A longitudinal analysis of gross motor coordination in overweight and obese children versus normal-weight peers.

BACKGROUND: The relationship of childhood overweight (OW) and obesity (OB) with motor skill and coordination is gaining due attention; however, longitudinal evidence is currently lacking. OBJECTIVE: The dual purpose of this study was (1) to investigate the short-term evolution in the level of gross motor coordination according to children's weight status, and (2) to identify those factors predicting their gross motor coordination performance over a 2-year interval. SUBJECTS: Participants were 50 children with OW, including 8 with OB (aged 6-10 years at baseline, with 52% boys), and 50 with normal-weight (NW) matched for gender and age. MEASUREMENTS: Anthropometrics (body height, body weight, body mass index (BMI), %body fat) and level of gross motor coordination (Körperkoordinationstest für Kinder, KTK) were assessed in 2007 (baseline) and 2 years later in 2009 (follow-up). At baseline, participants completed a survey based on the Flemish Physical Activity Questionnaire (FPAQ) to obtain socio-demographic information and to determine physical activity levels in diverse domains. RESULTS: The evolution in the level of gross motor coordination over time was strongly related to children's weight status. Participants in the NW group showed more progress than their OW/OB peers, who demonstrated significantly poorer performances. Accordingly, between-group differences in KTK outcomes (that is, raw item scores and total motor quotient) became more evident over time. Multiple linear regression analysis further indicated that, in addition to BMI per se (negative predictor), participation in organized sports within a sports club (positive predictor) determines gross motor coordination performance(s) 2 years later. CONCLUSION: Our results provide conclusive evidence for an increasingly widening gap of OW/OB children's gross motor coordination relative to NW peers across developmental time in the absence of targeted initiatives. Special attention is thus needed for OW/OB children, especially for those not practicing sports in a club environment, in terms of motor skill improvement to promote regular participation in physical activity.

Granulomatous peritoneal disease associated with oxaliplatin-based chemotherapy for ampullary adenocarcinoma: a case report.

Adenocarcinomas of the ampulla of Vater represent only 0.2% of all gastrointestinal cancers. Due to the low incidence no large clinical trials evaluating efficacy of treatments are available. Adjuvant therapy is often administered in patients with stage IB or higher. Oxaliplatin is considered as an effective and well tolerated therapeutic option. Adverse events associated with this therapy include cardio-, neuro-, nephrotoxicity and myelosuppression. Previously granulomatous pulmonary and liver manifestations have been described in oxaliplatin-based chemotherapy. In this report peritoneal manifestation of granulomatous disease associated with oxaliplatin is described for the first time. Sarcoidlike reactions may be misinterpreted as tumour progression or metastatic disease, and may consequently result in over-treatment.

The EPICAL trial, a phase Ib study combining first line afatinib with anti-EGF vaccination in EGFR-mutant metastatic NSCLC.

INTRODUCTION: Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed. PATIENTS AND METHODS: The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis. RESULTS: The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient's sera inhibited the EGFR pathway in tumor cells growing in vitro. CONCLUSIONS: Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.

Cell disruption for microalgae biorefineries.

Microalgae are a potential source for various valuable chemicals for commercial applications ranging from nutraceuticals to fuels. Objective in a biorefinery is to utilize biomass ingredients efficiently similarly to petroleum refineries in which oil is fractionated in fuels and a variety of products with higher value. Downstream processes in microalgae biorefineries consist of different steps whereof cell disruption is the most crucial part. To maintain the functionality of algae biochemicals during cell disruption while obtaining high disruption yields is an important challenge. Despite this need, studies on mild disruption of microalgae cells are limited. This review article focuses on the evaluation of conventional and emerging cell disruption technologies, and a comparison thereof with respect to their potential for the future microalgae biorefineries. The discussed techniques are bead milling, high pressure homogenization, high speed homogenization, ultrasonication, microwave treatment, pulsed electric field treatment, non-mechanical cell disruption and some emerging technologies.

Noradrenergic system in the chicken brain: immunocytochemical study with antibodies to noradrenaline and dopamine-beta-hydroxylase.

