Expression of Pancreatitis-Associated Protein after Traumatic Brain Injury: A Mechanism Potentially Contributing to Neuroprotection in Human Brain

Neuronal cell death after severe traumatic brain injury (TBI) is caused by a complex interplay of pathological mechanisms including excitotoxicity, oxidative stress, mitochondrial dysfunction, extensive neuroinflammation, and ischemia-reperfusion injury. Pancreatitis-associated protein I (PAP I/reg2) was reported to be a survival factor for peripheral neurons, particularly sensory and motor neurons. In rat brains, by experimental TBI as well as by kainic acid induced brain seizure, PAP I and PAP III were found to be up-regulated in central neurons. In this study, we performed immunohistochemical staining in postmortem human brain from patients who died after severe TBI to demonstrate PAP expression on protein level in cerebellar Purkinje cells, pyramidal and granular neurons in cerebral cortex, and cortical neurons in the fore- and mid-brain. In primary cultures of rat brain cortical, hippocampal, and cerebellar neurons, we found neuroprotective effects for PAP I on H2O2-induced oxidative stress. Moreover, serum K+-deprivation induces apoptotic cell death in 55% of cerebellar granule neurons (CGN), whereas upon treatment with PAP I only 32% of CGN are apoptotic. Using Western blot analyses, we compared protein phosphorylation in neuronal signaling pathways activated by PAP I versus Interleukin-6 (IL-6). We found a rapid activation of Akt-kinase phosphorylation by PAP I with a peak at 15min, whereas IL-6 induces Akt-phosphorylation lasting longer than 30min. Phosphorylation of MAP-42/44 kinases is stimulated in a comparable fashion. Both, IL-6 and PAP I increase phosphorylation of NFκB for activation of gene transcription, whereas only IL-6 recruits STAT3 phosphorylation, indicating that STAT3 is not a target of PAP I transcription activation in brain neurons. Application of the Akt-inhibitor Wortmanin reveals only a partial inhibition of PAP I-dependent protection of CGN from H2O2-induced oxidative stress. Based on our findings, we suggest that PAP I is a long lasting neurotrophic signal for central neurons. The neuroprotective effects parallel those that have been described for effects of PAP I in ciliary neurotrophic factor (CNTF)-mediated survival of sensory and motor neurons. PAP I may act in autocrine and/or paracrine fashion and thus may contribute to endogenous protective mechanisms relevant under harmful conditions like oxidative stress, brain injury, or neurodegeneratio

Dietary management practices for type 1 diabetes mellitus by dietitians in KwaZulu-Natal

Background: In South Africa, 5% – 15% of diabetics have type 1 diabetes mellitus (T1DM). Dietitians are an important part of the diabetes management team; however, there is a lack of published data on the dietary management practices for T1DM by dietitians. Aim: The aim of this study was to determine the dietary management practices for T1DM by dietitians in KwaZulu-Natal (KZN). Setting: This study was conducted in KZN. Methods: A cross-sectional, descriptive study was conducted using a self-administered electronic questionnaire. Results: Of the 69 dietitians who participated, 58% (n = 40) used the American Diabetes Association (ADA) guidelines to manage T1DM; just under 35% (n = 24) spent over an hour with new cases; and 87% (n = 60) used face-to-face consultations for follow-up. Dietitians used the glycaemic index, portion control using the healthy eating plate, carbohydrate counting using nutritional labels and household measures and carbohydrate awareness to manage T1DM (p < 0.05). Dietitians also used the healthy eating plate (71%; n = 49) (p < 0.05) and household measures (73.9%; n = 51) (p < 0.05) to manage T1DM. Time constraints, the literacy level of the patient, available resources and language barriers all played a role in determining the dietary management practices used (p < 0.05). Conclusion: Most dietitians in KZN used the ADA dietary guidelines to manage T1DM, which highlights the need for South African dietary guidelines for the management of T1DM. Dietitians used a variety of different dietary methods to manage T1DM in practice. This suggests that dietitians are flexible in how they manage T1DM with no one particular method being used. A variety of factors also influenced which dietary management practices were chosen

Practices and perceptions of registered dietitians regarding the use of carbohydrate counting and barriers associated with it in the dietary management of type 1 diabetes mellitus.

