LEUKOCYTES IN “VIRUS X” INFECTION

Study of blood taken from patients with the recent “Virus X” “flu” syndrome showed slight leukopenia and the presence of abnormal lymphocytes, the most characteristic of which were those showing basophilic cytoplasm. These cells, often called Turk cells, and which the authors have termed “toxic” lymphocytes, are similar to those found in other virus infections.     

Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review

The aim of this review was to assess recent progress in targeted radionuclide tumor therapy, focusing on the best delivery strategies. A literature search was conducted in PubMed, Web of Science, and Scopus using the terms “radionuclides”, “liposomes”, “avidin–biotin interaction”, “theranostic”, and “molecular docking”. The 10 year filter was applied, except for the avidin–biotin interaction. Data were retrieved from both preclinical and clinical settings. Three targeting strategies were considered: pretargeting, liposomes, and ligands. Pretargeting can be achieved by exploiting the avidin–biotin interaction. This strategy seems very promising, although it has been investigated mainly in resectable tumors. Radiolabeled liposomes have attracted new interest as probes to identify the most suitable patients for treatment with liposomal formulations of common chemotherapeutics. The use of ligands for the delivery of radiotherapeutics to a specific target is still the most appealing strategy for treating tumors. The most appropriate ligand can be identified by virtually simulating its interaction with the receptor. All strategies showed great potential for use in targeted radionuclide therapy, but they also have numerous drawbacks. The most promising option is probably the one based on the use of new ligands.     

Problems Related to the Use of Food Additives in the United States

Major problems encountered by enforcement agencies and by regulated industries, respectively, in implementing and conforming to recent food additive laws are reviewed. Decisions as to which substances fall within the broad terms of the legal definition, and which escape by virtue of “generally recognized as safe” (GRAS) status, are often difficult and complex. Distinctions cannot be made solely on the basis of whether substances are old or new, natural or synthetic. Registration of pesticides on a “no residue” basis and establishment of “zero tolerances” for food additives have created an anomalous situation as a result of improvements in sensitivity of analytical techniques which revealed the presence of minute amounts of substances where none were believed to exist. A solution has been recommended by a specially appointed committee of the National Academy of Sciences-National Research Council (U.S.A.). Enforcement of the new food additive laws warrants revision of present labelling requirements to provide for designating chemical ingredients by functional categories rather than by confusing chemical terminology.     

Postviral fatigue syndrome: time for a new approach

Controversial views on the postviral fatigue syndrome (“myalgic encephalomyelitis”) were critically appraised in their historical context and recent advances in research (virology, immunology, neurophysiology, histopathology, and epidemiology) reviewed. Flaws detected in certain aspects of recent research included in particular failure to define fatigue, inadequate assessment of psychological features, and absent or inappropriate control groups. The findings suggest that the fruitless dichotomy of “organic versus functional” should be replaced by a multifactorial approach. Most important, epidemiological studies with explicit operational case definition are essential before progress can be made in the management of this distressing disorder.     

HUMAN PSITTACOSIS CURED BY PENICILLIN THERAPY

A number of recent reports in the literature have told of cure of psittacosis in man following enormous doses of penicillin in the early stages of the disease. In most of these cases, however, the infection was experimentally induced in laboratory studies. Given late and in inadequate amounts, penicillin apparently has no beneficial effect.With a means of treatment at hand, and effective if started early, careful analysis of all cases of “atypical pneumonia” is indicated with a view to determining if the infecting agent might not be the psittacosis virus. A history of contact with birds or bird droppings should be sought in all cases of “atypical pneumonia.”A case is reported in which the patient, because of contact with birds, was suspected early of having psittacosis. No benefit was noted following therapy with 100,000 units of penicillin every three hours for one day, but rapid recovery ensued when the dose was doubled.     

