Contamination and Toxicology

Effect of Individual and Combined Treatments of Pesticide, Fertilizer, and Salt on Growth and Corticosterone Levels of Larval Southern Leopard Frogs ( Lithobates sphenocephala ) Abstract Human activities have introduced a variety of chemicals, including pesticides, fertilizers, and salt, into the environment, which may have deleterious effects on the organisms inhabiting these areas. Amphibians are especially susceptible to absorption of chemical pollutants. To determine the possible combined effects of these chemicals on amphibian development and stress levels, Southern leopard frog (Lithobates sphenocephala) larvae were exposed to one of eight individual or combined treatments of atrazine, ammonium nitrate fertilizer, and sodium chloride salt. Stress levels, indicated by release of the stress hormone corticosterone, were measured premetamorphosis at week 8 of development. Water hormone samples were processed to analyze corticosterone levels. Changes in tadpole growth were determined by surface area measurements taken from biweekly photographs. The combined chemical treatment of atrazine, salt, and fertilizer had a significant interactive effect by increasing stress levels before metamorphosis (p = 0.003). After a month of larval development, tadpoles exposed to ammonium nitrate had larger surface area (p = 0.035). Tadpoles exposed to atrazine had a lower growth rate throughout larval development (p = 0.025) and the lowest number of individuals reaching metamorphosis at 33%. However, the frogs in the atrazine treatment that did successfully metamorphose did so in fewer days (p = 0.002). Because amphibians are exposed to multiple chemicals simultaneously in the environment, assessing the effects of a combination of contaminants is necessary to improve application strategies and ecosystem health.

Concentration, Distribution, and Potential Aquatic Risk Assessment of Metals in Water from Chott Merouane (Ramsar Site), Algeria Abstract In this study, 28 surface water samples were collected from eight different sites throughout the Chott Merouane. Samples were detected by atomic absorption spectrometry for Cd, Co, Cr, Cu, Fe, Ni, Mn, Pb, and Zn. The dissolved metal concentrations (mg/L) ranged from 0.05 to 0.90 mg/L for Cd, 0.13–6.45 mg/L for Co, bDL—2.05 mg/L for Cr, 0.03–0.27 mg/L for Cu, 0.34–7.41 mg/L for Fe, 01.6–4.54 mg/L for Ni, 0.15–1.19 mg/L for Mn, 0.23–5.88 mg/L for Pb, and 0.01–0.28 mg/L for Zn. Compared with U.S. EPA standards and other freshwaters worldwide, the most mean concentration of metals in surface water of this salt lake are higher than the guideline levels of aquatic life. This was further corroborated by results from the water quality indices that Chott Merouane is seriously polluted by metals. The values of the metal pollution index indicated that metal pollution level was Cd > Pb > Ni > Fe > Cr > Cu > Mn > Zn, and those metals belong to moderate or high pollution level. The Nemerow pollution index further indicated that Chott Merouane was suffering from serious metal contamination. Based on geostatistics analyses, generally distributions of these metal contents decreased in the order of the North Chott Merouane ≈ the Northwest Chott Merouane > the Eastern part of Chott Merouane > the South Chott Merouane. The quality of water has drastically deteriorated due to the mixed source of anthropogenic inputs. Therefore, necessary conservation and management measures should be taken to improve the water quality of this Ramsar wetland.

Severe Nitrate Pollution and Health Risks of Coastal Aquifer Simultaneously Influenced by Saltwater Intrusion and Intensive Anthropogenic Activities Abstract Groundwater quality is critical for regional sustainability and human well-beings in coastal regions, because groundwater is an important water resource for these areas facing water scarcity. Anthropogenic activities might induce nitrate pollution, whereas saltwater intrusion could decrease coastal groundwater discharge into sea to subsequently cause the persistent accumulation of pollutants in coastal aquifer. Rare information is available on the nitrate pollution of coastal aquifer under simultaneous influences of saltwater intrusion and intensive anthropogenic activities. This study investigated the distribution, pollution, possible sources, and potential health risks of groundwater nitrate of typical coastal aquifer simultaneously influenced by saltwater intrusion and intensive anthropogenic activities. The average/maximal concentration of groundwater nitrate was 173.70/824.80 mg/L, indicating the severe accumulation of nitrate in the coastal aquifer. Concentrations of nitrate in coastal groundwater were much higher than those in adjacent seawater. Groundwater salinization did not have significant effects on nitrate distribution. Groundwater in 87.6% of sampling sites was not suitable for drinking based on nitrate evaluation criterion. Anthropogenic activities might induce nitrate pollution in approximately 94.7% of sampling sites. Sources, including sewage and manure, soil nitrogen, and ammonium fertilizers, contributed to groundwater nitrate with concentration > 100 mg/L in the study area, whereas sewage and manure were the predominant source affecting groundwater nitrate in 97.5% of sampling sites. Groundwater nitrate exerted unacceptable noncancer health risks for infants, children, teenagers, and adults in more than 87.6% of the study area. Infants and children were the most susceptibly influenced by groundwater nitrate. It is urgent to take effective measures for controlling groundwater nitrate pollution in the study area.

A Comparative Assessment of the Aquatic Toxicity of Corexit 9500 to Marine Organisms Abstract The use of chemical dispersants during oil spill responses has long been controversial. During the Deepwater Horizon (DWH) oil spill, 1.8 million gallons of dispersant, mainly Corexit 9500, were applied in offshore waters to mitigate the human health and coastal environmental impact of surface oil contamination. To evaluate the potential impact of the dispersant on marine life, 18 species, representing important ecological and commercial taxa, were tested using low-energy, dispersant-only water accommodated fractions (WAFs) of Corexit 9500 and standard acute toxicity test methods. All prepared WAFs were analytically characterized. Analyses included the two dispersant markers found in the dispersant and evaluated in samples collected during the DWH Response, dioctylsulfosuccinate sodium salt, and dipropylene glycol n-butyl ether (DPnB). The median lethal and effective concentrations (LC/EC50s) were calculated using a nominal exposure concentration (mg/L, based on the experimental loading rate of 50 mg/L) and measured DPnB (µg/L). Results ranged from 5.50 to > 50 mg/L dispersant and 492 to > 304,000 µg/L DPnB. Species sensitivity distributions of the data demonstrated that taxa were evenly distributed; however, algae and oysters were among the more sensitive organisms. The calculated 5% hazard concentration (HC5) for DPnB (1172 µg/L) was slightly higher than the USEPA chronic criteria of 1000 µg/L and substantially higher than all measured concentrations of DPnB measured in the Gulf of Mexico during the DWH oil spill response.

Persistent Halogenated Organic Pollutants in Surface Water in a Megacity: Distribution Characteristics and Ecological Risks in Wuhan, China Abstract Surface water pollution in megacities is strongly linked to human and environmental health, and surface water quality has deteriorated sharply recently because of increasing persistent halogenated organic pollutant (HOP) concentrations. In the present study, we collected 112 water samples from 14 lakes and 11 drinking water sources in Wuhan, China, and analyzed them for two typical groups of HOPs: polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). The mean values of the ΣPCB concentrations were 4.34 and 10.05 ng L−1 in winter and summer, respectively. For ΣPBDE concentrations, the mean values were 0.88 and 1.53 ng L−1 in winter and summer, respectively. The PCB and PBDE concentrations at most sites in summer were significantly higher than those in winter, probably because of heavy stormwater runoff in summer. The degree of urbanization predicted from the population density was positively correlated with ΣPCB concentrations in the drinking water sources in summer. PBDE and PCB composition analysis suggested the major sources were penta-BDE and Aroclor mixtures. Risk assessments showed the PBDEs in water from the Zhuankou site exceeded the threshold set by the European Union, which could result in adverse effects on aquatic organisms. Negligible noncarcinogenic risks were found for PCBs and PBDEs in the surface water with regard to drinking and bathing. However, the carcinogenic risks of PCBs for bathing in surface water were higher than the safe level of 1.00 × 10−6, implying that the surface water in Wuhan is not safe for bathing.

Perfluoroalkyl Contaminant Exposure and Effects in Tree Swallows Nesting at Clarks Marsh, Oscoda, Michigan, USA Abstract A site in northeastern Michigan, Oscoda Township, has some of the highest recorded exposure in birds to perfluorinated substances (PFASs) in the United States. Some egg and plasma concentrations at that location exceeded the lowest reproductive effect threshold established for two avian laboratory species. The objectives of this study were to determine whether there were reproductive effects or physiological responses in a model bird species, the tree swallow (Tachycineta bicolor), associated with this extremely high exposure to PFASs. The lack of exposure above background to other contaminants at this site allowed for an assessment of PFAS effects without the complication that responses may be caused by other contaminants. A secondary objective was to determine the distribution of PFASs in multiple tissue types to better understand and interpret residues in different tissues. This can best be done at highly exposed locations where tissue concentrations would be expected to be above detectable levels if they are present in that tissue. There were no demonstrable effects of PFAS exposure on reproduction nor on most physiological responses.

