Measurement of Side Effects of Drugs

In a clinical trial of two antirheumatic agents two methods of collection of side effects were used, one with and the other without a check list of possible symptoms. Findings suggested that the use of a check list interfered with the collection of side effects. Known side effects of aspirin—tinnitus, deafness, and gastrointestinal disturbance—were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used.     

Decreased Prevalence of Lymphatic Filariasis among Diabetic Subjects Associated with a Diminished Pro-Inflammatory Cytokine Response (CURES 83)

Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF) and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416) as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%]) compared to pre-diabetic subjects [9.1%] (p = 0.0095) and non-diabetic subjects [10.4%] (p = 0.0463). A significant decrease in filarial antigen load (p = 0.04) was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines—IL-6 and GM-CSF—were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines—IL-10, IL-13 and TGF-β—between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF.     

Orudis in Management of Rheumatoid Arthritis and Osteoarthrosis of the Hip: Comparison with Indomethacin

In double-blind cross-over studies in 46 patients with rheumatoid arthritis and in 42 patients with osteoarthrosis of the hip, Orudis—a new non-steroidal anti-inflammatory agent—has been shown to be well tolerated and to have comparable therapeutic efficacy with indomethacin when given in equal dosage. Side effects were less severe with Orudis. The results suggest that Orudis will prove valuable in the clinical management of rheumatic diseases.     

Clinical Trial of Mefruside,a New Diuretic

A controlled clinical trial of a new diuretic—mefruside—is reported, in which it was compared with frusemide in 15 normal subjects and 15 patients with fluid retention. It was found to be an effective diuretic which, in the patients, produced a significantly greater excretion of water and electrolytes than an equal dose of frusemide. Its smooth prolonged action, maximal in the first 12 hours, made it of particular value for maintenance therapy. In a short-term trial on a further 15 hypertensive patients mefruside was shown to have a useful hypotensive action. The drug was well tolerated with minimal side effects.     

Recollection-Based Retrieval Is Influenced by Contextual Variation at Encoding but Not at Retrieval

In this article, we investigated the effects of variations at encoding and retrieval on recollection. We argue that recollection is more likely to be affected by the processing that information undergoes at encoding than at retrieval. To date, manipulations shown to affect recollection were typically carried out at encoding. Therefore, an open question is whether these same manipulations would also affect recollection when carried out at retrieval, or whether there is an inherent connection between their effects on recollection and the encoding stage. We therefore manipulated, at either encoding or retrieval, fluency of processing (Experiment 1)—typically found not to affect recollection—and the amount of attentional resources available for processing (Experiments 2 and 3)—typically reported to affect recollection. We found that regardless of the type of manipulation, recollection was affected more by manipulations carried out at encoding and was essentially unaffected when these manipulations were carried out at retrieval. These findings suggest an inherent dependency between recollection-based retrieval and the encoding stage. It seems that because recollection is a contextual-based retrieval process, it is determined by the processing information undergoes at encoding—at the time when context is bound with the items—but not at retrieval—when context is only recovered.     

Double-blind Cross-over Trial of Flurbiprofen and Phenylbutazone in Ankylosing Spondylitis

A double-blind cross-over study in 35 patients with ankylosing spondylitis was carried out comparing flurbiprofen (150 mg daily)—a new non-steroidal anti-inflammatory agent—with phenylbutazone (300 mg daily) over a four-week period. Flurbiprofen was well tolerated and shown to have therapeutic efficacy approaching that of phenylbutazone. The results suggest that flurbiprofen may prove a valuable alternative in the treatment of ankylosing spondylitis, and longterm efficacy and tolerance studies are clearly indicated.     

Use of a Novel Fluorinated Organosulfur Compound To Isolate Bacteria Capable of Carbon-Sulfur Bond Cleavage

The vacuum residue fraction of heavy crudes contributes to the viscosity of these oils. Specific microbial cleavage of C—S bonds in alkylsulfide bridges that form linkages in this fraction may result in dramatic viscosity reduction. To date, no bacterial strains have been shown conclusively to cleave C—S bonds within alkyl chains. Screening for microbes that can perform this activity was greatly facilitated by the use of a newly synthesized compound, bis-(3-pentafluorophenylpropyl)-sulfide (PFPS), as a novel sulfur source. The terminal pentafluorinated aromatic rings of PFPS preclude growth of aromatic ring-degrading bacteria but allow for selective enrichment of strains capable of cleaving C—S bonds. A unique bacterial strain, Rhodococcus sp. strain JVH1, that used PFPS as a sole sulfur source was isolated from an oil-contaminated environment. Gas chromatography-mass spectrometry analysis revealed that JVH1 oxidized PFPS to a sulfoxide and then a sulfone prior to cleaving the C—S bond to form an alcohol and, presumably, a sulfinate from which sulfur could be extracted for growth. Four known dibenzothiophene-desulfurizing strains, including Rhodococcus sp. strain IGTS8, were all unable to cleave the C—S bond in PFPS but could oxidize PFPS to the sulfone via the sulfoxide. Conversely, JVH1 was unable to oxidize dibenzothiophene but was able to use a variety of alkyl sulfides, in addition to PFPS, as sole sulfur sources. Overall, PFPS is an excellent tool for isolating bacteria capable of cleaving subterminal C—S bonds within alkyl chains. The type of desulfurization displayed by JVH1 differs significantly from previously described reaction results.     