A Re-Examination of the History of Etiologic Confusion between Dengue and Chikungunya

Contrary to the perception of many researchers that the recent invasion of chikungunya (CHIK) in the Western Hemisphere marked the first episode in history, a recent publication reminded them that CHIK had prevailed in the West Indies and southern regions of the United States from 1827–1828 under the guise of “dengue” (DEN), and that many old outbreaks of so-called “dengue” actually represented the CHIK cases erroneously identified as “dengue.” In hindsight, this confusion was unavoidable, given that the syndromes of the two diseases—transmitted by the same mosquito vector in urban areas—are very similar, and that specific laboratory-based diagnostic techniques for these diseases did not exist prior to 1940. While past reviewers reclassified problematic “dengue” outbreaks as CHIK, primarily based on manifestation of arthralgia as a marker of CHIK, they neither identified the root cause of the alleged misdiagnosis nor did they elaborate on the negative consequences derived from it. This article presents a reconstructed history of the genesis of the clinical definition of dengue by emphasizing problems with the definition, subsequent confusion with CHIK, and the ways in which physicians dealt with the variation in dengue-like (“dengue”) syndromes. Then, the article identifies in those records several factors complicating reclassification, based on current practice and standards. These factors include terms used for characterizing joint problems, style of documenting outbreak data, frequency of manifestation of arthralgia, possible involvement of more than one agent, and occurrence of the principal vector. The analysis of those factors reveals that while some of the old “dengue” outbreaks, including the 1827–1828 outbreaks in the Americas, are compatible with CHIK, similar reclassification of other “dengue” outbreaks to CHIK is difficult because of a combination of the absence of pathognomonic syndrome in these diseases and conflicting background information.     

A new genus for a rare African vespertilionid bat: insights from South Sudan

A new genus is proposed for the strikingly patterned African vespertilionid “Glauconycteris” superba Hayman, 1939 on the basis of cranial and external morphological comparisons. A review of the attributes of a newly collected specimen from South Sudan (a new country record) and other museum specimens of “Glauconycteris” superba suggests that “Glauconycteris” superba is markedly distinct ecomorphologically from other species classified in Glauconycteris and is likely the sister taxon to Glauconycteris sensu stricto. The recent capture of this rarely collected but widespread bat highlights the need for continued research in tropical sub-Saharan Africa and in particular, for more work in western South Sudan, which has received very little scientific attention. New country records for Glauconycteris cf. poensis (South Sudan) and Glauconycteris curryae (Gabon) are also reported.     

An expression system for Gustatory receptors—and why it failed

A recent paper by the Dahankuar laboratory suggested that single Drosophila sugar receptors proteins accurately mediate sugar detection when ectopically expressed in olfactory neurons of the antenna. These findings contra-dict numerous previously published electrophysiological and behavioral investigations, which all point towards heteromultimeric sugar taste receptors. Here, I provide some explanation why this “pseudo-heterologous” expression system may have led to this misleading conclusion.     

From imaging to understanding: Frontiers in Live Cell Imaging, Bethesda, MD, April 19-21, 2006

A recent meeting entitled Frontiers in Live Cell Imaging was attended by more than 400 cell biologists, physicists, chemists, mathematicians, and engineers. Unlike typical special topics meetings, which bring together investigators in a defined field primarily to review recent progress, the purpose of this meeting was to promote cross-disciplinary interactions by introducing emerging methods on the one hand and important biological applications on the other. The goal was to turn live cell imaging from a “technique” used in cell biology into a new exploratory science that combines a number of research fields.     

The “Naked Coral” Hypothesis Revisited – Evidence for and Against Scleractinian Monophyly