The Relationship Between Human Adenovirus and Metals and Semimetals in the Waters of the Rio Doce, Brazil Abstract The 2015 rupture of the Fundão dam near the district of Bento Rodrigues in Mariana, Minas Gerais, Brazil, released around 50 million m3 of iron ore tailings. The first tributary of the Rio Doceto receive this waste was the Gualaxo do Norte River. Many groups in Brazil and from around the world have studied the environmental and social impacts of this disaster. However, relationships between the introduction of mining waste, the geological complexity of the area, and the presence of pathogenic organisms have not yet been investigated. The present study aimed to measure the concentrations of enteric pathogens along the Gualaxo do Norte River after the environmental disaster and to correlate their abundance with the presence of metals and semimetals coming from both mining tailings and geological sources. For this purpose, we collected water samples from 27 stations along the entire basin during a hydrological year. The concentrations of metals and semimetals measured in this study were generally within limits established by national and international legislation, except for those of iron and manganese. Positive correlations between the human adenovirus (HAdV) and arsenic, barium, iron, lead, manganese, and nickel were confirmed, allowing us to observe that there is an abundance of the potentially infectious virus present in the studied sites containing metal/semimetal concentrations. These studies indicate the importance of investigations that consider viral enteric pathogens complexed with metals and may favor the stability and prolongation of the infectivity of such pathogens in water destined for human and animal usage.

The Effects of Selenomethionine on the Escape Behaviours of Fathead Minnows Abstract Selenium (Se) is an essential micronutrient for animals and yet becomes toxic with only a small increase in concentration. Toxicological studies have reported various effects of Se on fishes, including developmental impacts and deformities of the musculature and sensory systems. This paper investigates the impact of sublethal concentrations of Se on the ability of the Fathead Minnow (Pimephales promelas) to perform escape responses, a routine behaviour important to predator–prey dynamics. Predation is among the strongest evolutionary driving forces in nature. Changes to this dynamic can have effects that cascade through the ecosystem. We used responses to mechanical and visual stimuli to determine the impact of environmentally relevant concentrations of dietary selenomethionine on the behaviour of minnows. Latency to respond to the stimulus and kinematic performance were assessed. Our results indicated that there was no significant effect of selenomethionine on either the visual response to a threat or burst swimming behaviours of the fast-start response in minnows. Levels of Se in tissues approached that of tissue-specific guidelines set by regulatory bodies across North America. This suggests that current regulations are adequately protecting this key component of predator avoidance in Fathead Minnows.

Genotoxic Evaluation in Tadpoles Associated with Agriculture in the Central Cerrado, Brazil Abstract Many agricultural practices cause environmental degradation that affects the cellular integrity of anurans. In the present study, we provided in situ data of Dendropsophus minutus, Physalaemus cuvieri, and Scinax fuscovarius collected in soybean/corn and conservation units in the Brazilian Cerrado. The in situ data showed no significant variation in the micronucleus frequency between the sites, only the reniform cells had a higher rate for the agricultural environment. A combined analysis of all nuclear erythrocyte abnormalities (ENAs = nuclear buds, reniform nuclei, apoptotic cell, binucleated, and anucleated cells) was recorded higher frequencies in farmland. Overall, Scinax fuscovarius was considered the best potential bioindicator for soybean/corn plantations. Finally, we recommend expanding the micronucleus test for in situ studies to expand our understanding of the sensitivity of native anuran species and provide a more systematic assessment of the adverse effects of environmental pollutants on wildlife.

Distribution of Organohalogen and Synthetic Musk Compounds in Breast Adipose Tissue of Breast Cancer Patients in Ulster County, New York, USA Abstract We determined the concentrations of 98 halogenated organic compounds and synthetic musks in breast fat tissues of 50 breast cancer patients (age range: 34–77 years) collected during 1996–1998 in Ulster County, New York, USA. Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated biphenyl 153 (PBB-153), polybrominated diphenyl ethers (PBDEs), and synthetic musk compounds (SMCs) were analyzed in breast fat tissues, and 46 analytes were found at a detection frequency of ≥ 65% and at concentrations in the decreasing order of OCPs > PCBs > SMCs > PBDEs > PBB-153. PCBs (median: 323 ng/g wet wt) and dichlorodiphenyltrichloroethanes (DDTs, median: 293 ng/g wet wt) were the major compounds found in breast fat tissues. Among PCB congeners, hexa- and hepta-chlorobiphenyls (60% of total PCBs) were the abundant ones. p,p′-DDE accounted for more than 99% of the total DDT concentrations. The concentrations of SMCs and PBDEs were 1–2 orders of magnitude lower than those of PCBs and DDTs. 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-r-2-benzopyran (median: 33 ng/g wet wt) was the most abundant SMC, whereas BDE-47 (median: 4.5 ng/g wet wt) was the most dominant PBDE congener present in breast tissues. A significant correlation (p < 0.05) between women's age and concentrations of DDTs, chlordanes, hexachlorobenzene and PCBs in breast tissues was found. Concentrations of PCBs, PBDEs, OCPs, and SMCs were not significantly different between malignant and benign tumor cases. This study adds baseline information on target tissue burdens of persistent organic contaminants in breast cancer patients. Graphical Abstract

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Aging

Hospital-acquired acute kidney injury in very elderly men: clinical characteristics and short-term outcomes Abstract Objectives We explored the risk factors for, and the clinical characteristics of, acute kidney injury (AKI), and the causes of death 28 days after such injury, in very elderly men. Methods This was a retrospective cohort study using data from the Geriatric Department of the Chinese PLA General Hospital. A total of 3464 elderly patients (≥ 75 years) were enrolled from January 2007 to December 2015. All patients were followed for 28 days or until death after AKI. Results In total, 668 patients (39.0%) developed AKI, and 623 men were included for the final analysis. The median age was 87 years. The 28-day mortality rate was 25.7%. The AKI etiologies were infections (39.6%), hypovolemia (23.8%), cardiovascular events (15.9%), nephrotoxicity (12.0%), and surgery (7.1%). Multiple organ dysfunction syndrome (46.4%) and pulmonary infection (22.5%) were the principal causes of death. Multivariate analysis revealed that time for AKI to develop (HR = 0.865; 95% CI 0.799–0.937; P < 0.001), low mean arterial pressure (HR = 0.970; 95% CI 0.958–0.981; P < 0.001), low serum prealbumin (HR = 0.924; 95% CI 0.894–0.955; P < 0.001) level, oliguria (HR = 2.261; 95% CI 1.424–3.590; P = 0.001), mechanical ventilation (HR = 1.492; 95% CI 1.047–2.124; P = 0.027), blood urea nitrogen (HR = 1.037; 95% CI 1.025–1.049; P < 0.001) level, magnesium (HR = 2.512; 95% CI 1.243–5.076; P = 0.010) level, and more severe AKI stages (stage 2: HR = 3.709; 95% CI 1.926–7.141; P < 0.001 and stage 3: HR = 5.660; 95% CI 2.990–10.717; P < 0.001) were independent risk factors for 28-day mortality. Conclusions The incidence of AKI increases significantly as age advanced. Identification of risk factors might lead to more intensive monitoring and early prevention, and might improve AKI patients' outcomes in the very elderly.

Internal fixation of intracapsular femoral neck fractures in elderly patients: mortality and reoperation rate Abstract Background A significant increase in the prevalence of intracapsular femoral neck fractures in the elderly population was reported but the best treatment is still debated. Aim To evaluate the mortality rate and the reoperation rate of stable neck fractures treated with cannulated screw fixation in elderly patients. Methods This was a retrospective study of patients older than 60 years with a Garden I or II femoral neck fractures treated with cannulated screw fixation without capsulotomy. A total of 244 patients (246 hips) who underwent surgery between 2008 and 2018 were included. The average age at the time of surgery was 80 years (range 60–99 years). The mean ASA score was 2.64 (range 1–4). Mortality rate, complications, reoperation rate, the time elapsed between surgeries were recorded. Results The mortality rate was 50.0%. There were 16 mortalities (6.6%) in the first-month follow-up. We observed higher mortality rates in ASA 4 (80.8%). In 22 patients (8.9%), complications after surgery were observed, and in 11 patients (4.5%) underwent conversion surgery to hemiarthroplasty at a mean of 14.6 months (range 2–48 months) after the femoral screw fixation. Two patients were treated with hardware removal and Gamma Nail for a peri-implant subtrochanteric femur fracture. Interpretation Cannulated screw fixation should be considered a valid option in intraarticular femoral Garden I–II fractures in elderly patients. Level of evidence Level IV, therapeutic study.

Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson's disease: a meta-analysis Abstract Background Selegiline or levodopa treatment has been suggested as a therapeutic method for Parkinson's disease (PD) in many clinical trial reports. However, the combined effects of two drugs still remain controversial. The aim of this report was to evaluate the clinical efficacy and safety of selegiline plus levodopa (S + L) combination therapy in the treatment of PD compared to that of L monotherapy, to provide a reference resource for rational drug use. Methods Randomized controlled trials (RCTs) of S + L for PD published up to September, 2018 were searched. Mean difference (MD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I2 test. Sensitivity analysis was also performed. The outcomes measured were as follows: the unified Parkinson's disease rating scale (UPDRS) scores, modified Webster score, adverse events and mortality. Results Fourteen RCTs with 2008 participants were included. Compared with L monotherapy, the pooled effects of S + L combination therapy on UPDRS score were (eleven trials; MD − 7.00, 95% CI − 8.35 to − 5.65, P < 0.00001) for total UPDRS score (nine trials; MD − 5.74, 95% CI − 7.71 to − 3.77, P < 0.00001) for motor UPDRS score (seven trials; MD − 1.61, 95% CI − 2.18 to − 1.04, P < 0.00001) for activities of daily living UPDRS score (three trials; MD − 0.38, 95% CI − 0.61 to − 0.14, P = 0.002) for mental UPDRS score. The Webster score showed significant decrease in the S + L combination therapy compared to L monotherapy (four trials; MD − 5.71, 95% CI − 7.11 to − 4.32, P < 0.00001). Compared with L monotherapy, S + L combination therapy did not increase the number of any adverse events significantly in PD patients (ten trials; OR 1.58, 95% CI 0.83–3.00, P = 0.16). Conclusions S + L combination therapy is superior to L monotherapy for the improvement of clinical symptoms in PD patients. Moreover, the safety profile of S + L combination therapy is comparable with that of L monotherapy.

Nutritional profiles of older adults according the Mini-Nutritional Assessment Abstract Background Malnutrition among older adults plays an important role in clinical and functional impairment. Aims The aim of our study was to evaluate all parameters of Mini-Nutritional Assessment (MNA), according to the nutritional status and to define the risk factors that may cause at risk of malnutrition and malnutrition in more detail. Methods One thousand outpatients aged 65 years or older who underwent the Comprehensive Geriatric Assessment (CGA) were included the study. Results A total of 1000 patients (men vs women; 27.1% vs 72.9%), of whom the mean age was 74.30 ± 8.28, were enrolled. We found that 6.6% of patients were malnourished, 31.6% of patients were at risk of malnutrition and 61.8% of patients were well-nourished. The mean MNA score was 23.71 ± 4.19. In patients with malnourished subgroup, the parameters that cause the most loss of points were self-perception of health (87.9%), protein intake (86.4%) and taking at least 3 medications per day (77.3%). At the risk of malnutrition subgroup, protein intake (86.7%), self-perception of health (74.7%) and taking at least 3 medications per day (65.2%) were the three parameters that cause the most loss of points. Discussion In the at-risk and malnourished subgroups, perception of health status, protein intake and taking at least three medications per day were the same MNA parameters that cause the most loss of points, but the rates were different. Conclusions A nutritional intervention should be done as soon as possible in patients who are at risk of malnutrition.

Special Issue Nutrition and Musculoskeletal Health

Impact of frailty status on the cost of drugs and dietary supplements prescribed to nursing home residents: the SENIOR cohort Abstract Background The financial impact associated with drug consumption has been poorly investigated among frail subjects and, specifically, in nursing home settings. Aims To determine the association of the average monthly cost of the drugs and dietary supplements consumed by nursing home residents with their frailty status. Methods This is an analysis of the first follow-up year of the SENIOR cohort. All participants were classified into "frail" or "non-frail" categories according to Fried's criteria at baseline. Monthly bills from the pharmacy were analysed to determine the association between the average monthly cost of the drugs and dietary supplements consumed and frailty status. Results A sample of 87 residents (83.8 ± 9.33 years and 75.9% women) from the SENIOR cohort was included. The prevalence of frailty was 28%. The median number of medications consumed each day was 9 (6–12) (no difference between frail and non-frail subjects; p = 0.15). The overall median monthly cost was € 109.6, of which 49% was covered by Belgian social security and the remaining balance was paid by the patient. When comparing the drug expenses of the frail subjects and the non-frail subjects, the overall average monthly cost did not differ between the 2 groups (p = 0.057). Nevertheless, the expenditure remaining to be paid by the residents, after the Belgian social security intervention, was significantly higher among the frail residents (€ 65.7) than among the non-frail residents (€ 47.6; p = 0.017). Conclusions Frailty status has an impact on the expenditures related to the consumption of drugs.

Nutritional influence on bone: role of gut microbiota Abstract Gut microbiota (GM) located within the intestinal tract lumen comprises the largest number of cells (10E14) in the human body. The gut microbiome refers to the collection of genomes and genes present in gut microbiota. GM can vary according to age, sex, genetic background, immune status, geography, diet, prebiotics, which are non-digestible fibers metabolized in the distal part of the gastrointestinal tract, probiotics, which are micro-organisms conferring a health benefit on the host when administered in adequate amounts, living conditions, diseases and drugs. A source of probiotics is fortified fermented dairy products, which in addition provide calcium, protein, phosphorus and various micronutrients. Bone homeostasis is influenced by GM composition and/or products. GM appears to be a major player in the various determinants of bone health. However, it remains to be demonstrated in well conducted long-term randomized controlled trials, whether interventions changing GM composition and/or function are capable of reducing fracture risk.

Supplemental calcium intake in the aging individual: implications on skeletal and cardiovascular health Abstract Adequate calcium intake during childhood is necessary to achieve optimal peak bone mass and this has the potential by increasing bone reserves, to modulate the rate of age-associated bone loss. However, data regarding the efficacy of calcium obtained either through the diet or in the form of medicinal supplementation, for prevention of bone loss and osteoporotic fractures in the elderly is conflicting. Calcium alone is unlikely to be of benefit for this purpose though the co-administration of calcium and vitamin D may have modest fracture risk benefits. Supplemental calcium with or without vitamin D has recently come into the spotlight after the publication of the findings from a controversial randomized controlled trial that associated calcium supplementation with an increased risk of myocardial infarction. Since then, multiple studies have explored this potential link. The data remains conflicting and the potential mechanistic link if any exists, remains elusive. This review examines the relationship between supplemental calcium intake and skeletal and cardiovascular health in the aging individual through an appraisal of studies done on the subject in the last three decades. It also briefly details some of the studies evaluating fractional absorption of calcium in the elderly and the rationale behind the current recommended dietary allowances of calcium.

The role of omega-3 in the prevention and treatment of sarcopenia Abstract Sarcopenia is a geriatric syndrome with increasing importance due to the aging of the population. It is known to impose a major burden in terms of morbidity, mortality and socio-economic costs. Therefore, adequate preventive and treatment strategies are required. Progressive resistance training and protein supplementation are currently recommended for the prevention and treatment of sarcopenia. Omega-3 polyunsaturated fatty acids (PUFAs) might be an alternative therapeutic agent for sarcopenia due to their anti-inflammatory properties, which target the 'inflammaging', the age-related chronic low-grade inflammation which is assumed to contribute to the development of sarcopenia. In addition, omega-3 PUFAs may also have an anabolic effect on muscle through activation of the mTOR signaling and reduction of insulin resistance. This narrative review provides an overview of the current knowledge about omega-3 PUFAs and their role in the prevention and treatment of sarcopenia. We conclude that there is growing evidence for a beneficial effect of omega-3 PUFAs supplementation in sarcopenic older persons, which may add to the effect of exercise and/or protein supplementation. However, the exact dosage, frequency and use (alone or combined) in the treatment and prevention of sarcopenia still need further exploration.

