Grace College & Seminary

In 2011, Lake Erie experienced the largest harmful algal bloom in its recorded history, with a peak intensity over three times greater than any previously observed bloom. Here we show that long-term trends in agricultural practices are consistent with increasing phosphorus loading to the western basin of the lake, and that these trends, coupled with meteorological conditions in spring 2011, produced record-breaking nutrient loads. An extended period of weak lake circulation then led to abnormally long residence times that incubated the bloom, and warm and quiescent conditions after bloom onset allowed algae to remain near the top of the water column and prevented flushing of nutrients from the system. We further find that all of these factors are consistent with expected future conditions. If a scientifically guided management plan to mitigate these impacts is not implemented, we can therefore expect this bloom to be a harbinger of future blooms in Lake Erie.

Relieving phosphorus loading is a key management tool for controlling Lake Erie eutrophication. During the 1960s and 1970s, increased phosphorus inputs degraded water quality and reduced central basin hypolimnetic oxygen levels which, in turn, eliminated thermal habitat vital to cold-water organisms and contributed to the extirpation of important benthic macroinvertebrate prey species for fishes. In response to load reductions initiated in 1972, Lake Erie responded quickly with reduced water-column phosphorus concentrations, phytoplankton biomass, and bottom-water hypoxia (dissolved oxygen < 2 mg/l). Since the mid-1990s, cyanobacteria blooms increased and extensive hypoxia and benthic algae returned. We synthesize recent research leading to guidance for addressing this re-eutrophication, with particular emphasis on central basin hypoxia. We document recent trends in key eutrophication-related properties, assess their likely ecological impacts, and develop load response curves to guide revised hypoxia-based loading targets called for in the 2012 Great Lakes Water Quality Agreement. Reducing central basin hypoxic area to levels observed in the early 1990s (ca. 2000 km2) requires cutting total phosphorus loads by 46% from the 2003–2011 average or reducing dissolved reactive phosphorus loads by 78% from the 2005–2011 average. Reductions to these levels are also protective of fish habitat. We provide potential approaches for achieving those new loading targets, and suggest that recent load reduction recommendations focused on western basin cyanobacteria blooms may not be sufficient to reduce central basin hypoxia to 2000 km2.

Objectives Considerable progress has been made in the treatment of Alzheimer's disease (AD), but all available strategies focus on alleviating symptoms rather than curing, which means that AD is viewed as an unresolvable neurodegenerative disease. Nanotechnological applications offer an alternative platform for the treatment of neurodegenerative diseases. This review aims to summarize the recent nanomedicine and nanotechnology developments for the treatment of AD. Key findings A plethora of nanocarriers and nanoparticle prodrugs have been reported to have negligible cytotoxicity in animal models, and these developments have revealed new opportunities for development of new classes of potent drug formulations for AD. Different nanotechnology-based approaches such as polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes and metal-based carriers have been developed over the past decade, and they have been focusing on both neuroprotective and neurogenerative techniques to treat AD. Studies also reveal that nanotechnological approaches can aid in early diagnosis of AD and enhance therapeutic efficacy and bioavailability. Summary Notably, the drugs used conventionally to target the central nervous system have limitations that include an inability to cross the 'blood-brain barrier' or the 'blood-cerebrospinal fluid barrier' effectively and high drug efflux due to the activity of P-glycoprotein, but these limitations can be successfully overcome when nanocarriers are used for targeted drug delivery in AD.

OBJECTIVES: Withania somnifera has been in use for several thousand years in Ayurveda to treat various neurological disorders. There is, however, not much scientific data on its protective role in neuronal pathology specifically against brain oxidative stress. Hence, an attempt is made in this work for systematic review and meta-analysis of W. somnifera on neurobehavioural disorders induced by brain oxidative stress in rodents. METHODS: A systematic search of the effect of W. somnifera on brain oxidative stress-induced neuronal pathology was performed using electronic databases. The systematic review was performed on neurobehavioural parameters, whereas meta-analysis of W. somnifera effect was done on oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione and lipid peroxidation), nitrite, protein carbonyl, AchE, ChAT and Ach of rodent brain. Data were analysed using Review Manager Software. KEY FINDINGS: Twenty-eight studies were selected based upon the inclusion and exclusion criteria. W. somnifera appreciably inhibited the neurological abnormalities due to oxidative stress in rodent brain produced by different physical and chemical stimuli. W. somnifera also significantly restored the altered oxidative and other stress markers in different parts of rodent brain. SUMMARY: The systematic review provides scientific evidence for the traditional claim of W. somnifera use in different neurological aliments. However, future clinical trials are mandated to establish the therapeutic efficacy and safety in human beings.