A light microscopic immunocytochemical study, using antisera against noradrenaline (NA) and dopamine-beta-hydroxylase (DBH), revealed the noradrenergic system in the brain of the chicken (Gallus domesticus). NA- and DBH-immunoreactive (ir) elements showed a similar distribution throughout the whole brain. The neurons immunoreactive for the monoamine were confined to the lower brainstem, the pons, and the medulla. In the pons, a rather dense group of cells was found in the dorsal, most posterior part of the locus coeruleus and in the caudal nucleus subcoeruleus ventralis. A few labeled cells appeared in and around the nucleus olivaris superior in the most caudal part of the metencephalic tegmentum. In the medulla oblongata, noradrenergic cells could be visualized at the level of the nucleus of the solitary tract and in a ventrolateral complex. Virtually all regions of the brain contained a rather dense innervation by NA- and DBH-immunopositive varicose fibers. Noradrenergic fibers and terminals were especially abundant in the ventral forebrain and in the periventricular hypothalamic regions. DBH-ir and NA-ir fibers, varicosities, and punctate structures could be observed in close association with immunonegative perikarya in several brain regions, more specifically in the ventral telencephalon, in the mid- and tuberal hypothalamic region, and in the dorsal rostral pons. Some perikarya in these brain areas were completely surrounded by noradrenergic structures that formed pericellular arrangements around the cells. The present study on the distribution of the noradrenergic system in the brain of the chicken combined with the results of a previous report on the distribution of L-Dopa and dopamine in the same species (L. Moons, J. van Gils, E. Ghijsels, and F. Vandesande, 1994, J. Comp. Neurol. 346:97-118) offers the opportunity to differentiate between the various catecholamines in the brain of this vertebrate. The results are discussed in relation to catecholaminergic systems previously reported in avian species and in the mammalian brain.

Cognitive impairment in the Amish: a four county survey.

BACKGROUND: The prevalence of probable dementia was determined in a rural, homogeneous community of Amish individuals in the Midwestern USA. The Amish are a genetically isolated group with a low level of formal education (< or = 8 years) and few exposures to modern life, who live in intergenerational setting and have strong social support networks. METHODS: Using community directories, trained interviewers administered the Mini Mental State Examination (MMSE) and a medical history survey to all Amish over 64 years old in a four county area. Individuals with scores < 27 (out of a maximum of 30 points) were given additional neuropsychological tests. Results were reviewed by a neuropsychologist and subjects were classified with regard to probable cognitive impairment. RESULTS: The MMSE scores were inversely related with age and directly with education. The Amish have higher MMSE scores than reported for the general US population. The overall prevalence of probable cognitive impairment for those over 64 years was 6.4%. The prevalence increased with age and lower education and was lowest among married individuals. CONCLUSIONS: The MMSE scores among the Amish were higher than the general population despite their low level of formal education. The lower level of cognitive impairment among the Amish could reflect a lack of inherited susceptibility to dementing diseases, or environmental factors characteristic of their traditional lifestyle. Even among this population with < or = 8 years of formal education, education may protect against cognitive impairment.

Validation of a new antiserum directed towards the synthetic c-terminus of the FOS protein in avian species: immunological, physiological and behavioral evidence.

In the past 10 years, the study of the expression of immediate early genes, such as c-fos, in the brain has become a common method for the identification of brain areas involved in the regulation of specific physiological and behavioral functions. The use of this method in avian species has been limited by the paucity of suitable antibodies that cross-react with the FOS protein in birds. We describe in this paper the preparation of an antibody directed against a synthetic fragment of the protein product of the c-fos gene in chickens (Gallus domesticus). We demonstrate that this new antibody can be used in several avian species to study FOS expression induced by a variety of pharmacological, physiological and behavioral stimuli. Western blot studies indicated that this antibody recognizes a protein of the expected size (47 kDa) but also cross reacts to some extent with proteins of lower molecular weight that share sequence homology with FOS (Fos-related antigens). FOS immunocytochemistry was performed with this antibody in four species of birds in three different laboratories utilizing diverse variants of the immunocytochemical procedure. In all cases the antibody provided a reliable identification of the FOS antigen. The new antibody described here appears to be suitable for the study of FOS expression in several different avian species and situations. It is available in substantial amounts and will therefore make it possible to use FOS expression as a tool to map brain activity in birds as has now been done for several years in mammalian species.

Colocalization of arginine-vasotocin and chicken luteinizing hormone-releasing hormone-I (cLHRH-I) in the preoptic-hypothalamic region of the chicken.

