"‘Inert’ Ingredients Are Understudied, Potentially Dangerous to Bees and Deserve More Research Attention

Agrochemical formulations are composed of two broad groups of chemicals: active ingredients, which confer pest control action, and ‘inert’ ingredients, which facilitate the action of the active ingredient. Most research into the effects of agrochemicals focusses on the effects of active ingredients. This reflects the assumption that ‘inert’ ingredients are non-toxic. A review of relevant research shows that for bees, this assumption is without empirical foundation. After conducting a systematic literature search, we found just 19 studies that tested the effects of ‘inert’ ingredients on bee health. In these studies, ‘inert’ ingredients were found to cause mortality in bees through multiple exposure routes, act synergistically with other stressors and cause colony level effects. This lack of research is compounded by a lack of diversity in study organism used. We argue that ‘inert’ ingredients have distinct, and poorly understood, ecological persistency profiles and toxicities, making research into their individual effects necessary. We highlight the lack of mitigation in place to protect bees from ‘inert’ ingredients and argue that research efforts should be redistributed to address the knowledge gap identified here. If so-called ‘inert’ ingredients are, in fact, detrimental to bee health, their potential role in widespread bee declines needs urgent assessment

The Relationship between Tobacco Retailer Density and Neighborhood Demographics in Ohio

Introduction: Studies from various parts of the country suggest that tobacco-related health disparities are exacerbated by disparitiesin the distribution of tobacco retailers (convenience stores, tobacco shops, etc.). The purpose of the present study was to use advancedspatial modeling techniques for count data to estimate current disparities in tobacco retailer density in Ohio.Methods: We identified and geocoded 11,392 tobacco retailers in Ohio. Next, we obtained census tract-level information on race/ethnicity, poverty, and age and obtained county-level information on whether an area was Urban, Suburban, or Rural. Finally, we used negative binomial generalized linear models, adapted for residual spatial dependence, to determine the association between per capita tobacco retailer density and demographic characteristics—summarized by adjusted rate ratios.Results: There were more (from 1.4-1.9 times as many) retailers per capita in high-poverty vs. low-poverty tracts. Poverty also interacted with age: the association between high poverty and high retailer density was stronger for tracts with a low youth population. Density was also greater in tracts with a high (vs. low) prevalence of African Americans (1.1 times as many) and Hispanics (1.2 times as many). Finally, density was generally greater in rural (vs. suburban or urban) tracts, although the effect was modified by a three-way interaction: density was particularly high for rural tracts that also had both a high prevalence of poverty and a low youth population.Discussion: Overall, our findings indicate that Ohio’s vulnerable populations are exposed to a greater per capita density of tobaccoretailers. There is a need for state and local-level tobacco control policies that will improve equity and reduce health disparities

Efficacy of a High-Iron Dietary Intervention in Women with Celiac Disease and Iron Deficiency without Anemia : A Clinical Trial

Background and aim: Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing age in whom the imbalance between menstrual iron loss and inadequate iron intake from their diet plays the major role. A recommended approach to this condition is yet to be established. This study aimed to compare, in this subset of patients, the efficacy of a dietary approach consisting of an iron-rich diet against the traditional pharmacological oral-replacement therapy. Material and methods: Between February and December 2016, consecutive CD female patients of child-bearing age as referred to our outpatient center with evidence of IDWA (ferritin <15 ng/mL or 15-20 ng/L with transferrin saturation <15%) were enrolled. After the completion of a 7-day weighed food intake recording to assess the usual iron dietary intake, the patients were randomized in two arms to receive a 12-week iron-rich diet (iron intake >20 mg/die) versus oral iron supplementation with ferrous sulfate (FS) (105 mg/day). Blood tests and dietary assessments were repeated at the end of treatment. The degree of compliance and tolerability to the treatments were assessed every month by means of specific questionnaires and symptoms evaluation. Results: A total of 22 women were enrolled and divided in the diet group (n = 10, age 37 \ub1 8 years) and in the FS group (n = 12, age 38 \ub1 10 years). The food intake records demonstrated an inadequate daily intake of iron in all the enrolled subjects. At the end of the treatments, ferritin levels were higher in the FS group (8.5 (5) versus 34 (30.8), p = 0.002). Compliance and tolerability were similar in both treatment groups (89% versus 87%, p = ns). Conclusions: These findings did not support any equivalent efficacy of an iron-rich diet compared to a FS supplementation in non-anemic iron-deficient women affected by CD. However, the diet appeared a well-tolerated approach, and adequate dietary instructions could effectively increase the daily iron consumption, suggesting a role in the long-term management of IDWA, especially in patients who do not tolerate pharmacological supplementation

Vulnerability of Subsistence Systems Due to Social and Environmental Change: A Case Study in the Yukon-Kuskokwim Delta, Alaska