A series of (2E)-1-(5-bromothiophen-2-yl)-3-(para-substituted phenyl)prop-2-en-1-ones (TB1-TB11) was synthesized and tested for inhibitory activity toward human monoamine oxidase (hMAO). All compounds were found to be competitive, selective, and reversible toward hMAO-B except (2E)-1-(5-bromothiophen-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one (TB7) and (2E)-1-(5-bromothiophen-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one (TB8), which were selective inhibitors of hMAO-A. The most potent compound, (2E)-1-(5-bromothiophen-2-yl)-3-[4-(dimethylamino)phenyl]prop-2-en-1-one (TB5), showed the best inhibitory activity and higher selectivity toward hMAO-B, with Ki and SI values of 0.11±0.01 μm and 13.18, respectively. PAMPA assays for all compounds were carried out in order to evaluate the capacity of the compounds to cross the blood-brain barrier. Moreover, the most potent MAO-B inhibitor, TB5, was found to be nontoxic at 5 and 25 μm, with 95.75 and 84.59 % viability among cells, respectively. Molecular docking simulations were carried out to understand the crucial interactions responsible for selectivity and potency.

This study aims at understanding the impacts of projected climate change on the hydrological processes within the Maumee River watershed (16 395 km 2 ) lying in the Lake Erie Basin using soil and water assessment tool (SWAT). The model was calibrated and validated for a baseline time‐period of 1995–2005. Downscaled ensemble projected temperature and precipitation data from three general circulation models (GCMs) was then used to assess future flow, sediment, and nutrient loading in the watershed for mid‐century (2045–2055) and late‐century (2089–2099) time periods. Compared to the baseline, a 2.9°C rise in the annual average temperature along with a 3.2% fall in the annual precipitation in the mid‐century time‐period is projected to reduce annual flow volumes, and suspended solids (SS), total phosphorus (TP), nitrate (NO 3 ) loads by 8.5, 10.4, 8.5, and 9.9%, respectively. Similarly, for the late‐century a 4.3°C rise in the annual average temperature along with a 5.6% rise in the annual precipitation is projected to increase annual flow volumes, and SS, TP, NO 3 loads by 9.7, 19.6, 3.5, and 6.8%, respectively. Temporal shifts in climatic conditions were also projected for both the future time‐periods with higher temperatures throughout the year along with wetter winters and drier summers. Implications of these changes would include the need for an increased focus on pollutant loadings for total maximum daily load guidelines and possible lengthening of crop growing cycles.

Widespread adoption of agricultural conservation measures in Lake Erie's Maumee River watershed may be required to reduce phosphorus loading that drives harmful algal blooms and hypoxia. We engaged agricultural and conservation stakeholders through a survey and workshops to determine which conservation practices to evaluate. We investigated feasible and desirable conservation practices using the Soil and Water Assessment Tool calibrated for streamflow, sediment, and nutrient loading near the Maumee River outlet. We found subsurface placement of phosphorus applications to be the individual practice most influential on March-July dissolved reactive phosphorus (DRP) loading from row croplands. Perennial cover crops and vegetated filter strips were most effective for reducing seasonal total phosphorus (TP) loading. We found that practices effective for reducing TP and DRP load were not always mutually beneficial, culminating in trade-offs among multiple Lake Erie phosphorus management goals. Adoption of practices at levels considered feasible to stakeholders led to nearly reaching TP targets for western Lake Erie on average years; however, adoption of practices at a rate that goes beyond what is currently considered feasible will likely be required to reach the DRP target.

INTRODUCTION: Chalcones are one of the major classes of naturally occurring compounds and have a vast significance in medicinal chemistry, presenting with a wide scope of pharmacological actions. DISCUSSION: The present review focused our attention onto the monoamine oxidase inhibitory activity of natural and synthetic chalcones. The review also emphasises the structure-activity relationship studies and molecular recognition of chalcones towards MAO-A and B inhibition. CONCLUSION: Many of the studies clearly revealed that most of the chalcones showed selective, reversible and potent MAO-B inhibition compared to MAO-A. Recent studies also showed that heteroaryl-based chalcones are potent MAO-A inhibitors.

