Hippocampal sclerosis dementia: a reappraisal

Hippocampal sclerosis (HpScl) is characterized by neuronal loss and gliosis in CA1 and subiculum of the hippocampus, and may be one contributing factor to dementia in old age. The term hippocampal sclerosis dementia (HpSclD) designates the presence of both hippocampal sclerotic lesions and a dementia syndrome. In the present review, we outline the pathological heterogeneity underlying HpSclD and discuss related disorders due to tau protein pathology and frontotemporal dementia with ubiquitin positive inclusions (FTLD-U). We also provide a detailed morphological description of ten of our own autopsied HpSclD cases, and compare these pathological findings with those reported in the literature. The lateralization of HpScl and the atrophy of the mammillary bodies were striking features in most of our cases. The main pathology consisted of tau positive lesions with a predominance of neuronal and glial pretangles in Ammon's horn and the dentate gyrus. Neurofibrillary and ghost tangles in CA1 and the subiculum were scarce and thus insufficient to explain the hippocampal pyramidal cell loss. In some cases, tau pathology in the hippocampal formation coexisted with glial tau pathology in the frontal cortex. The most striking finding besides the tau pathology was the presence of concomitant neuronal cytoplasmic inclusions and neurites immunoreactive for the transactive response DNA-binding protein-43 (TDP-43) in the dentate gyrus and temporal neocortex, similar to those found in FTLD-U. Taken together, the pathology of HpSclD is indicative of a degenerative rather than a hypoxic/ischemic etiology of HpSclD. Presently, HpSclD may best be deemed a disorder with various neurodegenerative etiologies, most notably tauopathy and TDP-43 proteinopathy (i.e. FTLD-U). Each of these disease processes could either independently or concertedly account for the dementia syndrome in HpScl

A modular LHC built on the DNA three-way junction

A light-harvesting complex composed of a p-stacked multichromophoric array in a DNA three-way junction is described. The modular design allows for a ready exchange of non-covalently attached energy acceptor

Prevention of infectious complications after laparoscopic appendectomy for complicated acute appendicitis—the role of routine abdominal drainage

Purpose: Complicated acute appendicitis is still associated with an increased morbidity. If laparoscopy has been accepted as a valid approach, some questions remain concerning intra-abdominal abscess formation. Routine prophylactic drainage of the abdomen has been proposed. However, this practice remains a matter of debate, poorly validated in the literature. With the present study, we investigated the impact of drainage in laparoscopic appendectomy for complicated appendicitis. Method: This is a case match study of consecutive patients operated on by laparoscopy in a single institution. One hundred and thirty patients operated for complicated appendicitis (local peritonitis without perforation, with perforation, or with periappendicular abscess) with prophylactic intraperitoneal drainage were matched one by one to 130 patients operated without drainage. Uncomplicated appendicitis and generalized peritonitis were excluded. Primary endpoint was surgical complications and secondary endpoints were transit recovery time and length of hospital stay. Results: Patients without drain had significantly less overall complications (7.7% vs. 18.5%, p = 0.01). Moreover, the absence of drainage was of significant benefit for transit recovery time (2.5 vs. 3.5days, p = 0.0068) and length of hospital stay (4.2 vs. 7.3days, p < 0.0001). Conclusion: No benefits were observed for prophylactic drainage of the abdominal cavity during emergency laparoscopic treatment of complicated appendicitis. For this reason, this practice may be abandone

Addition of platinum derivatives to neoadjuvant single-agent fluoropyrimidine chemoradiotherapy in patients with stage II/III rectal cancer: protocol for a systematic review and meta-analysis (PROSPERO CRD42017073064)