Arctic Indigenous communities have been classified as highly vulnerable to climate change impacts. The remoteness of Arctic communities, their dependence upon local species and habitats, and the historical marginalization of Indigenous peoples enhances this characterization of vulnerability. However, vulnerability is a result of diverse historical, social, economic, political, cultural, institutional, natural resource, and environmental conditions and processes and is not easily reduced to a single metric. Furthermore, despite the widespread characterization of vulnerability, Arctic Indigenous communities are extremely resilient as evidenced by subsistence institutions that have been developed over thousands of years. We explored the vulnerability of subsistence systems in the Cup’ik village of Chevak and Yup’ik village of Kotlik through the lens of the strong seasonal dimensions of resource availability. In the context of subsistence harvesting in Alaska Native villages, vulnerability may be determined by analyzing the exposure of subsistence resources to climate change impacts, the sensitivity of a community to those impacts, and the capacity of subsistence institutions to absorb these impacts. Subsistence resources, their seasonality, and perceived impacts to these resources were investigated via semi-structured interviews and participatory mapping-calendar workshops. Results suggest that while these communities are experiencing disproportionate impacts of climate change, Indigenous ingenuity and adaptability provide an avenue for culturally appropriate adaptation strategies. However, despite this capacity for resiliency, rapid socio-cultural changes have the potential to be a barrier to community adaptation and the recent, ongoing shifts in seasonal weather patterns may make seasonally specific subsistence adaptations to landscape particularly vulnerable.Les collectivités autochtones de l’Arctique sont classées comme étant fortement vulnérables aux incidences du changement climatique. L’éloignement des collectivités de l’Arctique, leur dépendance des espèces et des habitats locaux de même que la marginalisation historique des peuples autochtones intensifient cette vulnérabilité. Toutefois, la vulnérabilité est le résultat de conditions et de processus divers sur le plan historique, social, économique, politique, culturel, institutionnel, environnemental et des ressources naturelles. Il est difficile d’attribuer la vulnérabilité à un seul aspect. Malgré cette vaste caractérisation de la vulnérabilité, les collectivités autochtones de l’Arctique sont extrêmement résilientes, comme en attestent les modes de subsistance qui se sont développés au fil de milliers d’années. Nous avons exploré la vulnérabilité des systèmes de subsistance du village cup’ik de Chevak et du village yup’ik de Kotlik du point de vue des dimensions saisonnières fortes de la disponibilité des ressources. Dans le contexte des récoltes de subsistance des villages autochtones de l’Alaska, la vulnérabilité peut être déterminée au moyen de l’exposition des ressources de subsistance aux incidences du changement climatique, de la sensibilité d’une collectivité à ces incidences et de la capacité des institutions de subsistance à absorber ces incidences. Les ressources de subsistance, leur saisonnalité et les incidences perçues de ces ressources ont été étudiées au moyen d’entrevues semi-structurées et d’ateliers participatifs d’établissement de calendrier. Selon les résultats, bien que ces collectivités soient aux prises avec des incidences disproportionnées de changement climatique, l’ingéniosité et l’adaptabilité des Autochtones pavent le chemin à des stratégies d’adaptation convenant à leur culture. Cependant, malgré cette capacité de résilience, les changements socioculturels accélérés ont la possibilité de faire obstacle à l’adaptation collective, sans compter que la variation continue des tendances climatiques saisonnières peut rendre les adaptations de subsistance saisonnières au paysage particulièrement vulnérables

2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance

Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients

Identification of novel pathogenic variants and features in patients with pseudohypoparathyroidism and acrodysostosis, subtypes of the newly classified inactivating PTH/PTHrP signaling disorders.

Albright hereditary osteodystrophy (AHO) is a complex disorder defined by the presence of a short adult stature relative to the height of an unaffected parent and brachydactyly type E, as well as a stocky build, round face, and ectopic calcifications. AHO and pseudohypoparathyroidism (PHP) have been used interchangeably in the past. The term PHP describes end-organ resistance to parathyroid hormone (PTH), occurring with or without the physical features of AHO. Conversely, pseudopseudohypoparathyroidism (PPHP) describes individuals with AHO features in the absence of PTH resistance. PHP and PPHP are etiologically linked and caused by genetic and/or epigenetic alterations in the guanine nucleotide-binding protein alpha-stimulating (Gs α) locus (GNAS) in chromosome 20q13. Another less-recognized group of skeletal dysplasias, termed acrodysostosis, partially overlap with skeletal, endocrine, and neurodevelopmental features of AHO/PHP and can be overlooked in clinical practice, causing confusion in the literature. Acrodysostosis is caused by defects in two genes, PRKAR1A and PDE4D, both encoding important components of the Gs α-cyclic adenosine monophosphate-protein kinase A signaling pathway. We describe the clinical course and genotype of two adult patients with overlapping AHO features who harbored novel pathogenic variants in GNAS (c.2273C > G, p.Pro758Arg, NM_080425.2) and PRKAR1A (c.803C > T, p.Ala268Val, NM_002734.4), respectively. We highlight the value of expert radiological opinion and molecular testing in establishing correct diagnoses and discuss phenotypic features of our patients, including the first description of subcutaneous ossification and spina bifida occulta in PRKAR1A-related acrodysostosis, in the context of the novel inactivating PTH/PTH related peptide signaling disorder classification system.Cambridge NIHR Biomedical Research Centr