The effects of calorie restriction, intermittent fasting and vegetarian diets on bone health Abstract Uncountable health care organizations, clinicians, and individuals are striving to prevent obesity and the many chronic medical conditions linked to it by advocating a healthy lifestyle that includes measures such as reducing dietary calorie intake (i.e., calorie restriction = CR and intermittent fasting = IF) or limiting/abolishing animal source foods (i.e., practices termed vegetarianism and veganism). Although these regimens are traditionally considered healthy, their real impact on bone health has yet to be established, and some studies have reported that they have negative effects on bone outcomes. The current work provides an overview of the studies carried out to examine the effect/s of CR, IF and vegetarian/vegan diets on bone health, and, in particular, on bone mineral density (BMD) and fracture risk. Although data on this subject are limited to small studies and there is no information specifically referring to fractures, CR, but not IF, seems to reduce BMD but does not seem to affect bone quality. Vegetarian diets (particularly vegan ones) are associated with significantly lower BMD values with respect to omnivorous ones and could, potentially, increase the risk of fractures. Given these considerations, individuals who decide to follow these diets should be aware of the risk of osteoporosis and of bone fractures and should introduce dietary sources of calcium and Vitamin D and/or supplementation. Future studies examining fracture/osteoporosis incidence in selected populations will be able expand our knowledge about the safety of these diets and the risks linked to them.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Voluntary and Nonprofit Organizations

Dennis R. Young, Elizabeth A. M. Searing, Cassady V. Brewer (Eds.): The Social Enterprise Zoo

Dey, Pascal & Steyaert, Chris (Ed.): Social Entrepreneurship. An Affirmative Critique. Cheltenham UK: Edward Elgar Publishing Ltd., 2018, pp. 328, £85.50 (Hardback)

Dennis Young: Financing Nonprofits and Other Social Enterprises: A Benefits Approach

Bruce A. Seaman and Dennis R. Young: Handbook of Research on Nonprofit Economics and Management

Distinctions Between Non-profit, For-profit, and Public Providers: The Case of Multi-sector Rental Housing Abstract Although various organizational forms are involved in the critically important role of providing rental housing, little is known about their potentially distinctive characteristics. Calling upon unique data collected from landlords and tenants of for-profit, non-profit, and public rental housing in Canada (N = 5624 units; N = 492 tenants), we explore shelter costs paid by tenants, quality, and unit accessibility. Findings point to some unique features based on provider type: non-profits have lower shelter costs than for-profit units, and for-profit and public status are associated with lower odds of accessibility. Limited differences are found related to housing quality.

What Does China's Twin-Pillared NGO Funding Game Entail? Growing Diversity and Increasing Isomorphism Abstract Two trends are gaining prevalence across China: (1) NGO needs for funding in order to survive and (2) the transformation of the government and private foundations into major NGO donors. This study explores grassroots NGOs' experience with the government's purchase-of-services contracting and private foundations' grant schemes in Shanghai, Beijing and Sichuan. The research findings show that two opposite effects of the funding game are simultaneously felt: growing space for diversity and increasing isomorphic pressures. The two donor types have jointly created a result-driven and institutionalized environment in which NGOs easily lose sight of their missions and uniqueness. Nonetheless, despite finding their options extremely limited, NGOs adopt constantly evolving, multifaceted resource strategies.

Purpose, Commitment and Coordination Around Small Wins: A Proactive Approach to Governance in Integrated Hybrid Organizations Abstract Integrated hybrid organizations, for instance social enterprises that pursue both social and economic goals through a single activity, are seen by many as promising vehicles to create social value while remaining economically sustainable. At the same time, they are said to run the risk of mission drift—losing sight of their social mission while navigating market and political pressures. While organizational governance mechanisms that ensure the overall direction, control and accountability of the organization are considered key to avoiding mission drift, scholars have argued that traditional governance mechanisms may not work in the context of social enterprises. Drawing on the legacy of old institutional theory, this article proposes a proactive approach to governance in social enterprises. We complement and go beyond control and compliance approaches and introduce a governance approach focused on purpose, commitment and coordinating around small wins. We propose that these three interlocking governance mechanisms allow social enterprises to mitigate the risk of mission drift in a proactive rather than reactive manner.

Developing the Potential for Change: Challenging Power Through Social Entrepreneurship in the Netherlands Abstract Most research on social entrepreneurship overemphasizes agency by presenting social enterprising as something that originates solely from the intrinsic motivations of individual entrepreneurs. Research that does regard the impact of state power is almost exclusively anchored in and geared toward neoliberal policy contexts. This article examines the dialectics between state power and entrepreneurial counterpower in the institutional context of the Netherlands. Moreover, since social entrepreneurs develop different tactics and strategies for responding to challenges, we use Gaventa's power cube to distinguish forms of power and counterpower, which we then combine with the following inductively derived social entrepreneur typologies: successful hybrids, antagonistic organizers, and autonomous entrepreneurs. This offers insights into the development of theory in relation to the social entrepreneurial potential for change and civic participation.

Managing Organizational Paradoxes in Social Enterprises: Case Studies from the MENA Region Abstract This study aims to examine the question around how small- and medium-scale hybrid social enterprises within the context of the Middle East and North Africa manage paradoxical tensions they face in their everyday decision-making. By placing a lens on the unique hybrid processes facing organizational members rooted in traditional social and economic rationales, we seek to better understand the breadth of strategies adopted and their relevance to the specific contextual considerations of the study. Through analyzing five in-depth case studies from the region, the study aims to add insights on the practice of managing organizational paradoxes to maintain social-economic hybridity. We also introduce practical implications for managers and supporters of small- and medium-scale social enterprises.

Before Nonprofit Organisations Become Social Enterprises Abstract In the context of weak global economic growth, the transformation of nonprofit organisations (NPOs) into social enterprises is perceived as a critical process of social innovation and sustainable development. This study explored the antecedents and their influences on the social entrepreneurial intentions (SEIs) of NPO workers. Two sets of samples were collected through online surveys. First, 200 samples were used for exploratory factor analysis, and subsequently, 602 samples were used to establish a structural equation model. The results revealed that the involved antecedents partially influenced SEIs through social entrepreneurial (SE) creativity. The originality aspects of SE creativity demonstrated dominant positive effects on both the SE conviction and the SE preparation of SEIs, followed by cognitive empathy and bonding social capital. The stockholder perspective of social responsibility and affective empathy negatively affected both the conviction and preparation of SEIs. The stakeholder perspective of social responsibility and the usefulness aspect of SE creativity demonstrated minor positive effects on SE conviction. We suggest that NPO leaders keep an open mind to business strategies and focus on SE originality, cognitive empathy, and bonding social capital when developing talent for future achievement.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Law and Critique

Introduction

Against Exclusion: Teaching Transsystemically, Learning in Community Abstract In September 2018 the University of Victoria Faculty of Law on Vancouver Island, Canada welcomed its first cohort of students to its cutting edge and innovative joint degree programme in Canadian Common Law (Juris Doctor (JD)) and Indigenous Legal Orders (Juris Indigenarum Doctor (JID)). The JD/JID programme draws on the law faculty's more than two decades of experience and research on Indigenous legal orders, and Indigenous legal education. It is the first of its kind in the world, combining intensive study of Canadian Common Law with rigorous engagement with Indigenous law. The rationale behind this programme is to engage with Indigenous legal orders using the depth, rigour, and critical focus that law schools bring to the study of other legal orders. Pushing against exclusion happening in higher education throughout the Commonwealth and beyond, the JD/JID programme aims to ensure that education in Indigenous Law is no longer an education in exclusion and displacement. This short piece provides necessary background to the programme, including structure and content, and details its transsystemic pedagogical and community-based learning approaches.

Regulatory Threats to the Law Degree: The Solicitors Qualifying Examination and the Purpose of Law Schools Abstract Two major regulatory changes are affecting the provision of undergraduate legal education in England and Wales. On the one hand, the Qualifying Law Degree is being deregulated, meaning law schools are free to make significant changes to how and what they teach. On the other hand, higher education in England has seen a significant overhaul through the creation of the Office for Students, which treats students as consumers. Now more than ever, law schools need to ask themselves existential questions which will not only test their continued relevance or indeed viability within the 'market' for higher education, but also the status of the discipline of law as a whole. The regulatory landscape may indeed present a significant threat, but it is also an opportunity to reflect on what law schools are for, and consequently what changes could result from the academic freedom that comes with deregulation. Whilst different law schools will interpret their mission differently, they should caution against either generalised inertia or succumbing to an outcomes-oriented provision that simply prepares students for the new Solicitors Qualifying Examination. Instead, law schools will find their proper purpose in critical reflection and academic self-grounding, providing undergraduate students with a 'question everything' mentality, and showing them that law is something to be experienced and not merely learnt.

