the UL97 region of the viral genome and/or mutations in the viral DNA polymerase. Resistance to foscarnet and cidofovir is associated with mutations in the viral DNA polymerase. Antiviral susceptibility of CMV strains containing DNA polymerase mutations is dependent on the region of the DNA polymerase where the mutations are located. Some DNA polymerase mutant viruses are cross-resistant to ganciclovir, foscarnet, and cidofovir. The recognition that specific UL97 and UL54 mutations are associated with resistance to antiviral agents has led to the development of molecular methods for detection of mutant viruses. This article reviews the mechanisms of resistance of CMV to antiviral agents, the laboratory methods for detection of resistant CMV, and the clinical aspects of infections caused by antiviral-resistant CMV.
Acquisition, Transport, and Storage of Iron by Pathogenic Fungi
Authors: Howard Dexter H. 
Published: October 2018

SUMMARY
Iron is required by most living systems. A great variety of means of acquisition, avenues of uptake, and methods of storage are used by pathogenic fungi to ensure a supply of the essential metal. Solubilization of insoluble iron polymers is the first step in iron assimilation. The two methods most commonly used by microorganisms for solubilization of iron are reduction and chelation. Reduction of ferric iron to ferrous iron by enzymatic or nonenzymatic means is a common mechanism among pathogenic yeasts. Under conditions of iron starvation, many fungi synthesize iron chelators known as siderophores. Two classes of compounds that function in iron gathering are commonly observed: hydroxamates and polycarboxylates. Two major responses to iron stress in fungi are a high-affinity ferric iron reductase and siderophore synthesis. Regulation of these two mechanisms at the molecular level has received attention. Uptake of siderophores is a diverse process, which varies among the different classes of compounds. Since free iron is toxic, it must be stored for further metabolic use. Polyphosphates, ferritins, and siderophores themselves have been described as storage molecules. The iron-gathering mechanisms used by a pathogen in an infected host are largely unknown and can only be posited on the basis of in vitro studies at present.
Plant Products as Antimicrobial Agents
Authors: Cowan Marjorie Murphy 
Published: October 2018

SUMMARY
The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.
Potential Role of Phospholipases in Virulence and Fungal Pathogenesis
Authors: Ghannoum Mahmoud A. 
Published: October 2018

SUMMARY
Microbial pathogens use a number of genetic strategies to invade the host and cause infection. These common themes are found throughout microbial systems. Secretion of enzymes, such as phospholipase, has been proposed as one of these themes that are used by bacteria, parasites, and pathogenic fungi. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus, has gained credence recently. In this review, data implicating phospholipase as a virulence factor in C. albicans, Candida glabrata, C. neoformans, and A. fumigatus are presented. A detailed description of the molecular and biochemical approaches used to more definitively delineate the role of phospholipase in the virulence of C. albicans is also covered. These approaches resulted in cloning of three genes encoding candidal phospholipases (caPLP1, caPLB2, and PLD). By using targeted gene disruption, C. albicans null mutants that failed to secrete phospholipase B, encoded by caPLB1, were constructed. When these isogenic strain pairs were tested in two clinically relevant murine models of candidiasis, deletion of caPLB1 was shown to lead to attenuation of candidal virulence. Importantly, immunogold electron microscopy studies showed that C. albicans secretes this enzyme during the infectious process. These data indicate that phospholipase B is essential for candidal virulence. Although the mechanism(s) through which phospholipase modulates fungal virulence is still under investigations, early data suggest that direct host cell damage and lysis are the main mechanisms contributing to fungal virulence. Since the importance of phospholipases in fungal virulence is already known, the next challenge will be to utilize these lytic enzymes as therapeutic and diagnostic targets.
Drug Resistance in Human Helminths: Current Situation and Lessons from Livestock
Authors: Geerts S. , Gryseels B. 
Published: October 2018

SUMMARYIn this review the available reports on drug resistance in human helminths, particularly hookworms and schistosomes, are critically analyzed. The experiences with helminths of livestock are then reviewed, in particular the factors contributing to the development of anthelmintic resistance, the mechanisms and genetics of resistance to various anthelmintic classes, and the methods available for detection. These experiences appear to be worryingly similar and relevant to the potential development of drug resistance in human helminths. Recommendations to reduce its risks are suggested.
Worldwide
Haemophilus influenzae
Type b Disease at the Beginning of the 21st Century: Global Analysis of the Disease Burden 25 Years after the Use of the Polysaccharide Vaccine and a Decade after the Advent of Conjugates
Authors: Peltola Heikki 
Published: October 2018

