Changes in body composition and fat distribution in response to weight loss and weight regain

This thesis describes the effects of weight loss and subsequent weight regain on body composition, fat distribution and resting energy expenditure in moderately obese men and moderately obese premenopausal women. Participants were subjected to a controlled 4.2 MJ/day energy deficit diet for 13 weeks, and re-examined more than one year after weight loss intervention. Five techniques to assess the changes in body composition after weight loss (on average 12.2 ± 3.7 kg (mean ± SD)) were compared. The results from densitometry (hydrostatic weighing) and the deuterium oxide dilution technique were similar, whereas, bioelectrical impedance and two anthropometric methods (skinfold thicknesses and body mass index) showed larger reductions in fat-free mass (FFM) than estimated by densitometry and the dilution technique. These findings were similar in both sexes. Magnetic resonance imaging (MRI) was used to assess the reductions after weight loss in the visceral and subcutaneous abdominal fat depots and the subcutaneous fat depot at trochanter level. The proportional reduction of fat was largest in the visceral depot (men 40%, women 33%) and less fat was lost subcutaneously, especially at trochanter level (men 29%, women 26%). The reductions in visceral fat as measured by MRI were compared with changes in anthropometric measurements. The change in waist-to-hip ratio (WHR) was not related to the change in visceral fat, and the change in sagittal-to-transverse abdominal diameter ratio was only moderately associated with visceral fat loss in both sexes. During the follow-up of 67 weeks after weight loss, 80% of the weight lost was regained on average. In men but not in women, the reduction in resting metabolic rate (RMR) after weight loss was larger than expected from the losses of FFM and fat mass. The RMR returned to baseline level in both sexes after weight regain. The reduction in RMR was not related to later weight regain. Percentage body fat and amount of visceral fat also nearly returned to the level similar to that before weight loss.It is concluded that bioelectrical impedance and anthropometric measurements are not as good as densitometry or the deuterium-oxide dilution method for the evaluation of changes in body composition. Only approximate estimates of visceral fat can be achieved by anthropometry. As a consequence, the assessment of changes in visceral fat by anthropometry is limited. Finally, one weight cycle as observed in this study does not lead to a permanently reduced RMR, nor to a greater body fatness nor to an increase in visceral fat compared with initial levels

In vitro antischistosomal activity of Artemisia annua and Artemisia afra extracts

Background Schistosomiasis, a neglected tropical disease, imposes substantial health and economic burdens on impoverished groups living in predominantly rural areas. Praziquantel (PZQ) is the only drug available for treatment, and it is not completely efficacious. Artemisia annua and Artemisia afra infusions were proposed to possess antischistosomal activities in a recently retracted publication of a clinical trial, leading to our investigation in vitro. Objective The objective was to identify the main components of the infusions and evaluate the in vitro antischistosomal activities of traditionally prepared infusions as well as hexane and dichloromethane (DCM) extracts of the infusions of A. afra and A. annua. Methods Infusions of A. afra and A. annua were submitted to liquid-liquid partitioning with n-hexane and DCM to provide samples for in vitro bioassays using newly transformed schistosomulas (NTS) and adult Schistosoma mansoni worms obtained from infected mice. The viability of the NTS and adult S. mansoni was visually scored via microscopic readout. Results Nine phytochemicals comprising coumarins and organic acids were identified. A. afra and A. annua infusions and extracts possess potent in vitro antischistosomal activities against NTS, at 100 μg/ml. However, the A. afra infusions exhibited better activities against NTS than the A. annua infusion. The A. afra hexane- and DCM extracts presented IC50 values that are similar to PZQ (1.5 μg/ml) and approximately five times lower than the comparison drug artesunate (11.6 μg/ml) against NTS. Low IC50 values for both these extracts were also obtained in phenotypic assays with adult S. mansoni. Conclusion A. afra shows greater antischistosomal potential than A. annua. Thus, further studies are necessary to identify the active molecule(s) responsible for the notable antischistosomal activity of A. afra