On the Undecidability of Legal and Technological Regulation Abstract Generally, regulation is thought of as a constant that carries with it both a formative and conservative power, a power that standardises, demarcates and forms an order, through procedures, rules and precedents. It is dominantly thought that the singularity and formalisation of structures like rules is what enables regulation to achieve its aim of identifying, apprehending, sanctioning and forestalling/pre-empting threats and crime or harm. From this point of view, regulation serves to firmly establish fixed and stable categories of what norms, customs, morals and behaviours are applicable to a particular territory, society or community in a given time. These fixed categories are then transmitted onto individuals by convention, ritual and enforcement through imperatives of law (and technology) that mark certain behaviours as permissible and others as forbidden, off bounds. In this manner, regulation serves a programming (i.e., a calculable or determinable) purpose. It functions as a pro-active management or as a mastery of threats, risks, crimes and harms that affect a society and its security both in the future and in the present. Regulation for instance, will inscribe and codify what it determines to constitute crime or harm such as pornography, incitement of terrorism, extremist speech, racial hatred etc. These determined or calculated/calculable categories will then be enforced and regulated (e.g. through automated filtering) in order to ensure a preservation of public order within society. Drawing mainly from deconstruction, this article situates law and technologies within a wider ecological process of texts, speech and writing i.e., communication. In placing regulation within disseminatory and iterable processes of communication, this article complicates, destabilises and critiques the dominant position of determinability and calculability within the regulatory operations of law.

The Contradictions of Conscience: Unravelling the Structure of Obligation in Equity Abstract Conscience rests within the heart of equity, yet it is a manifestly nebulous and contradictory concept. In particular, equity has never been clear about exactly whose conscience we are concerned with: the Chancellor or judge, or the court, or the defendant? Furthermore, in some lights conscience appears to compel obedience to the authority of law, whilst in others it gives expression to ethical drives that escape the formal strictures of legal rules. Contextualised within the broader history of ideas of Western modernity, this article sets out to understand the rhetorical significance of conscience in equity, making the argument that its disparate and contradictory modes of expression do not undermine its significance, and instead are essential to its construction of juridical obligations. By invoking conscience as a contradictory expression of both vertical state authority and personal ethical autonomy, equity asserts not only a unique normative structure, but also a distinct mode of power.

Property and the Interests of Things: The Case of the Donative Trust Abstract Within a liberal, 'law of things' understanding of property, the donative trust is seen as a species of gift. Control over trust property passes from the hands of settlors to beneficiaries, from owners to owners. Trust property, like all other property, is silent and passive, its fate determined by its owners. This article questions this understanding of the trust by showing how beneath the facade of ownership, the trust inverts the relation between owner and owned, person and thing. It analyses the relation that trustees, beneficiaries and settlors have to the trust property and argues that the role of each of these parties can be shown to consist in furthering the interests of the trust property rather than their own. It claims that this protects things from their owners at the same time as it ensures these owners' ongoing care towards the things they own. This raises questions about the trust's status within the institution of private property, justified as it is by the human autonomy it is said to enable.

Legal Education Beyond the Academy: The Neoliberal Reorientation of Public Legal Education Abstract In order to re-make the world in its own image, neoliberal expansionism is predicated on the dominance of a particular regime of reason. The dominance of economic-juridical rationality relies in no small part on education to reproduce itself. In this sense, how and why a populace is educated in the law becomes a locus of struggle and of alternative and competing constructions of normative and political orders. Over the last decade the United Kingdom's justice policy has become more attentive to the role of citizens' knowledge of the law in the context of a reinvigorated drive toward competition in the legal services market. Reformism in legal services thereby emerges as a strategy geared toward the economisation of the state by propagating specific types of legal knowledge. This reorientation of legal education is considered through, on the one hand, the insights of recent theories of neoliberalism and, on the other, a wider lens relating the intersection of legal education to the juridical-political realm. Finally, the paper outlines alternative strategies of community-based educational practices rooted in resistance to legal and economic orthodoxies.

Limits to the Politics of Subjective Rights: Reading Marx After Lefort Abstract In response to critiques of rights as moralistic and depoliticising, a literature on the political nature and contestability of rights has emerged. In this view, rights are not merely formal, liberal and moralistic imperatives, but can also be invoked by the excluded in a struggle against domination. This article examines the limits to this practice of rights-claiming and its implication in forms of domination. It does this by returning to Marx's blueprint for the critique of subjective rights. This engagement with Marx will, however, take a particular form. I will read Marx first through the eyes of Claude Lefort and thereafter against Lefort. The latter's critique of Marx still constitutes the strongest case against the dismissal of subjective rights. Introducing a reading of Lefort into the argument allows us to discover what is dead and what is well alive in the Marxist theory of rights. What is dead, I will argue, is Marx's early conception of subjective rights as ideology and illusion. However, the more mature Marx developed a theory and critique of the legal form that is able to explain why the politics of rights—despite its undeniable advances—has not been able to overcome certain forms of domination.

Policies, Technology and Markets: Legal Implications of Their Mathematical Infrastructures Abstract The paper discusses legal implications of the expansion of practical uses of mathematics in social life. Taking as a starting point the omnipresence of mathematical infrastructures underlying policies, technology and markets, the paper proceeds by attending to relevant materials offered by general philosophy, legal philosophy, and the history and philosophy of mathematics. The paper suggests that the modern transformation of mathematics and its practical applications have spurred the emergence of multiple useful technologies and forms of social interaction but have impoverished access to meanings originating in the lifeworld. The paper also argues that, as part of devices of interest aggregation and expert networks, mathematical infrastructures can be scrutinized by a revised form of legal practice that subjects them to legal critique and reconstruction in order to overcome conditions that have eroded the moral self-awareness of individuals and communities and their existential meanings.

From Social Uprising to Legal Form Abstract Does, or should, social uprising lead to new legal form? Ukraine's current situation following the Revolution of Dignity in 2013–2014, with continuing violent conflict in Donbas and Crimea, suggests that not only is it unclear how a 'new' form is assessed, but existing transitional policies and frameworks are unlikely to be clearly implemented and enforced. An alternative analysis of transformation is necessary to address the conflicting aftermath of uprising within a particular historical and cultural context. The transformation that is happening in Ukraine is a continuum that is intellectual and psychological as much as reforming judicial systems and governance. Thinking transformation differently opens onto narratives, complexity of causes and a plurality of ideas of future, resolutions and justice. Such a shift in thought and analysis, informed by narratives and grounded research, is necessary in order to try to understand the current pursuit of justice in Ukraine.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Acta Medica

Validating biological research: Role of statistics Sanjeev Kumar Jain, Umme Afifa, Sanya Jain, Sonika Sharma Acta Medica International 2019 6(1):1-1

A comparative study of histopathological findings in psoriatic lesions with and without treatment Deepti Arora, Faiyaz Ahmad, Ankita Mittal, Ashutosh Kumar, Seema Awasthi, Shyamoli Dutta Acta Medica International 2019 6(1):2-6 Background: Psoriasis is a multifactorial chronic relapsing inflammatory dermatological disorder associated with significant comorbidities. It is characterized by sharply demarcated, erythematous papules, and plaques with abundant silvery-white scales. Due to its variable clinical presentation, histopathology remains the mainstay of diagnosis. However, these histologic features changes with treatment and may also guide in therapeutic decision-making. Aim: The aim is to evaluate and compare the histopathological features of psoriatic lesions before treatment with those receiving treatment for psoriasis. Patients and Methods: A total of 101 biopsies from selected consecutive patients of histopathologically confirmed psoriasis vulgaris were included in the study. These cases were then divided into two groups, Group A includes cases who never received treatment and Group B, those receiving treatment for psoriasis. These biopsies were histopathologically analyzed and compared for various morphological features. Results: Of 101 cases of psoriasis, 72 cases were included in Group A and 29 were included in Group B. Biopsies of Group A showed parakeratosis and acanthosis as a common feature in all of them with dilated or abnormal capillary pattern in dermal papillae in 93.1%. In Group B, in spite of uniform parakeratosis as noticed in Group A biopsies, focal parakeratosis was seen in 83.3%, acanthosis in 87.5%, and dilated/abnormal capillary pattern in dermis was observed to be a universal feature in biopsies of Group B. All other microscopic features of psoriasis also decreased in frequency in Group B. However, statistically significant difference is seen only in changes in morphological features of superficial epidermis that is, parakeratosis, acanthosis, and absent or decreased granular layer in both the groups. Conclusion: Treatment may lead to improvement in the histologic features in epidermis with significant difference in few of them. However, abnormal vasculature in the dermal papillae persists and does not show any improvement with therapy.