SUMMARY
Vaccination against Haemophilus influenzae type b (Hib) diseases began a quarter of a century ago with a polysaccharide vaccine; this vaccine was followed by four different conjugates 10 years later. In this review, the burden of global Hib disease is quantified following this 25-year period of vaccine availability to determine the potential impact of conjugate vaccines. This task was accomplished by analysis of data available in 10 languages in 75 geographical regions of over 50 countries. All severe Hib diseases, not only meningitis, were characterized, and special attention was paid to the most vulnerable age group, i.e., children aged 0 to 4 years. Prior to vaccination, the weighted worldwide incidence of meningitis in patients younger than 5 years was 57/100,000, and for all Hib diseases except nonbacteremic pneumonia, it was 71/100,000, indicating 357,000 and 445,000 cases per year, respectively. At least 108,500 of these children died. For all age groups combined, there were 486,000 cases of Hib disease, excluding pneumonia, with 114,200 deaths and probably an equal number of sequelae per annum. If the figures for nonbacteremic pneumonia are included, a conservative estimate is that over 2.2 million cases of infection and 520,000 deaths from Hib disease occurred worldwide, but the true numbers might have been greater. Despite these large numbers and availability of safe and efficacious vaccines, only 38,000 cases annually are prevented—a meager 8% or less than a 2% reduction in cases, depending on whether nonbacteremic pneumonia is included in the calculations. Although vaccination has had great success in some affluent countries, the current level of activity has had a very small impact globally. The use of conjugates, preferably with a reduced number of doses and in combination with other vaccines or perhaps in fractional doses, should be extended to less privileged countries, where most Hib disease occurs.
Risk and Management of Blood-Borne Infections in Health Care Workers
Authors: Beltrami Elise M. , Williams Ian T. , Shapiro Craig N. , Chamberland Mary E. 
Published: October 2018

SUMMARY
Exposure to blood-borne pathogens poses a serious risk to health care workers (HCWs). We review the risk and management of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in HCWs and also discuss current methods for preventing exposures and recommendations for postexposure prophylaxis. In the health care setting, blood-borne pathogen transmission occurs predominantly by percutaneous or mucosal exposure of workers to the blood or body fluids of infected patients. Prospective studies of HCWs have estimated that the average risk for HIV transmission after a percutaneous exposure is approximately 0.3%, the risk of HBV transmission is 6 to 30%, and the risk of HCV transmission is approximately 1.8%. To minimize the risk of blood-borne pathogen transmission from HCWs to patients, all HCWs should adhere to standard precautions, including the appropriate use of hand washing, protective barriers, and care in the use and disposal of needles and other sharp instruments. Employers should have in place a system that includes written protocols for prompt reporting, evaluation, counseling, treatment, and follow-up of occupational exposures that may place a worker at risk of blood-borne pathogen infection. A sustained commitment to the occupational health of all HCWs will ensure maximum protection for HCWs and patients and the availability of optimal medical care for all who need it.
Bartonella Infection in Animals: Carriership, Reservoir Potential, Pathogenicity, and Zoonotic Potential for Human Infection
Authors: Breitschwerdt Edward B. , Kordick Dorsey L. 
Published: October 2018

SUMMARYRecent observations have begun to support a role for Bartonella spp. as animal as well as human pathogens. Bartonella spp. are vector-transmitted, blood-borne, intracellular, gram-negative bacteria that can induce prolonged infection in the host. Persistent infections in domestic and wild animals result in a substantial reservoir of Bartonella organisms in nature that can serve as a source for inadvertent human infection. The prevalence of bacteremia can range from 50 to 95% in selected rodent, cat, deer, and cattle populations. Dogs infected with Bartonella spp. can develop lameness, endocarditis, granulomatous lymphadenitis, and peliosis hepatis, lesions that have also been reported in association with human infection. Understanding the role of Bartonella spp. as pathogens in cats and other wild or domestic animals awaits the results of additional studies. Considering the extensive animal reservoirs and the large number of insects that have been implicated in the transmission of Bartonella spp., both animal and human exposure to these organisms may be more substantial than is currently believed.
Polysaccharide Immunomodulators as Therapeutic Agents: Structural Aspects and Biologic Function
Authors: Tzianabos Arthur O. 
Published: October 2018