The relationship between Scleractinia and Corallimorpharia, Orders within Anthozoa distinguished by the presence of an aragonite skeleton in the former, is controversial. Although classically considered distinct groups, some phylogenetic analyses have placed the Corallimorpharia within a larger Scleractinia/Corallimorpharia clade, leading to the suggestion that the Corallimorpharia are “naked corals” that arose via skeleton loss during the Cretaceous from a Scleractinian ancestor. Scleractinian paraphyly is, however, contradicted by a number of recent phylogenetic studies based on mt nucleotide (nt) sequence data. Whereas the “naked coral” hypothesis was based on analysis of the sequences of proteins encoded by a relatively small number of mt genomes, here a much-expanded dataset was used to reinvestigate hexacorallian phylogeny. The initial observation was that, whereas analyses based on nt data support scleractinian monophyly, those based on amino acid (aa) data support the “naked coral” hypothesis, irrespective of the method and with very strong support. To better understand the bases of these contrasting results, the effects of systematic errors were examined. Compared to other hexacorallians, the mt genomes of “Robust” corals have a higher (A+T) content, codon usage is far more constrained, and the proteins that they encode have a markedly higher phenylalanine content, leading us to suggest that mt DNA repair may be impaired in this lineage. Thus the “naked coral” topology could be caused by high levels of saturation in these mitochondrial sequences, long-branch effects or model violations. The equivocal results of these extensive analyses highlight the fundamental problems of basing coral phylogeny on mitochondrial sequence data.     

Distributional records of Ross Sea (Antarctica) Tanaidacea from museum samples stored in the collections of the Italian National Antarctic Museum (MNA) and the New Zealand National Institute of Water and Atmospheric Research (NIWA)

Here we present distributional records for Tanaidacea specimens collected during several Antarctic expeditions to the Ross Sea: the Italian PNRA expeditions (“V”, 1989/1990; “XI”, 1995/1996; “XIV”, 1998/1999; “XIX”, 2003/2004; “XXV”, 2009/2010) and the New Zealand historical (New Zealand Oceanographic Institute, NZOI, 1958-1961) and recent (“TAN0402 BIOROSS” voyage, 2004 and “TAN0802 IPY-CAML Oceans Survey 20/20” voyage, 2008) expeditions. Tanaidaceans were obtained from bottom samples collected at depths ranging from 16 to 3543 m by using a variety of sampling gears. On the whole, this contribution reports distributional data for a total of 2953 individuals belonging to 33 genera and 50 species. All vouchers are permanently stored in the Italian National Antarctic Museum collection (MNA), Section of Genoa (Italy) and at the National Institute of Water and Atmospheric Research (NIWA Invertebrate Collection), Wellington (New Zealand).     

Young Children Understand the Normative Implications of Future-Directed Speech Acts

Much recent research has shown that the capacity for mental time travel and temporal reasoning emerges during the preschool years. Nothing is known so far, however, about young children''s grasp of the normative dimension of future-directed thought and speech. The present study is the first to show that children from age 4 understand the normative outreach of such future-directed speech acts: subjects at time 1 witnessed a speaker make future-directed speech acts about/towards an actor A, either in imperative mode (“A, do X!”) or as a prediction (“the actor A will do X”). When at time 2 the actor A performed an action that did not match the content of the speech act at time 1, children identified the speaker as the source of a mistake in the prediction case, and the actor as the source of the mistake in the imperative case and leveled criticism accordingly. These findings add to our knowledge about the emergence and development of temporal cognition in revealing an early sensitivity to the normative aspects of future-orientation.     

Enhancements to the Rosetta Energy Function Enable Improved Identification of Small Molecules that Inhibit Protein-Protein Interactions

Protein-protein interactions are among today’s most exciting and promising targets for therapeutic intervention. To date, identifying small-molecules that selectively disrupt these interactions has proven particularly challenging for virtual screening tools, since these have typically been optimized to perform well on more “traditional” drug discovery targets. Here, we test the performance of the Rosetta energy function for identifying compounds that inhibit protein interactions, when these active compounds have been hidden amongst pools of “decoys.” Through this virtual screening benchmark, we gauge the effect of two recent enhancements to the functional form of the Rosetta energy function: the new “Talaris” update and the “pwSHO” solvation model. Finally, we conclude by developing and validating a new weight set that maximizes Rosetta’s ability to pick out the active compounds in this test set. Looking collectively over the course of these enhancements, we find a marked improvement in Rosetta’s ability to identify small-molecule inhibitors of protein-protein interactions.     