Lymph node biopsies: Evaluation of disease pattern and role of surgery – Our experience from South Punjab, Pakistan Muhammad Irshad Hussain, Mulazim Hussain Bukhari, Muhammad Zeeshan Aftab Acta Medica International 2019 6(1):7-10 Objective: The objective of the study was to determine the frequency of different pathologies presenting with lymphadenopathy in patients from South Punjab and to evaluate the role of surgery in reaching the diagnosis. Materials and Methods: It was a cross-sectional study done at Recep Tayyip Erdogan Hospital, Muzaffargarh (managed by The Indus Health Network), from August 2014 to October 2017. Those being biopsied at some other hospital and the lymph node dissection biopsy done for a known primary cancer were excluded. Results: Lymph node biopsy was done on a total of 71 patients (56.3% n = 40 males, 43.7% n = 31 females). The mean (standard deviation) age of the patients was 27.30 ± 17.07 years. Open biopsy was performed on 70 cases (98.6%), whereas laparoscopic biopsy was performed on one case (1.4%). The most common pathology found on histopathology report was Tuberclosis (TB) lymphadenitis (49.3%, n = 35), followed by lymphoma (25.4% – Hodgkin's disease [HD] 15.5% and non-Hodgkin's lymphoma [NHL] 9.9%). Conclusion: TB is the most common pathology, followed by lymphoma. HD is more common than NHL. Surgical biopsy is the gold standard. Laparoscopy and other minimally invasive techniques are very safe and useful for excision biopsy of the central lymph nodes.

Thyroid-stimulating hormone in hypothyroidism – How high is too high? Ruth Priya Senthiappan, Smitha Bhat, Sudeep Krishna Acta Medica International 2019 6(1):11-16 Background: The prevalence of hypothyroidism in the developed world is about 4-5% and in India is 10.9%. The goal of treating hypothyroidism is to maintain thyrotropin (TSH) levels within the normal reference range. Studies have shown that even within the normal range of TSH, patients with low normal TSH (LNT) have better outcomes when compared to patients with high normal TSH (HNT). Aims and Objectives: Our study aimed to find whether patients treated at a dose of levothyroxine resulting in an LNT had improved clinical outcomes and biochemical parameters, when compared to those on a levothyroxine dose resulting in an HNT. Materials and Methods: 180 patients with hypothyroidism on treatment, who had a TSH of 0.27-4.2mIU/L and had been on treatment with a stable dose of at least 50 micrograms of levothyroxine for at least 6 months were administered the Thyroid Symptom Questionnaire. TSH was assayed. Blood pressure and BMI were measured. Serum lipids were measured by spectrophotometry. Results: We found that patients with LNT and HNT did not differ with respect to cognitive symptoms , feelings of coldness, lethargy and fatigue. However, patients with LNT had a better lipid profile (mean LDL 132.24 in HNT and 115.39 in LNT p= 0.08) and lower BMI (1.045kg/m 2 lower in LNT compared to HNT) compared to HNT. Conclusion: Treating patients with a dose of thyroxine titrated to achieve LNT might decrease the cardiovascular risk by improving the lipid profile and BMI.

Acceptance of immunization by caregivers of children attending a tertiary health facility in Northwestern Nigeria Ibrahim Aliyu, Abdulsalam Mohammed, Halima Umar Ibrahim, Yohanna Bitrus Ghidazuka Acta Medica International 2019 6(1):17-21 Introduction: Immunization against childhood diseases is well received in most developed countries; also, countries in the Caribbean and Latin America have attained over 90% immunization coverage unlike the most sub-Saharan African countries, such as Nigeria, which have a dismally low coverage. Our objective is, therefore, to determine the acceptance and willingness to complete immunization of children by caregivers seen in our health facility. Materials and Methods: This study was cross sectional involving caregivers attending the pediatric outpatient clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, during the month of December 2017. This was questionnaire based and was administered by the researchers and trained assistants. It contained 20 questions consisting of both open- and close-ended questions. Results: All respondents were aware of the childhood immunization program and were willing to accept all vaccines for their children. They all believed that immunization was beneficial to their children; 126 (79.7%) respondents could correctly state the advantages of childhood immunization. However, only 18 (11.4%) of the respondents could correctly list the names of the childhood vaccines in the National Programme of Immunization. About 33.5% of respondents reported six visits as the total number of visits for childhood immunization; higher proportion of health workers and those with tertiary educational qualification could correctly list the names of the vaccines given to their children, and these observations were statistically significant (Chi-squared test = 27.786, df = 1, P = 0.000; Fisher's exact test = 12.421, P = 0.004). Conclusion: This study showed that most respondents were willing to accept and complete the immunization schedule; however, there was a significant knowledge gap, especially in listing the names of the vaccines and the expected number of immunization visits.

The jefferson scale of physician empathy: A preliminary study of validity and reliability among physicians in Nigerian tertiary hospital Juliet Hodo Osim, Emmanuel Aniekan Essien, Joseph Okegbe, Owoidoho Udofia Acta Medica International 2019 6(1):22-27 Introduction: Physician empathy has been shown to have a substantial effect on doctor–patient relationship, therapeutic adherence, and overall treatment outcome. Despite its important role, physician empathy is under-researched in Nigeria. Aims: This study aims to investigate the validity and reliability of the Jefferson Scale of Physician Empathy (JSPE) (Health Professional version) among Nigerian physicians in the University of Uyo teaching hospital, Uyo, Nigeria. Participants and Methods: In this cross-sectional study, a brief sociodemographic questionnaire, the Emotional intelligence scale (EIS), and the JSPE were administered to 120 doctors in the University of Uyo teaching hospital. Data were analyzed using SPSS version 22. Results: Cronbach's and split half coefficients were 0.73 and 0.66, respectively. Correlation coefficient with the EIS was 0.49 (P < 0.05). Exploratory factor analysis yielded three factors that were not quite consistent with previous reports. We found empathy to be significantly higher among older physicians, those who were involved in administrative duties and those with a higher rank (P < 0.05). After regression analysis, age, sex, and administrative role emerged as significant predictors of physician empathy (P < 0.05). Conclusions: The JSPE had fairly strong reliability coefficients and an acceptable convergent validity with the EIS which measures a related construct. It can serve as a useful measure of patient-related empathy among Nigerian doctors.

Personality traits of young men with different diplotypes Pavel N Ermakov, Elena V Vorobyeva, Ekaterina M Kovsh, Irina V Abakumova, Olga D Fedotova, Marina P Aralova, Wladimir W Latun, Lubov Ya Horonko Acta Medica International 2019 6(1):28-32 Background: Historically in psychogenetic research the attention has been paid to describing personality traits of the carriers of some sole genotypes; but in this work the characteristic traits of carriers of catecholaminergic system MAOA and COMT genes' genotypes different combinations are presented. Methods: A psychodiagnostic toolkit included 7 types of inventories. Genotyping was conducted with the help of DNA extraction from the buccal epithelium cells with subsequent PCR diagnostics and 3 types of statistical processing. Results: It was shown that carriers of a highly active diplotype have the lowest level of aggressiveness and are inclined to cooperate in the conflict; carriers of the highly active genotype MAOA in combination with the heterozygous genotype COMT have an average level of aggressiveness and high rates of emotional lability; carriers of low-level MAOA in combination with heterozygous genotype COMT have the highest rates of motivation to achieve success and verbal aggression; carriers of low-level MAOA and highly active COMT are emotionally labile and non-aggressive. Conclusion: We conclude that male carriers of a low-active diplotype have the highest level of aggressiveness and disposition to addictive behavior, which may indicate the association of this diplotype in a sample of young Russian men with social disadaptation.

Bedroom design orientation and sleep electroencephalography signals Amin Hekmatmanesh, Maryam Banaei, Khosro Sadeghniiat Haghighi, Arezu Najafi Acta Medica International 2019 6(1):33-37 Background: Orientation is a significant factor in architectural design that may affect well-being. Body direction does not change during sleeping, and sleeping is sensitive and affected by environmental factors. Aims: This neuroarchitecture study aimed to assess the effects of bed orientation on sleep quality to enhance bedroom design. Materials and Methods: To do so, the effects of earth's electromagnetic field (EMF) on sleep electroencephalography (EEG) signals were evaluated using signal processing techniques. In this cross-sectional study, a total of 21 healthy volunteer participants slept for two consecutive naps, at two rooms with identical interior design and different bed orientations, toward and against earth's EMF in a sleep clinic. Statistical Analysis: In this experiment, discrete wavelet transform extracted five subfrequencies of EEG data as delta, theta, alpha, beta1, and beta2. In addition, the energy signals were computed by measurement of wave frequencies. The mean total sleep time was 1.63 h in North–South (N-S) earth's EMF orientation and 1.38 h in the other direction. Results: t-test results showed significant changes in delta, theta, and alpha frequencies in terms of bed orientation. There was a significant result in the alpha energy ratio over the whole signal energy. Furthermore, there were increases in the average energy of delta, theta, and alpha bands in N-S versus East–West (E-W) bed directions. Conclusions: This study indicated that sleep in N-S direction could be more beneficial than E-W and the sleep EEG signals can be sensitive to earth's EMF. The results show the importance of considering orientation in bedroom design and its benefits on inhabitants' well-being.