SUMMARYPolysaccharide immunomodulators were first discovered over 40 years ago. Although very few have been rigorously studied, recent reports have revealed the mechanism of action and structure-function attributes of some of these molecules. Certain polysaccharide immunomodulators have been identified that have profound effects in the regulation of immune responses during the progression of infectious diseases, and studies have begun to define structural aspects of these molecules that govern their function and interaction with cells of the host immune system. These polymers can influence innate and cell-mediated immunity through interactions with T cells, monocytes, macrophages, and polymorphonuclear lymphocytes. The ability to modulate the immune response in an appropriate way can enhance the host's immune response to certain infections. In addition, this strategy can be utilized to augment current treatment regimens such as antimicrobial therapy that are becoming less efficacious with the advent of antibiotic resistance. This review focuses on recent studies that illustrate the structural and biologic activities of specific polysaccharide immunomodulators and outlines their potential for clinical use.
Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies?
Authors: Verity Christopher , Winstone Anne Marie , Will Robert , Powell Alison , Baxter Peter , de Sousa Carlos , Gissen Paul , Kurian Manju , Livingston John , McFarland Robert , Pal Suvankar , Pike Michael , Robinson Richard , Wassmer Evangeline , Zuberi Sameer 
Published: October 2018

Objectives
To report investigations performed in children with progressive neurodegenerative diseases reported to this UK study.

Design
Since 1997 paediatric surveillance for variant Creutzfeldt-Jakob disease (vCJD) has been performed by identifying children aged less than 16 years with progressive intellectual and neurological deterioration (PIND) and searching for vCJD among them.

Setting
The PIND Study obtains case details from paediatricians who notify via the British Paediatric Surveillance Unit.

Participants
Between May 1997 and October 2017, a total of 2050 cases meeting PIND criteria had been notified and investigated.

Results
Six children had vCJD. 1819 children had other diagnoses, made in 12 cases by antemortem brain biopsy and in 15 by postmortem investigations. 225 children were undiagnosed: only 3 had antemortem brain biopsies and only 14 of the 108 who died were known to have had autopsies; postmortem neuropathological studies were carried out in just 10% (11/108) and only two had prion protein staining of brain tissue. Of the undiagnosed cases 43% were known to come from Asian British families.

Conclusions
Most of the notified children had a diagnosis other than vCJD to explain their neurological deterioration. None of the undiagnosed cases had the clinical phenotype of vCJD but brain tissue was rarely studied to exclude vCJD. Clinical surveillance via the PIND Study remains the only practical means of searching for vCJD in UK children.
Immunosuppressants and/or antivascular endothelial growth factor inhibitors in punctate inner choroidopathy? Follow-up results with optical coherence tomography angiography
Authors: Pohlmann Dominika , Pleyer Uwe , Joussen Antonia M , Winterhalter Sibylle 
Published: October 2018

PurposeTo report the effectiveness of treatment with antivascular endothelial growth factor (VEGF)-inhibitor and/or immunosuppressants in punctate inner choroidopathy (PIC) using standard imaging modalities and optical coherence tomography angiography (OCTA) over a time period of 16 months.MethodsIn this prospective, unmasked, single-centre study, 23 individuals with PIC underwent imaging with spectral domain OCT, fluorescein angiography, indocyanine green angiography and OCTA. Two groups were formed based on systemic treatment. In case of choroidal neovascularisation (CNV) activity, intravitreal anti-VEGF injections were carried out in both groups.ResultsGroup I included 12 patients (24 eyes) with 18 affected eyes (75%) who did not receive any systemic therapy at baseline. Group II contained 11 patients (22 eyes) who started systemic immunosuppressive therapy on average 2 years before baseline. All eyes with recurrence of CNV or residual fluid (group I: seven eyes; group II: six eyes) received anti-VEGF agents. Group I showed a significant reduction of CNV size (p=0.0078), as well as a decrease of fluid retention (p=0.0078) on OCTA after anti-VEGF injection. Group II did not demonstrate any significant reduction of CNV size, vessel shape or fluid retention post injection. But overall, fluid accumulation was significantly lower in group II (median=0.03 mm2) than in group I (median=0.32 mm2) (p=0.0028).ConclusionImmunosuppressants in addition to anti-VEGF agents showed a significant reduction of fluid accumulation, that is, reduced disease activity. We conclude that there is a benefit and effectiveness of immunosuppressants to control inflammatory secondary CNV in PIC.
Glucose responses to acute and chronic exercise during pregnancy: a systematic review and meta-analysis
Authors: Davenport Margie H , Sobierajski Frances , Mottola Michelle F , Skow Rachel J , Meah Victoria L , Poitras Veronica J , Gray Casey E , Jaramillo Garcia Alejandra , Barrowman Nick , Riske Laurel , James Marina , Nagpal Taniya S , Marchand Andree-Anne , Slater Linda G , Adamo Kristi B , Davies Gregory A , Barakat Ruben , Ruchat Stephanie-May 
Published: October 2018