Masters Degree. University of KwaZulu-Natal, Pietermaritzburg.Introduction: Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide with an estimated 451 million people currently living with diabetes between the ages of 18-99 years. Approximately 87-91% of people with diabetes in high-income countries have type 2 diabetes mellitus (T2DM), while 7-12% have type 1 diabetes mellitus (T1DM). In South Africa, there are an estimated 2.3 million people living with diabetes and of those people, 5-15% have T1DM. The diabetic should receive individualised nutrition therapy, which includes promoting and supporting healthy eating by achieving and maintaining body weight and individual glycaemic goals. Carbohydrate counting is a meal planning method that alongside the adjustment of insulin assists in managing and maintaining blood glucose levels and is commonly used in the management of T1DM. With carbohydrate counting, the individual is taught to identify carbohydrates in foods (carbohydrate awareness) and determine the amount of carbohydrates that are consumed at one time. They are then taught to give the correct amount of insulin depending on the portion of carbohydrate eaten to prevent hyperglycaemia and hypoglycaemia, and maintain normal blood glucose levels. Carbohydrate counting has been shown to improve glycaemic control as well as quality of life, however, it must be taught by someone who has clinical expertise in the field, such as an experienced registered dietitian. Although international guidelines recommend that carbohydrate counting be offered to all newly diagnosed patients with T1DM, there are currently no recommendations specific to the South African population and little or no information regarding practices and perceptions of dietitians regarding carbohydrate counting. Aim: This study aimed to determine the practices and perceptions of registered dietitians regarding the use of carbohydrate counting and the barriers associated with it in the dietary management of T1DM. It also aimed to determine if there is a need for further training on carbohydrate counting amongst dietitians in KZN. Objectives: i) To determine which dietary management approach is most commonly used by dietitians in KZN when educating patients with T1DM. ii) To determine if dietitians in KZN use carbohydrate counting in the dietary management of patients with T1DM. iii) To determine the perceptions of dietitians in KZN towards the use of carbohydrate counting in the dietary management of T1DM. iv) To determine the barriers which prevent dietitians in KZN from using carbohydrate counting in the dietary management of T1DM. v) To determine if dietitians in KZN see a need for further education/training in the area of carbohydrate counting. Method: A cross-sectional descriptive study was conducted via a link to a questionnaire on SurveyMonkey that was attached to an email. The link was distributed to the dietitians who were members of the Association of Dietetics in South Africa (ADSA) in KZN. The KZN Department of Health (DOH) uploaded the survey on their intranet website under the surveys section, where the DOH dietitians could access the survey. Data was analysed using the IBM Statistical Package for Social Sciences (SPSS) version 26.0. Results: Sixty-nine dietitians participated in the survey, 78% (n=54) of which qualified at the University of KwaZulu-Natal (UKZN). Although the majority (76.8%; n=53) of the dietitians indicated that they gave dietary management advice to patients with T1DM, a significant 85.5% (n=59) indicated that most of their patients presented with T2DM (p<0.05). The glycaemic index, portion control using the healthy eating plate, carbohydrate counting using nutritional labels, carbohydrate counting using household measures and carbohydrate awareness i.e. making patients aware of which foods contain carbohydrate, were all significant dietary management approaches used by dietitians (p<0.05). The majority of the dietitians (60.9%; n=42) indicated that they had not received additional training on diabetes management. Dietitians agreed that they required further training or education on the use of carbohydrate counting as a dietary management approach to manage patients with T1DM (p<0.05). Dietitians agreed that there were numerous barriers to their use of carbohydrate counting in the management of diabetes. These barriers included a lack of training, confidence and experience, patient illiteracy, lack of financial resources, time, blood glucose records and poor patient motivation. Dietitians agreed that carbohydrate counting was useful as a dietary management approach (p<0.05) and that it was an essential part of the dietary management of T1DM (p<0.05). Conclusion: Although dietitians in KZN stated that they used carbohydrate counting as a dietary management method, their practices varied. There was a willingness amongst dietitians working in both the private and public sectors to receive more training on carbohydrate counting and to apply it to patient care. Although dietitians agreed that carbohydrate counting was a useful and essential method in the dietary management of T1DM, a number of barriers prevented the use of this method. A lack of training, confidence and experience influenced whether or not dietitians taught their patients to carbohydrate count. There is a potential for carbohydrate counting to be used by the dietitians in KZN who participated in the study. However, further training and resources are required. This study has highlighted a need for South African guidelines on the dietary management of T1DM, as there is currently none in place

Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells

The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6) and the neurotrophin (NT) Nerve Growth Factor (NGF) for neuronal differentiation

Hypomania-Checklist-33: risk stratification and factor structure in a mixed psychiatric adolescent sample

Background: The 33-item Hypomania Checklist (HCL-33) has been shown to distinguish between adolescent bipolar disorder (BD) and unipolar depression. To investigate the utility of the HCL-33 as a screening tool in routine diagnostics, the frequency and psychopathological characteristics of detected individuals in a mixed psychiatric sample necessitate more examination. Methods: The HCL-33, Children's Depression Inventory, Beck's Anxiety Inventory, and Strengths and Difficulties Questionnaire were completed by 285 children and adolescents (12-18 years) in a mixed psychiatric sample. Applying the proposed HCL-33 cut-off score of ≥ 18, individuals with depressive symptoms were divided into at-risk or not at-risk for BD groups. The factorial structure, sum and factor score correlations with psychopathology, and impact on daily functioning were assessed. Results: 20.6% of the sample met at-risk criteria for BD. These individuals (n = 55) were older, more anxious, and showed more conduct problems vs the not at-risk group (n = 107). A two- and a three-factor model were pursued with the same Factor 1 ("active-elated"). Factor 2 ("risk-taking/irritable") was separated into 2a ("irritable-erratic") and 2b ("outgoing-disinhibited") in the three-factor model. Whereas higher Factor 2 and 2a scores correlated with a broad range of more severe symptomatology (i.e., depression, anxiety, hyperactivity), higher Factor 1 and 2b scores correlated with more emotional and conduct problems, respectively. 51.7% of the sample reported a negative impact from hypomanic symptoms on daily functioning. Limitations: Cross-sectional design and data collection in a single mental health service. Conclusions: The HCL-33 may be a useful tool to improve diagnostics, especially in adolescents with depressive symptoms additionally presenting with anxious symptoms and conduct problems

TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition

The transition between epithelial and mesenchymal phenotypes (EMT) occurs in a variety of contexts. It is critical for mammalian development and it is also involved in tumor initiation and progression. Master transcription factor (TF) regulators of this process are conserved between mouse and human.; From a computational analysis of a variety of high-throughput sequencing data sets we initially inferred that TFAP2A is connected to the core EMT network in both species. We then analysed publicly available human breast cancer data for TFAP2A expression and also studied the expression (by mRNA sequencing), activity (by monitoring the expression of its predicted targets), and binding (by electrophoretic mobility shift assay and chromatin immunoprecipitation) of this factor in a mouse mammary gland EMT model system (NMuMG) cell line.; We found that upon induction of EMT, the activity of TFAP2A, reflected in the expression level of its predicted targets, is up-regulated in a variety of systems, both murine and human, while TFAP2A's expression is increased in more "stem-like" cancers. We provide strong evidence for the direct interaction between the TFAP2A TF and the ZEB2 promoter and we demonstrate that this interaction affects ZEB2 expression. Overexpression of TFAP2A from an exogenous construct perturbs EMT, however, in a manner similar to the downregulation of endogenous TFAP2A that takes place during EMT.; Our study reveals that TFAP2A is a conserved component of the core network that regulates EMT, acting as a repressor of many genes, including ZEB2.; This article has been reviewed by Dr. Martijn Huynen and Dr. Nicola Aceto

CFIm-mediated alternative polyadenylation remodels cellular signaling and miRNA biogenesis

The mammalian cleavage factor I (CFIm) has been implicated in alternative polyadenylation (APA) in a broad range of contexts, from cancers to learning deficits and parasite infections. To determine how the CFIm expression levels are translated into these diverse phenotypes, we carried out a multi-omics analysis of cell lines in which the CFIm25 (NUDT21) or CFIm68 (CPSF6) subunits were either repressed by siRNA-mediated knockdown or over-expressed from stably integrated constructs. We established that >800 genes undergo coherent APA in response to changes in CFIm levels, and they cluster in distinct functional classes related to protein metabolism. The activity of the ERK pathway traces the CFIm concentration, and explains some of the fluctuations in cell growth and metabolism that are observed upon CFIm perturbations. Furthermore, multiple transcripts encoding proteins from the miRNA pathway are targets of CFIm-dependent APA. This leads to an increased biogenesis and repressive activity of miRNAs at the same time as some 3' UTRs become shorter and presumably less sensitive to miRNA-mediated repression. Our study provides a first systematic assessment of a core set of APA targets that respond coherently to changes in CFIm protein subunit levels (CFIm25/CFIm68). We describe the elicited signaling pathways downstream of CFIm, which improve our understanding of the key role of CFIm in integrating RNA processing with other cellular activities