Evaluation of "point of care" brain natriuretic peptide level in differentiating between cardiogenic and noncardiogenic acute dyspnea (a hospital-based study) Priyanka Singh, Shubham Prasad, Lalit P Meena, Jaya Chakravarty, Madhukar Rai Acta Medica International 2019 6(1):38-43 Introduction: Acute dyspnea is one of the most common reasons for admission to emergency rooms. It could be due to potentially life-threatening cardiac or respiratory conditions. Differentiation among these three disorders is frequently needed. In the condition of heart failure, where there is clinical need for early and appropriate treatment but no objective method for rapid diagnosis, the potential benefits are enormous for any biomarker that can reliably rule in or rule out this syndrome. Objectives: The objectives of this study are as follows: (i) To evaluate the role of point of care of brain natriuretic peptide (BNP) in acute dyspnea and (ii) To determine the cutoff level of BNP to differentiate between cardiogenic and noncardiogenic causes of dyspnea. Materials and Methods: This was an in-hospital cross-sectional study conducted at a tertiary care center. Patients were evaluated using predetermined performa. All these patients were subjected to routine blood investigations, digital chest X-ray, and 12-lead electrocardiography. At the same time point of care, BNP was done in each patient after obtaining informed written consent. All patients with BNP >100 or clinical suspicion for heart failure underwent two-dimensional echocardiography (ECHO) with color Doppler. Results: A cross-sectional study was conducted on 238 patients presenting with acute dyspnea. Almost all patients with BNP level >415 pg/ml had <45% ejection fraction, but patients with BNP level <415 pg/ml had echocardiographic findings not suggestive of heart failure. Conclusion: This study gives us a reliable cutoff level of 415 pg/ml of BNP which clearly distinguishes between cardiogenic versus noncardiogenic dyspnea.

Treatment-emergent dhat syndrome in a young male with Obsessive–Compulsive disorder: An alarm for medication nonadherence Sujita Kumar Kar Acta Medica International 2019 6(1):44-45 Dhat syndrome refers to a culture-bound syndrome of Southeast Asia, where patients present with anxiety and depressive and somatic symptoms, which they attribute to semen loss. Common presentation of these patients is the passage of semen-like substance in urine. Retrograde ejaculation may cause spermaturia, and patients with firmly held cultural myths related to sexuality may develop features of Dhat syndrome. Here, a patient with obsessive–compulsive disorder on treatment with fluoxetine developed retrograde ejaculation and subsequently features of Dhat syndrome.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

NeuroOncology

Non-NF2 mutations have a key effect on inhibitory immune checkpoints and tumor pathogenesis in skull base meningiomas Abstract Aims Skull base meningiomas represent approximately 25% of all meningiomas, nearly 20% of which are atypical or anaplastic. To date, effective medical treatments for meningiomas are still lacking. Genetic aberrations (TRAF7, KLF4, AKT1, and SMO) and the effects of genetic aberrations on the expression of inhibitory immune checkpoint molecules (PD-L1, IDO, and TDO2) in skull base meningiomas are still unclear. Methods Genetic alterations in the four genes were identified in 92 skull base meningiomas by Sanger sequencing. The expression differences in immune checkpoints between mutant and wild-type (WT) tumors were determined by immunohistochemistry (IHC) and Western blot (WB). Results The four mutations were not concurrently detected in the patients with skull base meningiomas. Among the tumors from the KLF4-mutated group, almost half were petroclival meningiomas. KLF4- and TRAF7-mutated tumors were predominantly secretory meningiomas. SMO-mutated tumors exhibited higher calcification, and half of these tumors were observed in the brain midline. Receiver operating characteristic curve analysis indicated that tumor volume can predict KLF4 and TRAF7 mutation status with high sensitivity and specificity, respectively. The IHC and WB analyses indicated that PD-L1, IDO, and TDO2 levels in tumors with TRAF7 mutations were significantly higher than those in WT tumors. Meanwhile, there was a significant difference in TDO2 between tumors with AKT1 mutations and WT tumors. Specifically, TRAF7 mutations could play a key role in skull base meningiomas by regulating the expression of inhibitory immune checkpoints and thus suppressing immune responses. Conclusions Checkpoint inhibitors may be potential strategies for targeted immunotherapies of these mutant meningiomas.

Super-early initiation of temozolomide prolongs the survival of glioblastoma patients without gross-total resection: a retrospective cohort study Abstract Objective The optimal timing of chemoradiotherapy in patients with newly diagnosed glioblastoma (GBM) remains unclear. In this study, we explored the clinical efficacy of super-early initiation of temozolomide (TMZ) in the treatment interval from surgery to radiotherapy. Methods We retrospectively reviewed the clinical data of 375 patients with GBM in our institution from 2012 to 2018. One hundred and sixty-three patients received super-early TMZ within 7 days after craniotomy based on standard Stupp protocol (super-early group, SEG), while two hundred and twelve patients underwent standard Stupp protocol alone (control group, CG). We performed propensity score matching (PSM) to reduce patient selection bias between the two groups. Results Before PSM, both median progression-free survival (PFS) and overall survival (OS) of patients in SEG were longer than those in CG (PFS 11.5 vs. 9.0 months, P = 0.0384 and OS 23.0 vs. 17.0 months, P = 0.0014). After PSM, the clinical efficacy of super-early initiation of TMZ only remained significant in term of OS, which was further validated in Cox hazard proportional model (HR = 0.583, 95% CI 0.384–0.884, P = 0.011). In the subgroup analysis, patients without gross total resection (GTR) or with O6-methylguanine DNA methyltransferase promoter methylation could benefit from super-early initiation of TMZ in both PFS and OS (P < 0.05). No significant difference of treatment emerging adverse events was observed between the two groups (P > 0.05). Conclusions This retrospective study highlights that super-early initiation of TMZ in newly diagnosed GBM may confer to survival benefit, especially for those without GTR.

LncRNA GAS5 regulates the proliferation, migration, invasion and apoptosis of brain glioma cells through targeting GSTM3 expression. The effect of LncRNA GAS5 on glioma cells Abstract Introduction To investigate the effects of lncRNA GAS5 on the proliferation, migration, invasion and apoptosis of brain glioma cells. Methods The expression levels of lncRNA GAS5 and GSTM3 in normal glial cells (HEB) and glioma cells (U251 and U87) were detected by RT-qPCR and western blot, respectively. Glioma cells were transfected with ctrl vector, pcDNA-GAS5, siRNA ctrl (siNC) or GSTM3 siRNA and the effects of lncRNA GAS5 and GSTM3 on the proliferation, migration, invasion and apoptosis of glioma cells were detected by CCK-8 assay, transwell assay and Caspase 3/7 activity assay, respectively. Results The expression of lncRNA GAS5 was significantly decreased in glioma cell lines U251 and U87 compared with normal glial cells HEB (p < 0.01). In addition, overexpression of lncRNA GAS5 inhibited the proliferation, migration and invasion of U251 and U87 cells, and promoted cell apoptosis as demonstrated by the increased activity of Caspase 3/7. Furthermore, GSTM3 was predicted as a target gene of lncRNA GAS5 by bioinformatics analysis and its expression was increased in glioma cells compared with the normal cells as indicated by western blotting and RT-qPCR experimental results. Silencing of GSTM3 with GSTM3 siRNA decreased the proliferation, migration and invasion but increased the apoptosis of glioma cell lines U251 and U87, which was similar to that the effect lncRNA GAS5 over-expression. Conclusion lncRNA GAS5 can effectively inhibit the proliferation, migration and invasion of glioma cells and promote cell apoptosis through targeting GSTM3 expression.

Correction to: Phase I-II trial of imatinib mesylate (Gleevec; STI571) in treatment of recurrent oligodendroglioma and mixed oligoastrocytoma. North central cancer treatment group study N0272 (ALLIANCE/NCCTG) The last author's first name was truncated in the initial online publication. The original article has been corrected.

