Microbial Abundance and the Pattern of Escherichia coli Antibiotic Sensitivity and Resistance in Deer Creek and the Potential Impact of a Veterinarian Hospital’s Input

The gram-negative bacteria, E. coli, is an indicator of fecal input for both point and non-point source origin. The veterinarian hospital located on Deer Creek may contribute to high antibiotic levels, which are known to select for resistant strains of bacteria living in impacted waters. The water running north of the veterinarian hospital was considered potentially antibiotic influenced as it was downstream of the site. The origin of the stream and sites upstream from the hospital were considered influent water. Sediments were also collected from these sites to determine if more long term resident E. coli were present with elevated antibiotic resistance in stretches of the creek influenced by potential fecal input from the Veterinary Hospital. The antibiotics used in the experiment were chosen as they are specific to E. coli which are often associated with mammalian gut pathogens. The antibiotics; penicillin, tetracycline, gentamicin, amoxicillin, streptomycin and amoxicillin-clavulanate were tested using the Kirby Bauer method. The most extreme antibiotic sensitivity and resistance was present within water collected from the veterinarian hospital site. In water samples, the largest yield of bacteria were present at the site downstream from the hospital, indicating a potential impact on E. coli isolates antibiotic sensitivity/resistance patterns. Sediments from a neighborhood along the creek upstream of the Hospital contained the greatest amount of E. coli and other coliform bacteria. This indicated other potential sources of contamination could include homes and their septic systems in that part of the creek. Future studies will focus on these sites

Evaluating the Neuropsychological Presentation of Traumatic Brain Injuries

This Neurobehavioral Capstone focused on traumatic brain injury (TBI), which is one of the leading causes of death and disability in the United States for children and young adults. TBI refers to a disruption of the brain’s normal functioning as a result of an acute external force. The most common causes for a TBI include falls, vehicular accidents, struck by or against an object, and assaults. The incidence for each cause of a TBI changes with respect to age. Severity of a TBI is determined using the Glasgow Coma Scale, which monitors the patient’s eye movements, verbal response and motor response. Neuropsychological testing assesses the patient’s physical, cognitive, and behavioral deficits. These deficits include, but are not limited to, memory, processing speed, speech, executive function, and decision making. Results of neuropsychological testing help set a course for treatment and monitors the patient’s recovery. This treatment course may include physical therapy, cognitive therapy, speech therapy, occupational therapy, and psychological counseling. Observations at Bancroft NeuroRehab included the observation of neuropsychological testing of patients with TBIs and how their deficits helped direct their individualized treatment. The neuropsychological testing results also helped localize the specific areas in the brain affect by the acute injury for each patient. These observations will be discussed in light of the Neurobehavioral research in the area of TBI

Hematological monitoring during therapy with carbamazepine in children

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50302/1/410130622_ftp.pd

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms and here, we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure / function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era

Risk factors for youth violence: Youth violence commission, International Society For Research On Aggression (ISRA)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144599/1/ab21766.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144599/2/ab21766_am.pd

Negative parental responses to coming out and family functioning in a sample of lesbian and gay young adults

Parental responses to youths' coming out (CO) are crucial to the subsequent adjustment of children and family. The present study investigated the negative parental reaction to the disclosure of same-sex attraction and the differences between maternal and paternal responses, as reported by their homosexual daughters and sons. Participants' perceptions of their parents' reactions (evaluated through the Perceived Parental Reactions Scale, PPRS), age at coming out, gender, parental political orientation, and religiosity involvement, the family functioning (assessed through the Family Adaptability and Cohesion Evaluation Scales, FACES IV), were assessed in 164 Italian gay and lesbian young adults. Pearson correlation coefficients were calculated to assess the relation between family functioning and parental reaction to CO. The paired sample t-test was used to compare mothers and fathers' scores on the PPRS. Hierarchical multiple regression was conducted to analyze the relevance of each variable. No differences were found between mothers and fathers in their reaction to the disclosure. The analysis showed that a negative reaction to coming out was predicted by parents' right-wing political conservatism, strong religious beliefs, and higher scores in the scales Rigid and Enmeshed. Findings confirm that a negative parental reaction is the result of poor family resources to face a stressful situation and a strong belief in traditional values. These results have important implications in both clinical and social fields

Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease

Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t-tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD +/- 8.5) years versus 54.8 (SD +/- 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-epsilon 4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline (P = 0.006) and 46.1% versus 25.4% at last visit (P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency (P < 0.001), Trail Making Test Part B (P < 0.001) and digit span (P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points (P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD +/- 39.3) pg/ml dominantly inherited versus 296 (SD +/- 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels (P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles;sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia

Introduction: Structural brain imaging is paramount for the diagnosis of behavioural variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. Methods: A total of 515 subjects from two different bvFTD cohorts (training and independent validation cohorts) were used to perform voxel-wise morphometric analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from deformation-based morphometry differences in isolation and together with semantic fluency. Tenfold cross validation was used to assess the performance of the classifier within the training cohort. A second held-out cohort of genetically confirmed bvFTD cases was used for additional validation. Results: Average 10-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In the separate validation cohort of definite bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added semantic fluency scores. Conclusion: Our results show that structural MRI and semantic fluency can accurately predict bvFTD at the individual subject level within a completely independent validation cohort coming from a different and independent database