Breast cancer risk among first-generation migrants in the Netherlands

We investigated breast cancer incidence in migrants in the Netherlands in 1988-1998. The standardised incidence ratio for breast cancer in Northwest-Netherlands was statistically significantly reduced for women born in Surinam (0.56), Turkey (0.29) and Morocco (0.22). The proportion of women with advanced stages (III and IV) did not differ significantly between migrants and women born in the Netherlands

Ionospheric quasi-static electric field anomalies during seismic activity in August–September 1981

The paper proposes new results, analyses and information for the plate tectonic situation in the processing of INTERCOSMOS-BULGARIA-1300 satellite data about anomalies of the quasi-static electric field in the upper ionosphere over activated earthquake source regions at different latitudes. The earthquake catalogue is made on the basis of information from the United State Geological Survey (USGS) website. The disturbances in ionospheric quasi-static electric fields are recorded by IESP-1 instrument aboard the INTERCOSMOS-BULGARIA-1300 satellite and they are compared with significant seismic events from the period 14 August–20 September 1981 in magnetically very quiet, quiet and medium quiet days. The main tectonic characteristics of the seismically activated territories are also taken in account. The main goal of the above research work is to enlarge the research of possible connections between anomalous vertical electric field penetrations into the ionosphere and the earthquake manifestations, also to propose tectonic arguments for the observed phenomena. The studies are represented in four main blocks: (i) previous studies of similar problems, (ii) selection of satellite, seismic and plate tectonic data, (iii) data processing with new specialized software and observations of the quasi-static electric field and (iiii) summary, comparison of new with previous results in our studies and conclusion. We establish the high informativity of the vertical component <i>Ez</i> of the quasi-static electric field in the upper ionosphere according observations by INTERCOSMOS-BULGARIA-1300 that are placed above considerably activated earthquake sources. This component shows an increase of about 2–10 mV/m above sources, situated on mobile structures of the plates. The paper discusses the observed effects. It is represented also a statistical study of ionospheric effects 5–15 days before and 5–15 days after the earthquakes with magnitude M 4.8–7.9

Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1

Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon autosomal-recessive multisystem disease caused by mutations in SMARCAL1 (swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), a gene encoding a putative chromatin remodeling protein. Neurologic manifestations identified to date relate to enhanced atherosclerosis and cerebrovascular disease. Based on a clinical survey, we determined that half of Schimke immuno-osseous dysplasia patients have a small head circumference, and 15% have social, language, motor, or cognitive abnormalities. Postmortem examination of 2 Schimke immuno-osseous dysplasia patients showed low brain weights and subtle brain histologic abnormalities suggestive of perturbed neuron-glial migration such as heterotopia, irregular cortical thickness, incomplete gyral formation, and poor definition of cortical layers. We found that SMARCAL1 is highly expressed in the developing and adult mouse and human brain, including neural precursors and neuronal lineage cells. These observations suggest that SMARCAL1 deficiency may influence brain development and function in addition to its previously recognized effect on cerebral circulation

BDNF signaling in the VTA links the drug-dependent state to drug withdrawal aversions

Drug administration to avoid unpleasant drug withdrawal symptoms has been hypothesized to be a crucial factor that leads to compulsive drug-taking behavior. However, the neural relationship between the aversive motivational state produced by drug withdrawal and the development of the drug-dependent state still remains elusive. It has been observed that chronic exposure to drugs of abuse increases brain-derived neurotrophic factor (BDNF) levels in ventral tegmental area (VTA) neurons. In particular, BDNF expression is dramatically increased during drug withdrawal, which would suggest a direct connection between the aversive state of withdrawal and BDNF-induced neuronal plasticity. Using lentivirus-mediated gene transfer to locally knock down the expression of the BDNF receptor tropomyosin-receptor-kinase type B in rats and mice, we observed that chronic opiate administration activates BDNF-related neuronal plasticity in the VTA that is necessary for both the establishment of an opiate-dependent state and aversive withdrawal motivation. Our findings highlight the importance of a bivalent, plastic mechanism that drives the negative reinforcement underlying addiction

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery &lt; 9 and 17% ADL index &lt; 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age &gt; 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.</p

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery &lt; 9 and 17% ADL index &lt; 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age &gt; 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.</p