From “Silent Teachers” to Models

For decades, embalmed cadavers have played an important role in teaching anatomy to the scientists and doctors of the future. Most anatomy departments use a traditional formaldehyde-based embalming method, but formalin embalming makes the bodies very rigid, which limits their usefulness for procedures other than dissection. A more recent embalming method developed by W. Thiel has allowed these “silent teachers” to take on a further role in applied anatomy research and teaching: to act as models for surgical training and medical research.     

Call Off the Dog(ma): M1/M2 Polarization Is Concurrent following Traumatic Brain Injury

Following the primary mechanical impact, traumatic brain injury (TBI) induces the simultaneous production of a variety of pro- and anti-inflammatory molecular mediators. Given the variety of cell types and their requisite expression of cognate receptors this creates a highly complex inflammatory milieu. Increasingly in neurotrauma research there has been an effort to define injury-induced inflammatory responses within the context of in vitro defined macrophage polarization phenotypes, known as “M1” and “M2”. Herein, we expand upon our previous work in a rodent model of TBI to show that the categorization of inflammatory response cannot be so easily delineated using this nomenclature. Specifically, we show that TBI elicited a wide spectrum of concurrent expression responses within both pro- and anti-inflammatory arms. Moreover, we show that the cells principally responsible for the production of these inflammatory mediators, microglia/macrophages, simultaneously express both “M1” and “M2” phenotypic markers. Overall, these data align with recent reports suggesting that microglia/macrophages cannot adequately switch to a polarized “M1-only” or “M2-only” phenotype, but display a mixed phenotype due to the complex signaling events surrounding them.     

USE OF THE ARTIFICIAL KIDNEY—Its Place in the Treatment of Acute Renal Failure

Of 57 patients with severe, but potentially reversible, acute renal failure who were observed during a recent four-year period, some had dialysis with an artificial kidney and some did not.Twenty survived with the standard “conservative” management alone; 19 survived with a combination of “conservative” and “intensive” (that is, artificial kidney) treatment; 18 patients died.One error that was made in the management of all 18 patients who died, was excessive delay in the use of the artificial kidney.Hemodialysis should be used whenever serious electrolyte abnormality exists, whenever the blood urea nitrogen exceeds 150 mg. per 100 cc. or whenever clinical signs of uremia first appear. One or more of these indications will usually, but not always, become evident between the fifth and the eighth day of virtual anuria.     

The A.M.A. Meeting,June 25-30, 1961, New York City

This “news and comment” report on the recent annual meeting of the American Medical Association was written by Mr. Ed Clancy, director of public relations of the California Medical Association.     

IS IT NEUROSIS?

So-called “minor psychiatry,” the treatment of neurosis in persons who are not psychotic, may well be undertaken by the general practitioner.The first duty of the physician in dealing with a neurotic person is to determine whether psychosis may develop. He must be patient and thorough in hearing the history of the case and should have full information on the patient''s life and family.A recent classification of the neuroses is given and the more generally recognized symptoms of these conditions are described.     

The Novel New Jersey Eyewitness Instruction Induces Skepticism but Not Sensitivity

In recent decades, social scientists have shown that the reliability of eyewitness identifications is much worse than laypersons tend to believe. Although courts have only recently begun to react to this evidence, the New Jersey judiciary has reformed its jury instructions to notify jurors about the frailties of human memory, the potential for lineup administrators to nudge witnesses towards suspects that they police have already identified, and the advantages of alternative lineup procedures, including blinding of the administrator. This experiment tested the efficacy of New Jersey’s jury instruction. In a 2×2 between-subjects design, mock jurors (N = 335) watched a 35-minute murder trial, wherein identification quality was either “weak” or “strong” and either the New Jersey or a “standard” instruction was delivered. Jurors were more than twice as likely to convict when the standard instruction was used (OR = 2.55; 95% CI = 1.37–4.89, p < 0.001). The New Jersey instruction, however, did not improve juror''s ability to discern quality; rather, jurors receiving those instructions indiscriminatingly discounted “weak” and “strong” testimony in equal measure.