To characterize a possible relationship between chicken luteinizing hormone-releasing hormone-I (cLHRH-I) and arginine-vasotocin (AVT) we performed immunocytochemical double-stainings throughout the preoptic-hypothalamic region of the chicken brain. This study clearly reveals a partial colocalization between both neuropeptides. Single-labeled neurons, containing either cLHRH-I or AVT are found intermingled with double stained cells, immunoreactive (ir) for both peptides. A significant number of double-labeled perikarya is found in the preoptic area, more specifically in the ventral and external portion of the supraoptic nucleus (SOv and SOe) and in the medial preoptic nucleus (MPOv). At the level of the anterior hypothalamus, double-labeled cells are predominantly observed near the third ventricle in the nucleus paraventricularis magnocellularis (PVN) and the nucleus periventricularis hypothalami (PHN). Next to this colocalization, a number of cLHRH-I-ir cell bodies are found in close apposition to AVT-ir fiber profiles in the very same areas. Taken together, these data are the first to provide morphological evidence indicating that the AVT system might be involved in the regulation of cLHRH-I release and thus of reproductive functions in birds.

Thyrotropin-releasing hormone concentrations in different regions of the chicken brain and pituitary: an ontogenetic study.

The regional distribution of thyrotropin-releasing hormone (TRH) was studied in the chicken brain. The hypothalamus and the brain stem contained the highest concentration of TRH. Lower amounts were present in the telencephalon, the optic lobes and the cerebellum. Within the hypothalamus, TRH was most abundant in the median eminence. Other important TRH sites were the nucleus paraventricularis magnocellularis, nucleus periventricularis hypothalami, nucleus ventromedialis hypothalami, nucleus dorsomedialis hypothalami and nucleus preopticus periventricularis. On the 14th day of embryonic development (E14), TRH was mostly found in the brain stem. Towards hatching, TRH concentrations increased gradually in both the hypothalamic area and the brain stem. TRH concentrations in the telencephalon, optic lobes and cerebellum remained low. Pituitaries from E14 to E16 chickens were characterized by a high TRH concentration, whereas hypophyseal TRH concentrations dropped towards hatching. Our results support the hypothesis that TRH exerts both endocrine and neurocrine actions in the chicken. On the other hand, high pituitary TRH concentrations were present when hypothalamic concentrations were low and vice versa. Therefore, the chicken pituitary may function as an important source of TRH during early in ovo development at least until the moment hypothalamic control develops.

Parotid sparing study in head and neck cancer patients receiving bilateral radiation therapy: one-year results.

Many patients with head and neck cancers receive radiation therapy as part of their treatment which frequently causes considerable morbidity, including various degrees of permanent salivary gland dysfunction. Three-dimensional treatment planning [3-DTP] and conformational dose delivery constitute a new therapeutic modality that conforms the high-dose radiation volume to the shape of the tumor volume while minimizing the dose to tissue that is not at risk of containing cancer. The treatment volumes for head and neck tumors as well as parotid glands can be well-defined on cross-sectional CT imaging techniques. The purpose of this investigation is to determine if 3-DTP and conformational dose-delivery could minimize radiation dose and salivary gland dysfunction to contralateral parotid glands in patients with head and neck cancers. Eleven patients with head and neck cancers who required bilateral radiation therapy were treated with 3-DTP. Unstimulated and stimulated bilateral parotid saliva was collected prior to radiotherapy, weekly during treatment, and 1, 3, 6, and 12 months after the completion of radiotherapy. Treated parotid glands received an average dose of 5745 cGy, while spared glands received only 1986 cGy (p < 0.0001). Unstimulated and stimulated parotid flow rates decreased dramatically in treated glands after the initiation of radiotherapy, remained at extremely low rates without any improvements, and were significantly lower at 1 year after radiotherapy compared with baseline. Conversely, parotid flow rates in spared glands underwent mild changes during radiotherapy and were approximately 50% of baseline values. The results of this study suggest that with the use of 3-DTP, contralateral parotid gland function can be partially preserved for at least 1 year in patients with head and neck cancers requiring bilateral radiation.

Fos induction in the Japanese quail brain after expression of appetitive and consummatory aspects of male sexual behavior.