Abstract Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase‐B (MAO‐B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO‐B (hMAO‐B) inhibitors, two series of twenty chalcones containing electron‐donating and electron‐withdrawing substituents were synthesized. All compounds were found to be competitive, selective, and reversible inhibitors of hMAO‐B except (2 E )‐1‐(4‐methylphenyl)‐3‐(4‐nitrophenyl)prop‐2‐en‐1‐one ( P7 ) and (2 E )‐1‐(4‐chlorophenyl)‐3‐(4‐nitrophenyl)prop‐2‐en‐1‐one ( P17 ), which were found to be selective inhibitors of hMAO‐A. The most potent hMAO‐B inhibitor, (2 E )‐1‐(4‐chlorophenyl)‐3‐(4‐ethylphenyl)prop‐2‐en‐1‐one ( P16 ), showed a K i value of 0.11±0.01 μ m . Molecular docking simulations were carried out to identify the hypothetical binding mode for the most potent compounds in the active sites of hMAO‐A and B. The ability of the compounds to cross the blood–brain barrier was assessed by parallel artificial membrane permeability assay (PAMPA). Additionally, the most potent hMAO‐B inhibitor P16 showed no toxicity in cultured hepatic cells at concentrations of 5 and 25 μ m .

The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs (1–9) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1–9, highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.

In the five membered nitrogen containing heterocyclic family, pyrazoline could be recognized as a promising scaffold for the inhibition of Monoamine oxidase. Substitution at 1, 3 and 5-position of the pyrazoline nucleus displayed a significant activity towards MAO in the past 15 years. Our study identified the detailed structure activity relationship, the structural requirement for enzyme interaction and the effect of chirality on the pyrazoline nucleus towards MAO-A and MAO-B. We propose that the selectivity of pyrazoline nucleus towards MAO isoenzyme depends up on the bulkiness of the ring in the 1 and 3 position of the scaffold. The current review revealed that the derivatives of pyrazolines have proven to be versatile pharmacophores for the inhibition of MAO on the basis of existing literatures between (1998-2013).

values of 35.35 ± 0.47, 15.61 ± 0.057 and 26.61 ± 0.338 μM, respectively. Blood-brain barrier (BBB) permeation was studied using the parallel artificial membrane permeation assay (PAMPA) method. Molecular docking studies were carried out using AutoDock 4.2.

The synthesis of some novel (1-H) benzimidazole bearing pyrimidine-trione based MAO-A inhibitors were achieved by the reaction between 2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-ones(4a–f) and barbituric acid in the presence of a catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1HNMR and mass spectra analyses. All the synthesized derivatives showed good antidepressant activity when compared to the standard clomipiramine at a dose level of 20 mg/kg. The compound (5d) 5-{(2E)-1-(1H-benzimidazol-2-yl)-3-[4-(dimethylamino)phenyl] prop-2-en-1-ylidene} pyrimidine-2, 4, 6(1H,3H,5H)-trione significantly reduced the duration of immobility times at 50 mg/kg−1 dose level when compared to the standard drug. Molecular docking studies revealed the need for an extra hydrophobic interaction in the titled scaffold for acquiring the promising experimental values. It has been concluded that the computational values obtained after the docking calculation are in good agreement with the experimental values.

The high prevalence of co-occurring mental health and substance use disorders in young people is well established. Despite this, there are low rates of detection of co-occurring disorders across alcohol and other drug (AOD) services within Australia. This paper describes the development, implementation and evaluation of a mental health screening tool and training programme within the youth AOD sector. Thirty youth AOD workers received training in mental health screening, and the screening tool was subsequently piloted on 84 young people accessing two youth AOD services. Training was evaluated using measures of the trainee's mental health knowledge, attitudes, skills and confidence in mental health screening at baseline and 12-month follow-up. Feedback from young people supported the feasibility, acceptability and relevance of the screening tool. Evaluation of the associated training programme indicated improvements in AOD workers' mental health knowledge, skills and confidence in mental health screening. These findings provide preliminary evidence of the feasibility and acceptability of the mental health screening tool to young people and the effectiveness of the training package within the youth AOD sector.

Abstract The design of selective, reversible and non‐toxic hMAO−B inhibitors has received increasing attention due to their perceived utility in targeting of neurological disorders like Alzheimer's and Parkinson's diseases. For this purpose, herein, we report the inhibitory studies on monoamine oxidase of a series of ( 2E )‐1‐(2, 5‐dichlorothiophen‐3‐yl)‐3‐(4‐substitutedphenyl) prop‐2‐en‐1‐ones ( S1 ‐ S9 ). All the compounds were found to be competitive, selective, and reversible inhibitors of hMAO−B except (2 E )‐1‐(2, 4‐dichlorothiophen‐3‐yl)‐3‐(4‐nitrophenyl) prop‐2‐en‐1‐one ( S6 ) which is found to be non‐selective MAO inhibitor. The potent hMAO−B inhibitor, (2 E )‐1‐(2, 4‐dichlorothiophen‐3‐yl)‐3‐[4‐(dimethylamino) phenyl] prop‐2‐en‐1‐one ( S4 ), showed a Ki value of 0.041 μM better than the standard drug, selegiline (hMAO−B with Ki = 0.302 μM). Moreover, S4 , was nontoxic in cultured hepatic cells at 5 and 25 μM, with 94.44 and 88.00% viable cells, respectively. Molecular docking and molecular dynamics simulation studies were carried out using Autodock‐vina and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO−B inhibitor, S4 .

