The role of intrapartum intravenous therapy and method of delivery on newborn weight loss : challenging the 7% rule

It is common practice to initiate supplemental feeding in newborns if body weight decreases by 7-10% in the first few days after birth (7-10% rule). Standard hospital procedure is to initiate intravenous therapy once a woman is admitted to give birth. However, little is known about the relationship between intrapartum intravenous therapy and the amount of weight loss in the newborn. The present research was undertaken in order to determine what factors contribute to weight loss in a newborn, and to examine the relationship between the practice of intravenous intrapartum therapy and the extent of weight loss post-birth. Using a cross-sectional design with a systematic random sample of 100 mother-baby dyads, we examined properties of delivery that have the potential to impact weight loss in the newborn, including method of delivery, parity, duration of labour, volume of intravenous therapy, feeding method, and birth attendant. This study indicated that the volume of intravenous therapy and method of delivery are significant predictors of weight loss in the newborn (R2=15.5, p<0.01). ROC curve analysis identified an intravenous volume cut-point of 1225 ml that would elicit a high measure of sensitivity (91.3%), and demonstrated significant Kappa agreement (p<0.01) with excess newborn weight loss. It was concluded that infusion of intravenous therapy and natural birth delivery are discriminant factors that influence excess weight loss in newborn infants. Acknowledgement of these factors should be considered in clinical practice.

Early detection and intervention for infants at risk of autism spectrum disorders

Autism is a developmental disorder that is characterized by abnonnal social interactions and communications as well as repetitive and restricted activities and interests. There is evidence of a genetic component, as 5% of younger siblings are diagnosed if their older sibling has been diagnosed. Autism is generally not diagnosed until age 3 at the earliest, yet it has been shown that early intervention for children with autism can greatly increase their functioning. Because of this, it is important that symptoms of autism are identified as early as possible so that diagnosis can occur as soon as possible to allow these children the earliest intervention. This thesis was divided into two parts. The first looked at the psychometrics of two proposed measures, the Parent Observation Checklist (POC), administered monthly, and the Infant Behavior Summary Evaluation (mSE), administered bimonthly, to see if they can be used with the infant population to identify autistic symptoms in infants who are at high risk for autism or related problems because they have an older sibling with autism. Study 1 reported acceptable psychometric properties of both the POC and IBSE in terms of test-retest reliability, internal consistency, construct validity and predictive validity. These results provide preliminary evidence that parent report measures can help to detect early symptoms of ASD in infants. The POC was shown to differentiate infants who were diagnosed from a matched group that was not diagnosed by 3 years of age. The second part of this thesis involved a telephone interview of parents who reported developmental and/or behavior problems in their high-risk infants that may be early signs of Autism Spectrum Disorder (ASD). During the interview, a service questionnaire was administered to see what interventions (including strategies recommended by the researchers) their at risk infants and affected older siblings were receiving, how satisfied the parents were with them and how effective they felt the interventions were. 3 Study 2 also yielded promising results. Parents utilized a variety of services for at risk infants and children with ASD. The interventions included empirically validated early intervention (e.g., ABA) to non-empirically validated treatments (e.g., diet therapy). The large number of nonempirically validated treatments parents used was surprising, yet parents reported being involved and satisfied, and thought that the services were effective. Parents' perceptions of their stress levels went down slightly and feelings of competence rose when they accessed services for their infants. Overall, the results of this thesis provide new evidence that parent-report methods hold promise as early detection instruments for ASD in at-risk infants. More research is needed to further validate these instruments as well as to understand the variables related to the parents' choice of early intervention for their at risk and affected children.

The influence of skeletal muscle cell volume on the regulation of carbohydrate uptake and muscle metabolism

This study investigated the regulation of carbohydrate metabolism and glucose uptake through changes in skeletal muscle cell volume. Using an established invitro isolated whole muscle model, soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected from male rats and incubated in an organ bath containing Sigma medium-199 with 8 mM D-glucose altered to target osmolality (hypo-osmotic: HYPO, iso-osmotic: ISO, hyper-osmotic: HYPER; 190, 290, 400 mmol/kg). Muscles were divided into two groups; metabolite (MM) and uptake (MU). MM (N=48) were incubated for 60 minutes and were then immediately flash frozen. MU (N=24) were incubated for 30 minutes and then the extracellular fluid was exchanged for media containing ^H-glucose and ^'*C-mannitol and incubated for another 30 minutes. After the incubation, the muscles were freeze clamped. Results demonstrated a relative water decrease and increase in HYPER and HYPO, respectively. EDL and SOL glucose uptakes were found to be significantly greater in HYPER conditions. The HYPER condition resulted in significant alterations in muscle metabolite concentrations (lower glycogen, elevated lactate, and G-6-P) suggesting a catabolic cell state, and an increase in glycogen synthase transformation when compared to the HYPO group. In conclusion, skeletal muscle cell volume alters rates of glucose uptake with further alterations in muscle metabolites and glycogen synthase transformation.