We investigated the expression of Fos, the protein product of the immediate early gene c-fos in the brain of male Japanese quail after they engaged in either appetitive or consummatory sexual behavior (i. e., copulation). For 1 h, castrated males treated with testosterone were either allowed to copulate with a female or to exhibit a learned social proximity response indicative of appetitive sexual behavior. Control birds were either left in their home cage or placed in the experimental chamber but did not exhibit the appetitive sexual behavior because they had never learned it. Fos expression was studied with an immunocytochemical procedure in two sets of adjacent sections through the entire forebrain. These sections were immunolabelled with 2 different antibodies raised against a synthetic fragment corresponding to the 21 carboxy-terminal residues of the chicken Fos sequence. Contrary to the results of a previous study in which gonadally intact birds were used, Fos induction was observed neither in the medial preoptic nucleus nor in the nucleus intercollicularis in birds that had interacted for 1 h with a female. This may be related to a lower frequency of copulation in the testosterone-implanted birds than in intact birds, or to differences in the time the brains were collected after the birds engaged in sexual behavior between the two studies (60 min in this study, 120 min in the previous study). The performance of copulation and/or appetitive sexual behavior increased the number of Fos-immunoreactive cells in the ventral hyperstriatum, medial archistriatum, and nucleus striae terminalis. These increases were observed using both antibodies, although each antibody produced minor differences in the number of Fos-immunoreactive cells observed. Using one of the antibodies, but not the other, increases in Fos immunoreactivity were also observed in the nucleus accumbens and hyperstriatum after either copulation or appetitive sexual behavior. These differences illustrate how minor technical variations in the Fos immunocytochemical procedure influence the results obtained. These differences also show that Fos induction in a number of brain regions is observed after performance of consummatory (copulation) as well as appetitive (looking at the female) sexual behavior. This induction is, therefore, not related solely to the control of copulatory acts but, presumably, also to the processing in a variety of telencephalic association areas of stimuli originating from the female. The observation that increased Fos immunoreactivity is present in birds that had learned the response indicative of appetitive sexual behavior, and not in those that had not learned the behavior, further indicates that it is not simply the sight of the female that results in this Fos induction, but the analysis of the relevant stimuli in a sexually explicit context. Conditioned neural activity resulting from a learned association between the stimulus female and the performance of copulatory behavior may also explain some aspects of the brain activation observed in birds viewing, but not allowed to interact with, the female.

Two-year longitudinal study of parotid salivary flow rates in head and neck cancer patients receiving unilateral neck parotid-sparing radiotherapy treatment.

Radiotherapy (RT) is a common treatment for head and neck cancers, and frequently causes permanent salivary dysfunction and xerostomia. This 2-year longitudinal study evaluated unstimulated and stimulated parotid flow rates in 11 patients with head and neck cancers who received unilateral neck parotid-sparing RT. The results demonstrated that treated parotid glands had essentially no output up to 2 years post-RT. Alternatively, spared parotid flow rates were indistinguishable from pre-RT values at 1 and 2 years post-RT, and increased slightly over time. Total unstimulated and stimulated parotid flow rates 2 years after completion of RT were similar to pre-RT values, suggesting that spared parotid function may compensate for lost function from treated parotid glands. These results demonstrate that unilateral neck parotid-sparing techniques are effective in preserving contralateral parotid glands up to 2 years after the completion of RT.

Ileal carcinoid tumors and intestinal ischemia.

Three patients with carcinoid tumors of the ileum are presented; two had severe intestinal ischemia, one with infarction of the small intestine. In all three cases, histopathological examination revealed elastic vascular sclerosis (EVS) in the mesenteric blood vessels. Intestinal ischemia in the presence of a carcinoid tumor is probably due to a combination of tumoral secretion products, vascular changes, mesenterial retraction and nodal involvement. Selective superior mesenteric artery arteriography is diagnostic. All the reported carcinoid tumors with ischemic manifestations are ileal and invaded the mesentery or had positive nodes or metastases; two-thirds had EVS, and one-third mesenterial vascular luminal narrowing. Intestinal ischemia may be the underlying cause of vague symptoms in patients with a carcinoid tumor. This tumor may be small and must be looked for during laparotomy, mild intestinal ischemia or mesenterial thickening are important signs. Early resection can prevent intestinal complications. An aggressive attitude, including debulking of metastases, is justifiable.

Ipsilateral parotid sparing study in head and neck cancer patients who receive radiation therapy: results after 1 year.