Pigeons (Columba livia) as Trainable Observers of Pathology and Radiology Breast Cancer Images

Pathologists and radiologists spend years acquiring and refining their medically essential visual skills, so it is of considerable interest to understand how this process actually unfolds and what image features and properties are critical for accurate diagnostic performance. Key insights into human behavioral tasks can often be obtained by using appropriate animal models. We report here that pigeons (Columba livia)—which share many visual system properties with humans—can serve as promising surrogate observers of medical images, a capability not previously documented. The birds proved to have a remarkable ability to distinguish benign from malignant human breast histopathology after training with differential food reinforcement; even more importantly, the pigeons were able to generalize what they had learned when confronted with novel image sets. The birds’ histological accuracy, like that of humans, was modestly affected by the presence or absence of color as well as by degrees of image compression, but these impacts could be ameliorated with further training. Turning to radiology, the birds proved to be similarly capable of detecting cancer-relevant microcalcifications on mammogram images. However, when given a different (and for humans quite difficult) task—namely, classification of suspicious mammographic densities (masses)—the pigeons proved to be capable only of image memorization and were unable to successfully generalize when shown novel examples. The birds’ successes and difficulties suggest that pigeons are well-suited to help us better understand human medical image perception, and may also prove useful in performance assessment and development of medical imaging hardware, image processing, and image analysis tools.     

Comparative studies of three methods for measuring pepsin activity

Comparison has been made of a simple method originated by Absolon and modified in our laboratories for assay of proteolytic activity using RISA (radioactive iodinated serum albumin—Abbott Laboratories), with the commonly used photometric methods of Anson and Kunitz. In this method, pepsin was incubated with an albumin substrate containing RISA, followed by precipitation of the undigested substrate with trichloroacetic acid and measurement of radioactive digestion products in the supernatant fluid. The I¹³¹—albumin bond was shown in the present studies to be altered only by the proteolytic activity, and not by the incubation procedures at various values of pH. Any free iodine present originally in the RISA was removed by a single passage through a resin column (amberlite IRA-400-C1). Pepsin was shown to be most stable in solution at a pH of 5.5. Activity of pepsin was shown to be maximal when it was incubated with albumin at a pH of 2.5. Pepsin activity was shown to be altered in the presence of various electrolytes. Pepsin activity measured by the RISA and Anson methods as a function of concentration or of time of incubation indicated that these two methods are in good agreement and are equally sensitive. Consistently smaller standard errors were obtained by the RISA method of pepsin assay than were obtained with either of the other methods.     

Protein restriction and branched‐chain amino acid restriction promote geroprotective shifts in metabolism

The proportion of humans suffering from age‐related diseases is increasing around the world, and creative solutions are needed to promote healthy longevity. Recent work has clearly shown that a calorie is not just a calorie—and that low protein diets are associated with reduced mortality in humans and promote metabolic health and extended lifespan in rodents. Many of the benefits of protein restriction on metabolism and aging are the result of decreased consumption of the three branched‐chain amino acids (BCAAs), leucine, isoleucine, and valine. Here, we discuss the emerging evidence that BCAAs are critical modulators of healthy metabolism and longevity in rodents and humans, as well as the physiological and molecular mechanisms that may drive the benefits of BCAA restriction. Our results illustrate that protein quality—the specific composition of dietary protein—may be a previously unappreciated driver of metabolic dysfunction and that reducing dietary BCAAs may be a promising new approach to delay and prevent diseases of aging.     