Lifespan, body size and oxygen : aerobic metabolism and oxidative stress in cultured fibroblasts /

The allometric scaling relationship observed between metabolic rate (MR) and species body mass can be partially explained by differences in cellular MR (Porter & Brand, 1995). Here, I studied cultured cell lines derived from ten mammalian species to determine whether cells propagated in an identical environment exhibited MR scaling. Oxidative and anaerobic metabolic parameters did not scale significantly with donor body mass in cultured cells, indicating the absence of an intrinsic MR setpoint. The rate of oxygen delivery has been proposed to limit cellular metabolic rates in larger organisms (West et al., 2002). As such cells were cultured under a variety of physiologically relevant oxygen tensions to investigate the effect of oxygen on cellular metabolic rates. Exposure to higher medium oxygen tensions resulted in increased metabolic rates in all cells. Higher MRs have the potential to produce more reactive oxygen species (ROS) which could cause genomic instability and thus reduced lifespan. Longer-lived species are more resistant to oxidative stress (Kapahi et al, 1999), which may be due to greater antioxidant and/or DNA repair capacities. This hypothesis was addressed by culturing primary dermal fibroblasts from eight mammalian species ranging in maximum lifespan from 5 to 120 years. Only the antioxidant manganese superoxide dismutases (MnSOD) positively scaled with species lifespan (p<0.01). Oxidative damage to DNA is primarily repaired by the base excision repair (BER) pathway. BER enzyme activities showed either no correlation or as in the case of polymerase p correlated, negatively with donor species (p<0.01 ). Typically, mammalian cells are cultured in a 20% O2 (atmospheric) environment, which is several-fold higher than cells experience in vivo. Therefore, the secondary aim of this study was to determine the effect of culturing mammalian cells at a more physiological oxygen tension (3%) on BER, and antioxidant, enzyme activities. Consistently, standard culture conditions induce higher antioxidant and DNA ba.se excision repair activities than are present under a more physiological oxygen concentration. Therefore, standard culture conditions are inappropriate for studies of oxidative stress-induced activities and species differences in fibroblast DNA BER repair capacities may represent differences in ability to respond to oxidative stress. An interesting outcome firom this study was that some inherent cellular properties are maintained in culture (i.e. stress responses) while others are not (i.e. MR).

The effect of extracellular osmolality on cell volume and resting skeletal muscle metabolism

The purpose of the current investigation was to establish an in-l'itro skeletal muscle model to study acute alterations in resting skeletal muscle cell volume. Isolated. whole muscle (SOL and EDL) was dissected from Long Evans rats and incubated for 60 min in Sigma Medium-199 (resting tension (lg). bubbled with 95:5% 02:C02, 30 ± 2°C, and pH 7.4). Media osmolality was altered to simulate hypo-osmotic (190 ± 10 Osm) (HYPO) or hyper-osmotic conditions (400 ± 10 Osm) (HYPER) while an iso-osmotic condition (290± 1 0 Osm) (CON) served as a control (n= 17.19.17). Following incubation, relative muscle water content decreased with HYPER and increased with HYPO in both muscle types (p<0.05). The cross-sectional area of HYPO SOL type I and type II fibres increased (p<0.05) while the EDL type 11 fibre area decreased in HYPER and increascd from HYPO exposure. Furthermore, HYPER exposure in both muscles lead to decreased ATP and phosphocreatine (p<0.05) and increased creatine and lactate (p<0.05) compared to CON. This isolated skeletal muscle model proved viable and demonstrated that altering extracellular osmolality could cause acutc alterations in muscle water content and resting muscle metabolism.

The influence of skeletal muscle cell volume on carbohydrate metabolism in contracting skeletal muscle

This study investigated the regulation of carbohydrate metabolism through changes in skeletal muscle cell volume immediately post contraction and during recovery. Using an established in vitro isolated muscle strip model, soleus (SOL) and extensor digitorum longus (EDL) were dissected from male rats and incubated in an organ bath (perfused with 95% O2; 5% CO2, pH 7.4, temperature 25°C) containing medium- 199 altered to a target osmotic condition (iso-, hypo- or hyper-osmotic; 290, 1 80, 400 mmol/kg). Muscles were stimulated for 10 minutes (40 Hz SOL; 30 Hz EDL) and then either immediately flash frozen or allowed to recover for 20 minutes before subsequent metabolite and enzyme analysis. Results demonstrated a relative water decrease in HYPER vs. HYPOosmotic condition (n=8/group; p<0.05) regardless of muscle type. Specifically, the SOL HYPER condition had elevated metabolite concentrations after 10 minutes of stimulation in comparison to both HYPO and ISO (p<0.05), while EDL muscle did not show any significant difTerences between the HYPER or HYPO conditions. After 20 minutes of recovery, metabolic changes occurred in both SOL and EDL with the SOL HYPER condition showing greater relative changes in metabolite concentrations versus HYPO. The results of the current study have demonstrated that osmotic imbalance induces metabolic change within the skeletal muscle cell and muscle type may influence the mechanisms utilized for cell volume regulation.