Background Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or disease-specific survival. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemoradiotherapy holds the potential of positively affecting survival in this context since it has been proven effective in the palliative and adjuvant setting of colorectal cancer. Thus, the objective of this systematic review is to assess the efficacy, safety, and quality of life resulting from adding a platinum derivative to neoadjuvant single-agent fluoropyrimidine-based chemoradiotherapy in patients with Union for International Cancer Control stage II and III rectal cancer. Methods: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials will be systematically searched to identify all randomized controlled trials comparing single-agent fluoropyrimidine-based chemoradiotherapy to combined neoadjuvant therapy including a platinum derivative. Predefined data on trial design, quality, patient characteristics, and endpoints will be extracted. Quality of included trials will be assessed according to the Cochrane Risk of Bias Tool, and the GRADE recommendations will be applied to judge the quality of the resulting evidence. The main outcome parameter will be survival, but also treatment toxicity, perioperative morbidity, and quality of life will be assessed. Discussion: The findings of this systematic review and meta-analysis will provide novel insights into the efficacy and safety of combined neoadjuvant chemoradiotherapy including a platinum derivative and may form a basis for future clinical decision-making, guideline evaluation, and research prioritization. Systematic review registration PROSPERO CRD4201707306

Argyrophilic grain disease: molecular genetic difference to other four-repeat tauopathies

Argyrophilic grain disease (AgD) is a four-repeat tauopathy that is almost exclusively restricted to allocortical areas. Progressive supranuclear palsy and corticobasal degeneration also show predominant deposition of four-repeat tau filaments, and are associated with the tau H1 haplotype. We investigated a possible association between AgD and the tau H1 haplotype. In AgD, no difference between the prevalence of the tau H1 haplotype or H1/H1 genotype was observed when compared to non-demented control cases. These data suggest that a dysfunction of the tau protein in AgD—in contrast to other four-repeat tauopathies—may arise irrespective of the genetic background regarding the tau H1 or H2 haplotype

Economic- and Non-Economic Goals of Family Firms

Motivated by a lack in the current literature, this thesis reviews academic research on the economic and noneconomic goals of family firms. Heretofore, no detailed overview of different goals embedded in the goal setting-, outcome-, and alignment process has been provided. Using a systematic literature search and review process, I identify 117 relevant studies in the fields of management, economics, and affiliated domains between 1963 and 2018. Beyond a more detailed overview of the current state of research, I outline goal setting, outcomes, alignment, and four different family firm goal classes. Lastly, I show avenues for future research in the family firm–goal field.&nbsp;Motivated by a lack in the current literature, this thesis reviews academic research on the economic and noneconomic goals of family firms. Heretofore, no detailed overview of different goals embedded in the goal setting-, outcome-, and alignment process has been provided. Using a systematic literature search and review process, I identify 117 relevant studies in the fields of management, economics, and affiliated domains between 1963 and 2018. Beyond a more detailed overview of the current state of research, I outline goal setting, outcomes, alignment, and four different family firm goal classes. Lastly, I show avenues for future research in the family firm–goal field.&nbsp; Keywords: Family firms, economic goals, non-economic goals, socioemotional wealth&nbsp

The role of the human acetylation polymorphism in the metabolic activation of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)

The metabolic activation of the heterocyclic food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by two human cytochrome P450 monooxygenases (P4501A1 and P4501A2) and two human N-acetyltransferases (NAT1 and NAT2) was investigated. Various combinations of these enzymes were functionally expressed in COS-1 cells. DNA adducts resulting from the activation of IQ were assayed quantitatively by the 32P-postlabeling procedure. The highest adduct frequency was observed in cells expressing both CYP1A2 and NAT2. CYP1A2 in combination with NAT1 was 3-6 times less active. When expressed alone these enzymes gave rise to low adduct frequencies. Experiments with N-acetyl-IQ as substrate suggest that NAT1 and NAT2 in addition to their known role in N-acetylation display arylhydroxamic acid N,O-acetyttransferase (AHAT) activity. Quantitative differences in adduct formation between IQ and N-acetyl-IQ indicated that metabolic activation of these arylamines preferentially occurs by P4501A2-catalyzed N-hydroxylation followed by O-acetylation mediated through NAT1 and/or NAT2. These data, in combination with the known genetic polymorphism of NAT2, may explain the clinical observation that the acetylation polymorphism constitutes a risk factor in the carcinogenic activation of environmental mutagen

Disease, activity and schoolchildren's health (DASH) in Port Elizabeth, South Africa: a study protocol