Emotional Dynamics in the Age of Misinformation

According to the World Economic Forum, the diffusion of unsubstantiated rumors on online social media is one of the main threats for our society. The disintermediated paradigm of content production and consumption on online social media might foster the formation of homogeneous communities (echo-chambers) around specific worldviews. Such a scenario has been shown to be a vivid environment for the diffusion of false claim. Not rarely, viral phenomena trigger naive (and funny) social responses—e.g., the recent case of Jade Helm 15 where a simple military exercise turned out to be perceived as the beginning of the civil war in the US. In this work, we address the emotional dynamics of collective debates around distinct kinds of information—i.e., science and conspiracy news—and inside and across their respective polarized communities. We find that for both kinds of content the longer the discussion the more the negativity of the sentiment. We show that comments on conspiracy posts tend to be more negative than on science posts. However, the more the engagement of users, the more they tend to negative commenting (both on science and conspiracy). Finally, zooming in at the interaction among polarized communities, we find a general negative pattern. As the number of comments increases—i.e., the discussion becomes longer—the sentiment of the post is more and more negative.     

Selective Influences of Precision and Power Grips on Speech Categorization

Recent studies have shown that articulatory gestures are systematically associated with specific manual grip actions. Here we show that executing such actions can influence performance on a speech-categorization task. Participants watched and/or listened to speech stimuli while executing either a power or a precision grip. Grip performance influenced the syllable categorization by increasing the proportion of responses of the syllable congruent with the executed grip (power grip—[ke] and precision grip—[te]). Two follow-up experiments indicated that the effect was based on action-induced bias in selecting the syllable.     

The isolation of wheat germ nuclei and some aspects of their glycolytic metabolism

1. A procedure for isolating nuclei of the wheat germ in non-aqueous media has been described. 2. Such nuclei were shown to constitute about 50 per cent of the protoplasmic mass and to have a ribonucleic acid content of an order equivalent to that of the cytoplasm. 3. Studies of the distribution of the enzymes—aldolase, phosphoglyceraldehyde dehydrogenase, enolase, and pyruvate kinase—have revealed that the nuclei are the most vigorous sites of glycolytic activity. 4. Analysis of the DPN content of the nuclei in calf tissues—liver, pancreas, and heart—pointed to the probability that glycolytic activity is a characteristic common to many nuclei. 5. The significance of glycolytic activity to nuclear function has been discussed and some suggestive comparisons made between the two energy-yielding systems of glycolytic and oxidative phosphorylation.     

Methyl jasmonate and transpiration in barley

Transpirational water loss from barley (Hordeum vulgare L. var Morrison) leaves was determined gravimetrically. In contrast to the known effects of other growth regulating compounds, it is shown that methyl jasmonate—used either as an airborne vapor or in the transpiration stream—is not acting as a primary short-term modulator of stomatal behavior in this species.     

Comparison of Birth Weight/Gestation Distribution in Cases of Stillbirth and Neonatal Death According to Lesions Found at Necropsy

The birth weight/gestation distribution of a large series of cases of perinatal death has been analysed according to the lesion (or lesions) present at necropsy. Among the lesions associated with low gestation babies dying with hyaline membranes have a much higher mean birth weight for gestation than either the babies with intraventricular haemorrhage or “no cause found.” Among infants dying of intrapartum asphyxia or cerebral birth trauma it was found that those who were stillborn with trauma had, at term, a significantly higher mean birth weight than the control livebirths, and that, at all gestations, the stillbirths with trauma were, on average, heavier than the babies dying neonatally with this lesion. Cases of intrapartum asphyxia were smaller than the stillbirths with trauma, but those dying during the second stage of labour were larger than those dying during the first stage.Cases of intrauterine pneumonia—that is, stillbirths and first-day deaths—were also shown to be larger for length of gestation than cases of extrauterine pneumonia—that is, deaths between the second and the 28th day. The cases with haemorrhagic pneumonia, however, were, at least at term, smaller than the cases of extrauterine pneumonia, and cases of massive pulmonary haemorrhage showed evidence of growth retardation at all gestations.     

What Would Jaws Do? The Tyranny of Film and the Relationship between Gaze and Higher-Level Narrative Film Comprehension

What is the relationship between film viewers’ eye movements and their film comprehension? Typical Hollywood movies induce strong attentional synchrony—most viewers look at the same things at the same time. Thus, we asked whether film viewers’ eye movements would differ based on their understanding—the mental model hypothesis—or whether any such differences would be overwhelmed by viewers’ attentional synchrony—the tyranny of film hypothesis. To investigate this question, we manipulated the presence/absence of prior film context and measured resulting differences in film comprehension and eye movements. Viewers watched a 12-second James Bond movie clip, ending just as a critical predictive inference should be drawn that Bond’s nemesis, “Jaws,” would fall from the sky onto a circus tent. The No-context condition saw only the 12-second clip, but the Context condition also saw the preceding 2.5 minutes of the movie before seeing the critical 12-second portion. Importantly, the Context condition viewers were more likely to draw the critical inference and were more likely to perceive coherence across the entire 6 shot sequence (as shown by event segmentation), indicating greater comprehension. Viewers’ eye movements showed strong attentional synchrony in both conditions as compared to a chance level baseline, but smaller differences between conditions. Specifically, the Context condition viewers showed slightly, but significantly, greater attentional synchrony and lower cognitive load (as shown by fixation probability) during the critical first circus tent shot. Thus, overall, the results were more consistent with the tyranny of film hypothesis than the mental model hypothesis. These results suggest the need for a theory that encompasses processes from the perception to the comprehension of film.     