Mosaicism for GNAS methylation defects associated with pseudohypoparathyroidism type 1B arose in early post-zygotic phases

BACKGROUND: Pseudohypoparathyroidism type 1B (PHP1B; MIM#603233) is a rare imprinting disorder (ID), associated with the GNAS locus, characterized by parathyroid hormone (PTH) resistance in the absence of other endocrine or physical abnormalities. Sporadic PHP1B cases, with no known underlying primary genetic lesions, could represent true stochastic errors in early embryonic maintenance of methylation. Previous data confirmed the existence of different degrees of methylation defects associated with PHP1B and suggested the presence of mosaicism, a phenomenon already described in the context of other IDs. RESULTS: With respect to mosaic conditions, the study of multiple tissues is a necessary approach; thus, we investigated somatic cell lines (peripheral blood and buccal epithelium and cells from the urine sediment) descending from different germ layers from 19 PHP patients (11 spor-PHP1B, 4 GNAS mutated PHP1A, and 4 PHP with no GNAS (epi)genetic defects) and 5 healthy controls. We identified 11 patients with epigenetic defects, further subdivided in groups with complete or partial methylation defects. The recurrence of specific patterns of partial methylation defects limited to specific CpGs was confirmed by checking methylation profiles of spor-PHP1B patients diagnosed in our lab (n\u2009=\u200956). Underlying primary genetic defects, such as uniparental disomy or deletion, potentially causative for the detected partial methylation were excluded in all samples. CONCLUSIONS: Our data showed no differences of methylation levels between organs and tissues from the same patient, so we concluded that the epimutation occurred in early post-zygotic phases and that the partial defects were mosaics. The number of patients with no detectable (epi)genetic GNAS defects was too small to exclude epimutations occurring in later post-zygotic phases, affecting only selected tissues different from blood, thus leading to underdiagnosis during routine molecular diagnosis. Finally, we found no correlation between methylation ratios, representing the proportion of epimutated cells, and the clinical presentation, further confirming the hypothesis of a threshold effect of the GNAS loss of imprinting leading to an "all-or-none" phenotype

Teaching anatomy in a modern medical course: an integrated approach at Vialba Medical School in Milan

Introduction The course of Anatomy in Vialba Medical School \u2013 University of Milan, integrates systemic, topographic and development anatomy, dissection laboratory, peer-teaching, flipped classroom, clinical correlation to radiology and surgery. Methods An anonymous questionnaire based on a five-point Likert scale was submitted to 162 students who had passed the exam of Anatomy. Students evaluated the importance given during study to morphology, relations and variations of organs, the usefulness of different tools in preparing the exam of anatomy. Finally, the impact of the new design course of Anatomy on students\u2019 progress was assessed. Results The results showed that most of the students found very useful dissections, multimedia sources and 3D virtual models. 3D virtual models, dissections and physical models were indicated as the most important tools that should be available for learning Anatomy; instead, medical imaging received a low score. Students focused the study on morphology and relations between organs much more than anatomical variations. Lastly, students who followed the new design course of anatomy showed a significant better performance when compared to students of the previous academic years, in particular on the anatomy of neck, thoracic and abdominopelvic cavity, and neuroanatomy. Conclusions Our study underlines the positive impact of the integration of traditional methods and innovative solutions in learning anatomy, but also the critical approach to radiologic imaging and anatomical variability

Effects of electroacupuncture on minimum alveolar concentration of isoflurane in anesthetized horses during MRI examination

. Introduction Isoflurane causes dose-dependent cardiovascular adverse effects. Because of the high anesthetic mortality in horses and the risk of onset of postanesthetic myopathy, the reduction of isoflurane requirements appears to be indispensable in minimizing its dose-dependent side effects. Since it was found that the minimum alveolar concentration (MAC) of isoflurane was reduced by electroacupuncture (EA) in dogs, in this study the effects of electroacupuncture on MAC in horses under isoflurane general anesthesia were evaluated. Other descriptive-subjective parameters such as quality of recovery, depth, and stability of anesthetic plane were evaluated. 2. Materials and Methods Fifteen lame adult horses underwent general anesthesia for MRI examination and were randomly assigned into 2 groups. In the first group, 10 horses were treated with EA at acupoints GV1, Bai Hui, GV6, GV8, GV11, GV12, ST36, LI4, and PC6 for 30 minutes at 20 Hz. In the second group, 5 horses were used as control group, without EA. 3. Results EA lowered the MAC of isoflurane by 31.3%: the mean ! SD isoflurane MAC for the EA group was 0.9% ! 0.2%, versus 1.3% ! 0.1% for the control group. There was no significant difference regarding rectal temperature, heart rate, systolic and diastolic arterial pressures, and quality of recovery. Depth and stability of anesthetic plane were significantly shallower in the control group (p " 0.002). 4. Discussion EA decreases the isoflurane requirement in horses undergoing general anesthesia. In conclusion, EA could be considered a valid tool as part of a multimodal anesthetic approach