An investigation into fungal metabolism of halogenated and related steroids

Fungal metabolism of halogenated and related steroids was investigated. The fungi Aspergillus niger ATCC 9142, Curvularia lunata NRRL 2380 and Rhizopus stolonifer ATCC6227b were studied in this regard. 2l-Fluoro-, 2l-chloro, 2l-bromo- and 2l-methyl-pregn-4-ene-3,20diones were prepared and incubated with ~ niger (a C-2l-hydroxylator) in order to observe the effect of the C-2l substituent on the metabolism of these substrates. In all four cases, the C-2l substituent prevented any significant metabolism of these substrates. llB-Fluoropregn-4-ene-3,20-dione was prepared and incubated with C. lunata (an llB-hydroxylator) and ~ stolonifer (an lla-hydroxylator). With ~ lunata, the ll-fluoro- substituent prevent hydroxylation at the 11 position, but diverted it to a site remote from the fluorine atom. In contrast, with ~ stolonifer the llB-fluoro- substituent, although slowing the apparent rate of hydroxylation, did not prevent its occurrence at the 11a- position. llB-Hydroxypregn-4-ene-3,20-dione was also incubated with R. stolonifer. The llB-hydroxy-;group did not appear to have any significant effect on hydroxylation at the lla- position. The incubation of a substrate, unsaturated at a favoured site of hydroxylation with Rhizopus arrhizus ATCC 11145 provided a complex mixture of products; among them were both the a and S epoxides. The formation of these products is rationalized as arising because of the lack of regio- and stereospecificity of the hydroxylase enzyme(s) involved.

The influence of carbon dioxide on growth and metabolism of etiolated Avena sativa 1 coleoptiles

The influence of carbon dioxide on growth and protein synthesis of etiolated Avena coleoptiles was investigated. Evidence is presented that 0.03% carbon dioxide stimulated both these processes; and that carbon dioxide stimulated growth depends on carbon dioxide stimulated protein synthesis, In addition the evidence indicates that carbon dioxide stimulated growth is mediated by metabolism, and that carbon dioxide stimulates growth through a dark fixation process. Growth studies also demonstrated that IAA and carbon dioxide stimulated growth in a synergistic manner.

Using the Reliable Change Index Statistic to Analyze Developmental Changes in Infants at Risk for Autism Spectrum Disorder

Longitudinal studies of the development of autism spectrum disorders (ASD) provide an understanding of which variables may be important predictors of an ASD. The objective of the current study is to apply the reliable change index (RCI) statistic to examine whether the Parent Observation of Early Markers Scale (POEMS) is sensitive to developmental change, and whether these changes can be quantified along a child’s developmental trajectory. Ninety-six children with older siblings with autism were followed from 1-36 months of age. Group-based RCI analysis confirms that the POEMS is capable of detecting significant changes within pre-defined diagnostic groups. Within-subject analysis suggests that ongoing monitoring of a child at-risk for an ASD requires interpretation of both significant intervals identified by the RCI statistic, as well as the presence of repeated high (i.e., >70) scores. This study provides preliminary evidence for a reasonably sensitive and specific means by which individual change can be clinically monitored via parent report.

Synthesis of cytochrome P450 inhibitors of vitamin E metabolism

Please consult the paper edition of this thesis to read. It is available on the 5th Floor of the Library at Call Number: Z 9999 C54 O46 2007

Comparison of the Behavioural Development of Infants at Low and High-Risk for Autism Spectrum Disorders

By identifying early signs of Autism Spectrum Disorder, early intervention or parent training could be implemented and assist in increasing the developmental trajectory for these infants. This cross sectional study used the Parent Observation of Early Markers Scale (POEMS) to identify early signs of ASD in 69 high-risk (older sibling diagnosed with ASD) and 69 matched low-risk infants' families (no family history of ASD) between 6 and 36 months of age. The preliminary results showed the high-risk children had significantly more elevated POEMS items than the low-risk children at 12, 18,24,30 and 36 months of age. The results suggest that at-risk infants may show signs of ASD as early as 12 months of age, and that the POEMS could be used to guide early intervention or parent training for children 12 months or older.