Fingerspelling as a Novel Gateway into Reading Fluency in Deaf Bilinguals

Studies have shown that American Sign Language (ASL) fluency has a positive impact on deaf individuals’ English reading, but the cognitive and cross-linguistic mechanisms permitting the mapping of a visual-manual language onto a sound-based language have yet to be elucidated. Fingerspelling, which represents English orthography with 26 distinct hand configurations, is an integral part of ASL and has been suggested to provide deaf bilinguals with important cross-linguistic links between sign language and orthography. Using a hierarchical multiple regression analysis, this study examined the relationship of age of ASL exposure, ASL fluency, and fingerspelling skill on reading fluency in deaf college-age bilinguals. After controlling for ASL fluency, fingerspelling skill significantly predicted reading fluency, revealing for the first-time that fingerspelling, above and beyond ASL skills, contributes to reading fluency in deaf bilinguals. We suggest that both fingerspelling—in the visual-manual modality—and reading—in the visual-orthographic modality—are mutually facilitating because they share common underlying cognitive capacities of word decoding accuracy and automaticity of word recognition. The findings provide support for the hypothesis that the development of English reading proficiency may be facilitated through strengthening of the relationship among fingerspelling, sign language, and orthographic decoding en route to reading mastery, and may also reveal optimal approaches for reading instruction for deaf and hard of hearing children.     

Electron Microscope Observations of the Melanocyte of the Human Epidermis

Using standard osmium fixation and methacrylate embedding techniques, a study has been made of the melanocyte of human biopsy skin removed under general and local anaesthesia. Melanogenesis was easily observable in the melanocytes, but immature pigment granules were rarely seen in the Malpighian cells. The passage of melanin from melanocyte to Malpighian cell—cytocrine secretion—is thought to have been observed. Phagocytes near the dermal-epidermal junction seem to have their pigment granules in vacuoles, rather than surrounded directly by the cytoplasmic matrix as in the melanocytes. This, together with the failure to observe "effete" melanocytes, prompts the suggestion that the phagocytes are melanocytes which have migrated from the epidermis into the dermis. A melanin granule is shown with alternating dark and lighter transverse striations, concerning which structure little can at present be said.     

Molecular characterization of geminivirus-derived small RNAs in different plant species

DNA geminiviruses are thought to be targets of RNA silencing. Here, we characterize small interfering (si) RNAs—the hallmarks of silencing—associated with Cabbage leaf curl begomovirus in Arabidopsis and African cassava mosaic begomovirus in Nicotiana benthamiana and cassava. We detected 21, 22 and 24 nt siRNAs of both polarities, derived from both the coding and the intergenic regions of these geminiviruses. Genetic evidence showed that all the 24 nt and a substantial fraction of the 22 nt viral siRNAs are generated by the dicer-like proteins DCL3 and DCL2, respectively. The viral siRNAs were 5′ end phosphorylated, as shown by phosphatase treatments, and methylated at the 3′-nucleotide, as shown by HEN1 miRNA methylase-dependent resistance to β-elimination. Similar modifications were found in all types of endogenous and transgene-derived siRNAs tested, but not in a major fraction of siRNAs from a cytoplasmic RNA tobamovirus. We conclude that several distinct silencing pathways are involved in DNA virus-plant interactions.     

Peripheral Vasodilators in the Treatment of Macular Degenerative Changes in the Eye

Four peripheral vasodilators — tolazoline HCl (Priscoline), nicotinic acid, nicotinyl alcohol (Roniacol), and nylidrin HCl (Arlidin)—were studied in 203 patients over a 13-year period as treatment for macular degenerative changes in the eye.Visual acuity was improved or maintained in 87%. Excellent results were obtained in the treatment of macular edema following cataract surgery and in older patients with diabetic retinopathy. In 126 out of 145 patients with senile macular degeneration, improvement or stabilization was obtained.For all the types of macular degeneration, nylidrin HCl was the most effective of the drugs studied and had the fewest side effects.A recent report based upon animal experiments advises against the use of peripheral vasodilators in degenerative arterial diseases of the eye; however, the assumption made therein that blood volume is a measure of blood flow cannot be accepted. Peripheral vasodilator therapy, which long-term clinical study has shown to be valuable in the treatment of macular degeneration, should not therefore be denied to these patients.