Acute skin irritant effects of cyanobacteria (blue-green algae) in healthy volunteers

Objective : To assess the skin irritant potential of a range of laboratory grown cyanobacterial species using skin-patch testing on human volunteers.
Methods : Cell suspensions and extracts of cyanobacterial cultures of Microcystis aeruginosa (non-toxic strain), Anabaena circinalis and Nodularia spumigena were applied to 64 volunteers in one trial, and Microcystis aeruginosa (toxic strain), Apanocapsa incerta and Cylindrospermopsis raciborskii were applied to 50 volunteers in a second trial. Six cell concentrations of each organism in the range from less than 5,000 to greater than 200,000 cells/ml were applied in random order using adhesive skin patches (Finn Chambers). In addition, the applications included two treatments of each cyanobacterial species, involving whole and lysed cells, and positive (sodium lauryl sulphate) and negative (culture media) controls. Patches were removed after 24 hours and assessment of erythema was made by a dermatologist blinded to the species, cell type and concentration.
Results : On average, between 20% and 24% of individuals with 95% confidence interval ±8% reacted across the concentration range tested for these cyanobacterial species. The reaction rates were lower (11% to 15%) among the subset of subjects not reacting to negative controls. The reaction was mostly mild, and in all cases was resolved without treatment. This was the case for both whole and lysed cells with little difference in reaction rates between these two treatments. There was also no dose-response across the concentration range for any of the cyanobacterial species tested.
Conclusion : A small proportion of healthy people (around 20%) may develop a skin reaction to cyanobacteria in the course of normal water recreation, but the reaction is mild and resolved without treatment.     

The Basis of Hyperspecificity in Autism: A Preliminary Suggestion Based on Properties of Neural Nets

This article reviews a few key ideas about the representation of information in neural networks and uses these ideas to address one aspect of autism, namely, the apparent hyperspecificity that is often seen in autistic children's application of previously acquired information. Hyperspecificity is seen as reflecting a possible feature of the neural codes used to represent concepts in the autistic brain.     

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.Objective: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.Methods: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.Results: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.Discussion: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343     

Insect management products from Malian traditional medicine--establishing systematic criteria for their identification

In material-resource poor countries like Mali, traditional practices incorporate the use of plants for medicinal purposes. Ethnobotanical research has documented traditional uses of plants, while concomitant studies by natural product chemists, ethnobotanists, and microbiologists have verified the efficacy of using traditional medicinal plants that have proven antimicrobial activity. These plants may also be used to protect agricultural crops pre-harvest and post-harvest from insect herbivory. In Mali, subsistence farmers, regional scientists, and extension specialists rely on local plants for many medicinal needs and are amenable to using traditional plant materials for insect pest management. The goal of this research was to develop Integrated Pest Management (IPM) strategies using Malian traditional medicine as a discovery lead. The discovery premise was based on identifying plants through a matrix approach utilizing agricultural scientists, traditional practitioners, and subsistence farmers. We hypothesized that plants used in traditional medicine with antimicrobial activity lead to potential insect pest management agents. To test our hypothesis, we developed a four-step process for selecting Malian plant species. Seven criteria were selected to create a systematic matrix to identify the most promising plant materials for practical, affordable, ecologically-sound insect management by Malian farmers. In the first step of the process, we developed a list of 294 medicinal Malian plant species which were evaluated using the matrix. Sixty-seven plant species met our main criteria. After the environmental soundness of these species was evaluated using four minor criteria, 50 species emerged from this pre-chemical, pre-bioassay process for further consideration in IPM programs in Mali.     

Is laparoscopically assisted radical vaginal hysterectomy for cervical carcinoma safe? A case control study with follow up

Objective  To compare a new surgical approach, laparoscopically assisted radical vaginal hysterectomy (LARVH) with open radical hysterectomy in women with cervical cancer. Can selected women benefit from the minimally invasive approach without compromising safety (recurrence rate) and morbidity (complications)?
Design  Retrospective case control study.
Setting  A tertiary referral unit for gynaecological malignancies.
Population  Thirty women undergoing LARVH were included and compared with 30 women undergoing open radical surgery. The control group was matched for age, body mass index and disease stage.
Methods  Retrospective collection of data from patient files and follow up.
Main outcome measures  Recurrence rate, complication rate, hospital stay, nodal counts, blood loss, operating time.
Results  Recurrence rates were equal (6.7%). There was one death, in the LARVH group. Follow up was mean 31 months in the LARVH group and 30.9 months in the open group. Blood loss as measured by mean drop in haemoglobin was greater in the open group (2.03 versus 3.01 g/dl, P = 0.02). Transfusions were given in 40% of women in the open group and 16.7% in the LARVH group. Hospital stay was significantly less in the LARVH group (5.9 versus 7.8 nights, P = 0.003). Mean operating time was longer in the LARVH group (131 versus 187 minutes P = 0.0001). Mean nodal counts did not differ significantly (17.4 in open vs 14.8 in LARVH, P > 0.05). There were seven perioperative complications in the open group and four in the LARVH group. There have been two recurrences in each group (6.67%) at mean follow up of 31 (LARVH) and 30.9 (open) months.
Conclusions  The first 30 LARVH procedures performed in this unit are comparable in terms of safety (recurrence rate and complication rate) and economic factors (shorter hospital stay mitigating longer operating time). Further development of this technique is warranted.     