BACKGROUND: An in-depth epidemiological investigation on intestinal parasite infections in an impoverished area of Port Elizabeth, South Africa provides a unique opportunity for research on its impact on children's physical fitness, cognitive performance and psychosocial health. Additionally, we will screen risk factors for the development of diabetes and hypertension in adulthood. METHODS/DESIGN: A 2-year longitudinal cohort study will be conducted, consisting of three cross-sectional surveys (baseline and two follow-ups), in eight historically black and coloured (mixed race) primary schools located in different townships in Port Elizabeth, South Africa. Approximately 1000 Grade 4 primary schoolchildren, aged 8 to 12 years, will be enrolled and followed. At each survey, disease status, anthropometry and levels of physical fitness, cognitive performance and psychosocial health will be assessed. After each survey, individuals diagnosed with parasitic worm infections will be treated with anthelminthic drugs, while children with other infections will be referred to local clinics. Based on baseline results, interventions will be tailored to the local settings, embedded within the study and implemented in half of the schools, while the remaining schools will serve as controls. Implementation of the interventions will take place over two 8-week periods. The effect of interventions will be determined with predefined health parameters. DISCUSSION: This study will shed new light on the health burden incurred by children in deprived urban settings of South Africa and provide guidance for specific health interventions. Challenges foreseen in the conduct of this study include: (i) difficulty in obtaining written informed consent from parents/guardians; (ii) administration of questionnaires in schools where three languages are spoken (Afrikaans, Xhosa and English); (iii) challenges in grasping concepts of psychosocial health among schoolchildren using a questionnaire; and (iv) loss to follow-up due to the study setting where illiteracy, mobility and violence are common. Finally, designing the health interventions together with local principals and teachers will allow all concerned with the research to bolster a sense of community ownership and sustained use of the interventions after the study has ceased

Intestinal parasites, growth and physical fitness of schoolchildren in poor neighbourhoods of Port Elizabeth, South Africa: a cross-sectional survey

BACKGROUND: As traditional lifestyle and diets change with social and economic development, disadvantaged communities in low- and middle-income countries increasingly face a double burden of communicable and non-communicable diseases. We studied the relationship between physical fitness and infections with soil-transmitted helminths (STHs), intestinal protozoa and Helicobacter pylori among schoolchildren in Port Elizabeth, South Africa. METHODS: We conducted a cross-sectional survey among 1009 children, aged 9 to 12 years, from eight primary schools in socioeconomically disadvantaged neighbourhoods of Port Elizabeth. Physical fitness was determined using field-deployable tests of the Eurofit fitness test battery. Stool samples were analysed with the Kato-Katz thick smear technique to diagnose STHs and with rapid diagnostic tests (RDTs) to detect intestinal protozoa and H. pylori infections. Haemoglobin (Hb) levels were assessed and anthropometric indicators determined. RESULTS: Complete data were available for 934 children (92 %). In two schools, high STH prevalences were found (Ascaris lumbricoides 60 and 72 %; Trichuris trichiura 65 % each). For boys and girls co-infected with A. lumbricoides and T. trichiura (n = 155) the maximal oxygen uptake (VO2 max) was estimated to be 50.1 and 47.2 ml kg(-1) min(-1), compared to 51.5 and 47.4 ml kg(-1) min(-1) for their non-infected peers (n = 278), respectively. On average, children without helminth infections had greater body mass (P = 0.011), height (P = 0.009) and a higher body mass index (P = 0.024) and were less often stunted (P = 0.006), but not significantly less wasted compared to their peers with a single or dual species infection. Among 9-year-old boys, a negative correlation between helminth infections and VO2 max, grip strength and standing broad jump distance was observed (P = 0.038). The overall mean Hb level was 122.2 g l(-1). In the two schools with the highest prevalence of STHs the Hb means were 119.7 and 120.5 g l(-1), respectively. CONCLUSIONS: Intestinal parasite infections appear to have a small but significant negative effect on the physical fitness of infected children, as expressed by their maximal oxygen uptake. We observed a clear impact on anthropometric indicators