Radiotherapy for recurrent intracranial epidermoid cysts without malignant transformation: a single-institution case series Abstract Introduction Recurrent intracranial epidermoid cysts may be difficult to address surgically given their proximity to critical neurovascular structures of the skull base. There are emerging reports of using radiotherapy (RT) for the treatment of recurrent epidermoid cysts. Here, we report a case series of adjuvant fractionated external beam RT for recurrent intracranial epidermoid cysts. Methods A single-institution review of all recurrent epidermoid cysts treated with adjuvant therapy between 2000 and 2017 was performed. Results Eight patients with recurrent epidermoid cysts who underwent adjuvant external beam RT were identified. Average age at initial diagnosis was 42.2 years, and median clinical follow-up after initial diagnosis and RT was 16.4 and 2.9 years, respectively. The median number of surgical resections prior to RT was 3 (range 2–5). Rationale for RT included multiple recurrent disease, rapid recurrence following prior resection, increased risk of further surgical morbidity, and patient preference. Median dose was 50.4 delivered in 1.8 Gy fractions (median 28 fractions). By the date of last follow-up, no patient has demonstrated progression, and there have been no cases of malignant degeneration. Conclusion Adjuvant RT should be considered in the context of recurrent epidermoid cysts to decrease the likelihood of further recurrences.

Identification of PEPT2 as an important candidate molecule in 5-ALA-mediated fluorescence-guided surgery in WHO grade II/III gliomas Abstract Purpose 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) appears to be a promising treatment for glioma. However, 5-ALA-mediated fluorescence cannot always be detected in grade II/III gliomas. We hypothesized that gene expression patterns in the Protoporphyrin IX (PpIX) synthesis pathway may be associated with intraoperative fluorescence status of grade II/III gliomas, and then attempted to identify the key molecule of 5-ALA-mediated fluorescence. Methods Using 50 surgically obtained specimens, which were diagnosed as grade II and III gliomas, we analyzed gene expression within the PpIX synthesis pathway to identify candidate molecules according to intraoperative 5-ALA-mediated fluorescence status. The most likely candidate gene was selected and confirmed by protein expression analysis. To evaluate the biological function of the molecule in PpIX synthesis, functional analysis was performed using specific, small interference (si)RNA in the SW-1783 human grade III glioma cell line. Results Among the genes involved in the porphyrin synthesis pathway, the mRNA expression of Peptide transporter 2 (PEPT2) in FGS fluorescence-positive gliomas was significantly higher than that in fluorescence-negative gliomas. Protein expression of PEPT2 was also significantly higher in the fluorescence-positive gliomas, which was confirmed by western blot analysis and immunofluorescence analysis. The siRNA-mediated downregulation of the mRNA and protein expression of PEPT2 led to decreased PpIX fluorescence intensity, as confirmed by fluorescence spectrum analysis. Conclusions The results suggest PEPT2 is an important candidate molecule in 5-ALA-mediated FGS in grade II/III gliomas. As the overexpression of PEPT2 was associated with higher PpIX fluorescence intensity, PEPT2 may improve fluorescence-guided resection in grade II/III gliomas.

Clinical diagnosis of attention-deficit/hyperactivity disorder in survivors of pediatric brain tumors Abstract Purpose Survivors of pediatric brain tumors often have neurodevelopmental late effects, such as inattention. Symptoms may mirror those of attention-deficit/hyperactivity disorder (ADHD), which affects ~ 5–8% of the general population. This retrospective study of survivors followed at a large tertiary care center examined the prevalence of a clinical diagnosis of ADHD, and risk factors associated with ADHD diagnosis and ADHD-related medication use. Methods A retrospective chart review of brain tumor survivors (n = 528), diagnosed between 2000 and 2015, who were at least 6 years old and 2 years from the end of tumor-directed therapy or from diagnosis, if no interventions were received. Clinical and demographic data were extracted from the medical record. Results Survivors were 55.7% male with mean age 8.15 ± 4.4 (0.0–16.0) years at brain tumor diagnosis. The most common diagnoses were low-grade glioma, medulloblastoma, and craniopharyngioma, with 52.5% of tumors supratentorial. Of the survivors, 81.3% received surgery, 40.0% radiation therapy, and 36.6% chemotherapy. Sixty-nine survivors (13.1%) had ADHD diagnoses, 105 (19.9%) had symptoms of ADHD without diagnoses, and 64 (12.1%) had ADHD medication use. ADHD diagnosis was associated with younger age at tumor diagnosis (p = 0.05) and supratentorial tumor location (p = 0.001). ADHD diagnosis was not associated with gender, tumor type, or treatment type. Conclusions Survivors of brain tumors are at increased risk of ADHD and related symptoms. The greatest increase in risk occurs for survivors with diagnoses at younger ages and supratentorial tumors. Additional research is warranted, as select survivors may benefit from behavioral or pharmacologic ADHD treatments to optimize functioning.

Combination anti-CXCR4 and anti-PD-1 immunotherapy provides survival benefit in glioblastoma through immune cell modulation of tumor microenvironment Abstract Background Emerging evidence suggests that myeloid cells play a critical role in glioblastoma (GBM) immunosuppression. Disappointing results of recent checkpoint inhibitor trials suggest that combination immunotherapy with alternative agents could be fruitful in overcoming immunosuppression. Overexpression of chemokine receptor CXCR4 is associated with poor prognosis in GBM. We investigate the treatment effects of combination immunotherapy with anti-PD-1 and anti-CXCR4 in a murine glioma model. Methods C57BL/6 mice were implanted with GL261-Luc+ glioma cells and randomized into 4 arms: (1) control (2) anti-PD-1 (3) anti-CXCR4, and (4) anti-PD-1 and anti-CXCR4 therapy. Overall survival and median survival were assessed. Cell populations were assessed by flow cytometry. Results Combination therapy conferred a significant survival benefit compared to control and monotherapy arms. Mice that received combination therapy demonstrated immune memory and decreased populations of immunosuppressive tumor-infiltrating leukocytes, such as monocytic myeloid-derived suppressor cells and microglia within the brain. Furthermore, combination therapy improved CD4+/CD8+ ratios in the brain as well as contributed to increased levels of pro-inflammatory cytokines. Conclusions Anti-CXCR4 and anti-PD-1 combination immunotherapy modulates tumor-infiltrating populations of the glioma microenvironment. Targeting myeloid cells with anti-CXCR4 facilitates anti-PD-1 to promote an antitumor immune response and improved survival rates.

Diagnostic delay and morbidity of central nervous system tumors in children and young adults: a pediatric hospital experience Abstract Introduction For children with central nervous system (CNS) tumors, survival rates remain significantly lower than other childhood malignancies with a substantial increase in disability of survivors. Given this, it is imperative that these children are identified at the earliest sign of symptom onset. Our institution aimed to identify diagnostic delays, morbidity and mortality, and specific barriers that may exist within our specific healthcare system that result in diagnostic delay. Methods A retrospective chart review was performed of newly diagnosed CNS tumors between January 1, 2008 and December 31, 2017. Results 235 patient cases were reviewed, 34 (14.5%) of which had an associated tumor predisposition syndrome. Median age at the time of diagnosis was 9 years (range 1 day to 25 years), with median number of days from symptom onset to definitive diagnosis of 42 days (interquartile range 14–120 days). Delays longer than 60 days occurred in 95 (47.5%) patients. The 10 year relative survival rate for all tumors was 86.8%. Conclusions Our institution had a shorter interval from symptom onset to diagnosis than currently reported in the literature, as well as a decrease in associated morbidity. In addition, for those with longer delays, we were able to characterize the etiology and barriers leading to these delays. With these identified, we are able to utilize this knowledge to further improve education and awareness in community members and healthcare professionals to continue to improve the time to diagnosis in the future.

A critical assessment of the quality of radiation therapy in Israel: time to initiation of treatment of spinal cord compression as an index of efficiency Abstract Introduction Radiotherapy departments function under workload pressure. We examined the process from referral to treatment initiation for spinal cord compression (SCC), one of the most daunting clinical scenarios in oncology. Methods We identified 235 patients with SCC, treated between 2013–2015. Two physicians classified cases as "emergent" or "urgent" (treatment within 24 or 72 h, respectively). Results The distribution of referrals over the week was uniform for inpatients. In contrast, there was a referral peak (62.27%) during the first two workdays for emergency ambulatory patients (p = 0.011). There were few weekend referrals in all groups (3.0%). There was a statistically shorter interval between referral and treatment for emergent versus urgent cases (0.94 days vs. 4.17 days; p < 0.0001, Bonferroni correction p < 0.0005). Conclusion Time elapsed between referral and treatment of SCC may constitute a quality index in neuro-oncology. Modern departments of radiotherapy should determine the degree to which they can successfully implement such treatment. Patients with cancer and their physicians should be taught to recognize signs of SCC to expedite intervention.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com