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial

Context  Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. Objective  To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Design and Setting  Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. Patients  Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. Intervention  Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). Main Outcome Measures  Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. Results  Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). Conclusion  Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.      

Cancer morbidity in nitrate fertilizer workers

Summary A cohort of 2,131 male nitrate fertilizer workers was evaluated for cancer morbidity from 1963 to 1986. No significant increase in total cancer, stomach cancer (5 actual vs 6.7 expected cases), or lung cancer (13 vs 13 expected) was found. On the other hand, 26 actual cases of prostate cancer were observed vs 16 expected cases (standardized morbidity ratio, SMR = 161; 95%, confidence interval, CI = 107–239). This risk increase however, was, not enhanced by applying at least a 10-year latency period. In a cohort of 1,148 male fertilizer workers who had never been exposed to nitrate, there was an increased incidence of lung cancer (SMR = 151,95% CI = 103–220) but not of stomach cancer or prostate cancer. There was no association between airborne nitrate exposure dose and total cancer, stomach cancer, lung cancer or prostate cancer, respectively.     

HIV-1 infection alters the retinol-binding protein:transthyretin ratio even in the absence of the acute phase response

The ratio of retinol-binding protein (RBP) to transthyretin (TTR) has been proposed as an indirect method with which to assess vitamin A status in the context of inflammation. Few studies have been conducted among adults, and none examined the effect of HIV-1 infection. Our goal was to assess the RBP:TTR ratio among adults, including the effects of HIV-1 and the acute phase response. We used data from a cross-sectional study of 600 Kenyan women, of whom 400 had HIV-1. The effect of vitamin A supplementation among the HIV-1-infected participants was subsequently assessed in a randomized trial. Among HIV-1-uninfected women without an acute phase response, a RBP:TTR cut-off value of 0.25 had approximately 80% sensitivity and specificity to detect vitamin A deficiency (retinol <0.70 micromol/L). No RBP:TTR cut-off value demonstrated both high sensitivity and specificity among HIV-1 infected women without evidence of inflammation. HIV-1 infection and advanced HIV-1 disease were associated with higher RBP:TTR ratios. The effect of HIV-1 was independent of the acute phase response, which also increased the RBP:TTR ratio. Serum retinol increased with vitamin A supplementation among those with a low RBP:TTR ratio, although the effect was small and was not present among those with concurrent inflammation. Thus, the RBP:TTR ratio has modest ability to predict vitamin A deficiency among healthy adults, but HIV-1 infection alters the ratio, even in the absence of the acute phase response. Our results raise questions about the utility of this measurement given the high prevalence of HIV-1 infection in areas where vitamin A deficiency is common.     

Exploring Reticular Pseudodrusen Extent and Impact on Mesopic Visual Sensitivity in Intermediate Age-Related Macular Degeneration

PurposeTo explore the impact of the extent of reticular pseudodrusen (RPD) on mesopic visual sensitivity in individuals with intermediate age-related macular degeneration (AMD).MethodsIn total, 570 eyes from 285 participants with bilateral large drusen underwent microperimetry testing to assess the visual sensitivity of the central 3.6-mm region and multimodal imaging to determine the extent of RPD in the central 20° × 20° region (at the eye level). Mean visual sensitivity within five sectors in the central 3.6-mm region sampled on microperimetry and the extent of RPD in these sectors were derived. Linear mixed models were used to examine the association between the extent of RPD on overall mean visual sensitivity and sector-based mean sensitivity.ResultsAn increasing extent of RPD at the eye level and within sectors was associated with a significant reduction in overall and sector-based mean sensitivity, respectively (P < 0.001 for both). However, when both RPD parameters were considered together in a multivariable model, only an increasing extent of RPD at the eye level (P < 0.001) and not within each sector (P = 0.178) was independently associated with reduced sector-based mean sensitivity.ConclusionsMesopic visual sensitivity is generally reduced in eyes with large drusen and coexistent RPD compared to eyes without RPD, with greater reductions with an increasing extent of RPD. However, reduced sector-based visual sensitivities are explained by the overall extent of RPD present, rather than their extent within the sector itself. These findings suggest that there are generalized pathogenic changes in eyes with RPD accounting for the observed mesopic visual dysfunction.     

Growing Teratoma Syndrome in the Setting of Sarcoidosis: A Case Report and Literature Review

Growing teratoma syndrome (GTS) is rare and can mimic disease recurrence in patients with a history of immature teratoma. Benign hypermetabolic lymphadenopathy found on staging and surveillance computed tomography (CT) and positron emission tomography (PET) may lead to the presumption of metastatic malignancy. We report a case of a 38 year old with mixed mature and immature teratomas who developed new peritoneal masses after adjuvant chemotherapy despite a normalization of tumor markers. In addition to low FDG uptake observed in these peritoneal masses, a PET scan showed hypermetabolic lymphadenopathy and pulmonary and spleen lesions suggesting widespread metastases. Subsequent surgical resection confirmed a mixed pathology with GTS and sarcoidosis. We reviewed the current literature evidence of GTS and sarcoidosis as a benign cause of lymphadenopathy in cancer patients. We emphasize the importance of a tissue diagnosis before instituting therapy for presumed cancer recurrence to avoid potentially fatal diagnostic traps and management errors. A multiple disciplinary team approach is imperative in managing patients with suspected recurrent immature teratomas.