Sleep spindles across youth affected by schizophrenia or anti-N-methyl-D-aspartate-receptor encephalitis

BackgroundSleep disturbances are intertwined with the progression and pathophysiology of psychotic symptoms in schizophrenia. Reductions in sleep spindles, a major electrophysiological oscillation during non-rapid eye movement sleep, have been identified in patients with schizophrenia as a potential biomarker representing the impaired integrity of the thalamocortical network. Altered glutamatergic neurotransmission within this network via a hypofunction of the N-methyl-D-aspartate receptor (NMDAR) is one of the hypotheses at the heart of schizophrenia. This pathomechanism and the symptomatology are shared by anti-NMDAR encephalitis (NMDARE), where antibodies specific to the NMDAR induce a reduction of functional NMDAR. However, sleep spindle parameters have yet to be investigated in NMDARE and a comparison of these rare patients with young individuals with schizophrenia and healthy controls (HC) is lacking. This study aims to assess and compare sleep spindles across young patients affected by Childhood-Onset Schizophrenia (COS), Early-Onset Schizophrenia, (EOS), or NMDARE and HC. Further, the potential relationship between sleep spindle parameters in COS and EOS and the duration of the disease is examined.MethodsSleep EEG data of patients with COS (N = 17), EOS (N = 11), NMDARE (N = 8) aged 7–21 years old, and age- and sex-matched HC (N = 36) were assessed in 17 (COS, EOS) or 5 (NMDARE) electrodes. Sleep spindle parameters (sleep spindle density, maximum amplitude, and sigma power) were analyzed.ResultsCentral sleep spindle density, maximum amplitude, and sigma power were reduced when comparing all patients with psychosis to all HC. Between patient group comparisons showed no differences in central spindle density but lower central maximum amplitude and sigma power in patients with COS compared to patients with EOS or NMDARE. Assessing the topography of spindle density, it was significantly reduced over 15/17 electrodes in COS, 3/17 in EOS, and 0/5 in NMDARE compared to HC. In the pooled sample of COS and EOS, a longer duration of illness was associated with lower central sigma power.ConclusionsPatients with COS demonstrated more pronounced impairments of sleep spindles compared to patients with EOS and NMDARE. In this sample, there is no strong evidence that changes in NMDAR activity are related to spindle deficits

Inflammatory pseudotumor of the liver: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Inflammatory pseudotumor of the liver represents a fairly uncommon pathology. Although it is a benign tumor, the correct diagnosis can be missed.</p> <p>Case presentation</p> <p>We report the case of a 55-year-old Caucasian man, who presented with a one-month history of abdominal pain and weight loss. He was diagnosed with a primary liver tumor by computed tomography and magnetic resonance imaging. Alpha-fetoprotein levels ranged within normal limits. A right posterior sectorectomy was performed. Histopathology revealed an inflammatory pseudotumor of the liver. Our patient remains in good condition one year later.</p> <p>Conclusion</p> <p>Although inflammatory pseudotumor of the liver is usually a benign process, controversy regarding its management still exists. With this case report we review the existing literature and consider hepatectomy as a safe treatment approach.</p

Influence of customer focused mission statement on customer satisfaction

The purpose of this study is to examine the influence of customer-focused mission statements on customer satisfaction in selected cell phone manufacturing companies in the United States. The study employed content analysis for the mission statement and data from America customer satisfaction index (ACSI). In analysing our data, Pearson correlation, and multiple regression techniques were used. The result showed that product and service, technology, philosophy, self-concept, and public image mission statement components are strongly positively correlated with customer satisfaction. Customer, survival, growth and profitability and market mission statement components are insignificantly negatively correlated with customer satisfaction. The study, therefore, recommends that companies that want to remain competitive by enhancing customer satisfaction should formulate mission statements from a customer perspective so that they include product and service, technology, philosophy, self-concept, and public image components. The main limitation of the study represents the sample size and structure. This study empirically investigated the correlation and association of nine mission statement components with customer satisfaction.O