Cellular Mechanisms of Resveratrol's Interaction with Mitochondrial Reactive Oxygen Species Metabolism

Resveratrol, a polyphenol found naturally in red wines, has attracted great interest in both the scientific community and the general public for its reported ability to protect against many of the diseases facing Western society today. While the purported health effects of resveratrol are well characterized, details of the cellular mechanisms that give rise to these observations are unclear. Here, the mitochondrial antioxidant enzyme Mn superoxide dismutase (MnSOD) was identified as a proximal target of resveratrol in vitro and in vivo. MnSOD protein and activity levels increase significantly in cultured cells treated with resveratrol, and in the brain tissue of mice given resveratrol in a high fat diet. Preventing the increase in MnSOD levels eliminates two of resveratrol’s more interesting effects in the context of human health: inhibition of proliferative cell growth and cytoprotection. Thus, the induction of MnSOD is a critical step in the molecular mechanism of resveratrol. Mitochondrial morphology is a malleable property that is capable of impeding cell cycle progression and conferring resistance against stress induced cell death. Using confocal microscopy and a novel ‘cell free’ fusion assay it was determined that concurrent with changes in MnSOD protein levels, resveratrol treatment leads to a more fused mitochondrial reticulum. This observation may be important to resveratrol’s ability to slow proliferative cell growth and confer cytoprotection. Resveratrol's biological activities, including the ability to increase MnSOD levels, are strikingly similar to what is observed with estrogen treatment. Resveratrol fails to increase MnSOD levels, slow proliferative cell growth and confer cytoprotection in the presence of an estrogen receptor antagonist. Resveratrol's effects can be replicated with the specific estrogen receptor beta agonist diarylpropionitrile, and are absent in myoblasts lacking estrogen receptor beta. Four compounds that are structurally similar to resveratrol and seven phytoestrogens predicted to bind to estrogen receptor beta were screened for their effects on MnSOD, proliferative growth rates and stress resistance in cultured mammalian cells. Several of these compounds were able to mimic the effects of resveratrol on MnSOD levels, proliferative cell growth and stress resistance in vitro. Thus, I hypothesize that resveratrol interacts with estrogen receptor beta to induce the upregulation of MnSOD, which in turn affects cell cycle progression and stress resistance. These results have important implications for the understanding of RES’s biological activities and potential applications to human health.

A Phenomenological Study Exploring the Experiences of Men Who Work in Maternal-Newborn Nursing Positions

The aim of this study was to explore the experiences of men who choose to work in maternal-newborn nursing roles. Using a qualitative phenomenological approach, interviews were conducted with a purposeful sample of six male nurses who worked in maternal-newborn settings using a semi-structured guide. Four themes emerged: Motivation and Influences in Career Choice, Barriers to Developing Caring Confidence as Maternal-Newborn Nurses, Surviving as Men in Maternal-Newborn Nursing, and The Invisible Norms Associated with Men in Maternal-Newborn Nursing. The study generated meaning surrounding career selection and addressed motivating factors such as role modeling, life experience, and passion for the area of specialization or convenience. There is importance in understanding the experiences of men who choose to work in maternal-newborn nursing roles. Thus, this research has implications for nursing, practice, education, and research, particularly with nursing leadership, policy makers, educators, guidance counselors, and men considering maternal-newborn nursing roles.

Parent Prediction of Autism Spectrum Disorder in Infants At Risk: A Follow-up Study

Later-born siblings of children with autism spectrum disorder (ASD) are considered at biological risk for ASD and the broader autism phenotype. Early screening may detect early signs of ASD and facilitate intervention as soon as possible. This follow-up study revisits and re-examines a second-degree autism screener for children at biological risk of autism, the Parent Observation Early Markers Scale (POEMS, Feldman et al., 2012). Using available follow-up information, 110 children (the original 108 infants plus 2 infants recruited after the completion of the original study) were divided into three groups: diagnosed group (n = 13), lost diagnosis group (n = 5), and undiagnosed group (n = 92). The POEMS continued to show acceptable predictive validity. The POEMS total scores and mean number of elevated items were significantly higher in the diagnosed group than the undiagnosed group. The lost diagnosis group did not differ from the undiagnosed group on POEMS total scores and elevated items at any age, but the lost diagnosis group had significantly lower total scores and number of elevated items than the diagnosed group starting at 18 months. Both ASD core and subsidiary behaviours differentiated the diagnosed and undiagnosed groups from 9−36 months of age. Using 70 as a cut-off score, sensitivity, specificity, and positive predictive value (PPV) were .69, .84, and .38, respectively. The study provides further evidence that the POEMS may serve as a low-cost early screener for ASD in at risk children and pinpoint specific developmental and behavioural problems that may be amenable to very early intervention.