ObjectiveTo perform a systematic review and meta-analysis to explore the relationship between prenatal exercise and glycaemic control.DesignSystematic review with random-effects meta-analysis and meta-regression.Data sourcesOnline databases were searched up to 6 January 2017.Study eligibility criteriaStudies of all designs were included (except case studies and reviews) if they were published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of acute or chronic exercise, alone (‘exercise-only’) or in combination with other intervention components (eg, dietary; ‘exercise+cointervention’) at any stage of pregnancy), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (glycaemic control).ResultsA total of 58 studies (n=8699) were included. There was ‘very low’ quality evidence showing that an acute bout of exercise was associated with a decrease in maternal blood glucose from before to during exercise (6 studies, n=123; mean difference (MD) −0.94 mmol/L, 95% CI −1.18 to −0.70, I2=41%) and following exercise (n=333; MD −0.57 mmol/L, 95% CI −0.72 to −0.41, I2=72%). Subgroup analysis showed that there were larger decreases in blood glucose following acute exercise in women with diabetes (n=26; MD −1.42, 95% CI −1.69 to −1.16, I2=8%) compared with those without diabetes (n=285; MD −0.46, 95% CI −0.60 to −0.32, I2=62%). Finally, chronic exercise-only interventions reduced fasting blood glucose compared with no exercise postintervention in women with diabetes (2 studies, n=70; MD −2.76, 95% CI −3.18 to −2.34, I2=52%; ‘low’ quality of evidence), but not in those without diabetes (9 studies, n=2174; MD −0.05, 95% CI −0.16 to 0.05, I2=79%).ConclusionAcute and chronic prenatal exercise reduced maternal circulating blood glucose concentrations, with a larger effect in women with diabetes.
US-based cross-sectional survey of clinicians’ knowledge and attitudes about shared decision-making across healthcare professions and specialties
Authors: Forcino Rachel C , Yen Renata West , Aboumrad Maya , Barr Paul J , Schubbe Danielle , Elwyn Glyn , Durand Marie-Anne 
Published: October 2018

ObjectiveIn this study, we aim to compare shared decision-making (SDM) knowledge and attitudes between US-based physician assistants (PAs), nurse practitioners (NPs) and physicians across surgical and family medicine specialties.SettingWe administered a cross-sectional, web-based survey between 20 September 2017 and 1 November 2017.Participants272 US-based NPs, PA and physicians completed the survey. 250 physicians were sent a generic email invitation to participate, of whom 100 completed the survey. 3300 NPs and PAs were invited, among whom 172 completed the survey. Individuals who met the following exclusion criteria were excluded from participation: (1) lack of English proficiency; (2) area of practice other than family medicine or surgery; (3) licensure other than physician, PA or NP; (4) practicing in a country other than the US.ResultsWe found few substantial differences in SDM knowledge and attitudes across clinician types, revealing positive attitudes across the sample paired with low to moderate knowledge. Family medicine professionals (PAs) were most knowledgeable on several items. Very few respondents (3%; 95% CI 1.5% to 6.2%) favoured a paternalistic approach to decision-making.ConclusionsRecent policy-level promotion of SDM may have influenced positive clinician attitudes towards SDM. Positive attitudes despite limited knowledge warrant SDM training across occupations and specialties, while encouraging all clinicians to promote SDM. Given positive attitudes and similar knowledge across clinician types, we recommend that SDM is not confined to the patient-physician dyad but instead advocated among other health professionals.