OBJECTIVE: To determine if three-dimensional treatment planning and conformational dose delivery could minimize radiation dose and salivary gland dysfunction to contralateral parotid glands in patients with unilateral head and neck cancers. STUDY DESIGN: Fifteen patients with unilateral head and neck cancers were treated with three-dimensional treatment planning. Unstimulated and stimulated bilateral parotid saliva was collected before radiotherapy, weekly during treatment, and 1, 3, 6, and 12 months after the completion of radiotherapy. RESULTS: Treated parotid glands received an average dose of 4949 cGy, whereas spared glands received only 355 cGy. Unstimulated and stimulated parotid flow rates decreased dramatically in treated glands after the initiation of radiotherapy and were significantly lower at 1 year after radiotherapy compared with baseline. Conversely, parotid flow rates in spared glands underwent mild changes during radiotherapy and were similar at 1 year after radiotherapy compared with baseline. CONCLUSION: Parotid gland function can be preserved for at least 1 year in patients with unilateral head and neck cancers with three-dimensional treatment planning.

Effects of timing and duration of feed restriction during rearing on reproductive characteristics in broiler breeder females.

The objective of this study was to determine whether there exists a critical period during rearing when restricted feeding of broiler breeder hens can be most beneficial on subsequent egg production. Broiler breeder pullets were subjected to combinations of either ad libitum or restricted feeding during three periods before sexual maturity. Body weight gain, feed intake, and egg production were recorded. Ovary and oviduct weights were noted at age of first oviposition. At 15 and 18 wk of age and at age of first oviposition, chicken luteinizing hormone releasing hormone-I (cLHRH-I) in the median eminence and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the pituitary and plasma were determined. The results demonstrated that alternation between ad libitum and restricted feeding during rearing changed the growth curves of the birds. Feed restriction from 7 to 15 wk followed by either ad libitum or restricted feeding led to improved reproductive performance, suggesting that long-term feed restriction may not be necessary to attain good reproductive performance. The birds restricted from 7 to 15 wk of age had higher proportional weights of ovary (> or = 1.7%) and oviduct (> or = 1.58%) at age of sexual maturity. The cLHRH-I levels in the median eminence and gonadotrophin contents in the pituitary followed that of growth in response to feeding levels and timing of feeding and could be related to the timing of the onset of lay. At age of first egg, all groups had similar levels of cLHRH-I, LH, and FSH. However, no clear effect of level of feed intake or time period of restriction could be observed for plasma LH or FSH concentrations.

The influence of pre-radiation salivary flow rates and radiation dose on parotid salivary gland dysfunction in patients receiving radiotherapy for head and neck cancers.

Radiotherapy (RT) used for head and neck cancers causes permanent salivary gland dysfunction (SGD). Previous short-term studies have demonstrated that pre-RT salivary flow rates and the amount of radiation exposure to parotid glands influence the amount of RT-induced SGD. The purpose of this study was to determine which variables are related to the development of long-term post-RT SGD. Parotid flow rates (PFR) were assessed prior to and 1 year after completion of RT in spared parotid glands from 34 patients from 2 parotid-sparing protocols. The results reveal that spared PFR were not significantly higher 1 year post-RT in patients who had high pre-RT PFR, when compared with patients with low pre-RT PFR. However, patients who received higher doses of RT to spared parotid glands had lower PFR 1 year post-RT, compared with patients who had received lower doses of RT. These one-year findings suggest that high pre-RT PFR do not provide protection against RT-induced SGD. Conversely, reduced RT dosages to contralateral parotid glands are protective of PFR after completion of RT.

Possible approaches to develop vaccines against hepatitis A.

More than a decade ago, successful replication of hepatitis A virus (HAV) in cell culture opened the way to the development of live attenuated and inactivated vaccine candidates. Serial passages of HAV in cell culture led to attenuation as demonstrated by experiments in non-human primates. Several live vaccine candidates obtained through serial passages have been evaluated in volunteers. Significant improvements in the yield of viral antigen from infected cell cultures stimulated the development of killed vaccine candidates. These formalin-inactivated vaccines contain the viral capsid antigens assembled into viral particles. The immunogenic potential of the vaccine candidates depends strongly on the preservation of the configuration of the capsid proteins. Synthetic peptides covering immunogenic sequences of VP1 as well as soluble capsid proteins expressed as fusion proteins in Escherichia coli were therefore only weakly immunogenic when injected at high concentrations in rabbits. On the other hand, tamarin monkeys immunized with a live recombinant vaccinia expressing P1 were protected against virulent challenge. There are, however, considerable drawbacks related to the use of live vaccinia as a carrier virus. Chimeric polio-HAV VP1 viruses have been constructed. These hybrid viruses were not able to induce an immune response, probably because of configurational constraints of poliovirus on the inserted HAV epitopes. More recently, encouraging data on empty virus particles expressed in baculovirus and vaccinia virus systems have been reported.