Over the past decade, a contentious debate regarding delayed memories of childhood sexual abuse (CSA) has existed. In order to address this debate, 240 female participants completed questions about CSA, the Dissociative Experience Scale (Bernstein & Putnam, 1986), Perceived Emotional Closeness with Perpetrator Scale (Schultz, Passmore, & Yoder, 2000), and the Gudjonsson Suggestibility Scale 2 (GSS 2) (Gudjonsson, 1987). Eighty-two (36%) reported CSA and 37% of these indicated memory disturbances for the CSA. Participants reporting memory disturbances also reported significantly higher numbers of perpetrators, chemical abuse in their families, and closer relationships with the perpetrator(s) than participants reporting no memory disturbances. Implications for clinicians working with clients reporting CSA are discussed.

Richards, R. Peter, Ibrahim Alameddine, J. David Allan, David B. Baker, Nathan S. Bosch, Remegio Confesor, Joseph V. DePinto, David M. Dolan, Jeffrey M. Reutter, and Donald Scavia, 2012. Discussion –“Nutrient Inputs to the Laurentian Great Lakes by Source and Watershed Estimated Using SPARROW Watershed Models” by Dale M. Robertson and David A. Saad. Journal of the American Water Resources Association (JAWRA) 1‐10. DOI: 10.1111/jawr.12006 Abstract: Results from the Upper Midwest Major River Basin (MRB3) SPARROW model and underlying Fluxmaster load estimates were compared with detailed data available in the Lake Erie and Ohio River watersheds. Fluxmaster and SPARROW estimates of tributary loads tend to be biased low for total phosphorus and high for total nitrogen. These and other limitations of the application led to an overestimation of the relative contribution of point sources vs. nonpoint sources of phosphorus to eutrophication conditions in Lake Erie, when compared with direct estimates for data‐rich Ohio tributaries. These limitations include the use of a decade‐old reference point (2002), lack of modeling of dissolved phosphorus, lack of inclusion of inputs from the Canadian Lake Erie watersheds and from Lake Huron, and the choice to summarize results for the entire United States Lake Erie watershed, as opposed to the key Western and Central Basin watersheds that drive Lake Erie’s eutrophication processes. Although the MRB3 SPARROW model helps to meet a critical need by modeling unmonitored watersheds and ranking rivers by their estimated relative contributions, we recommend caution in use of the MRB3 SPARRROW model for Lake Erie management, and argue that the management of agricultural nonpoint sources should continue to be the primary focus for the Western and Central Basins of Lake Erie.

An exploratory investigation was conducted which indicated that students perceive certain types of criticism to be significantly more helpful than other types. The findings also indicated that perceptions of helpfulness are related to student levels of speech anxiety and student and instructor sex differences. These results provide implications for the refinement of instructor critique behavior.

Given the myriad positive effects of job satisfaction, analyzing its determinants continues to be a much-examined topic in public administration. Research on religiosity in the public sector suggests that faith is uniquely important among bureaucrats. However, the direct effect of religiosity on public employee job outcomes remains unexamined. This study brings together these fields to examine the role that religiosity plays in job satisfaction among public servants. Using a framework that integrates religion into the public sector workplace, I hypothesize that religiosity will have a positive effect on job satisfaction. Drawing on data from the General Social Survey from 2000 to 2016 and through the estimation of an ordered logit model, the findings from this study support this hypothesis. Ultimately, this study demonstrates that religiosity has a direct impact in the public sector workplace. This finding has numerous implications for public mangers—ranging from management practice to service delivery.

The present study was undertaken to establish the diuretic activity of ethanol and aqueous extract of dried leaves of Garcinia cambogia in rats. Aqueous and ethanol extracts of leaves were administered to experimental rats orally at doses of 100 and 200 mg/kg and compared with furosemide (20 mg/kg, intraperitoneally) as the standard. The parameters measured for diuretic activity were total urine volume, urine concentration electrolytes such as sodium, potassium and chloride have been evaluated . The rats treated with ethanol extract of Garcinia cambogia and aqueous extract of Garcinia cambogia in a dose of 100 and 200 mg/kg showed higher urine output when compared to the respective control. Both ethanol and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group.