Publishing Nutrition Research: A Review of Epidemiologic Methods

The use of epidemiologic research designs and analytical methods is common in dietetics research. Food and nutrition professionals who seek to perform evidence-based practice or participate in research design, analysis, and communication need skills in the essentials of epidemiology. This is one of a series of monographs on research methodology that addresses these needs and supports the goals of the Board of Editors of the Journal of the American Dietetic Association to further enhance competency and skills. This monograph focuses on statistical approaches for univariate analyses used with the primary observational study designs associated with epidemiology. Tables illustrating the presentation and interpretation of these results are included.     

Neuro-endocrine carcinoma of the nose and paranasal sinuses

The literature on Neuroendocrine carcinoma of the nasal cavity and paranasal sinuses contains a plethora of contradictions concerning their nomenclature, classification, pathogenesis, diagnosis, therapy and prognosis. The term neuroendocrine carcinoma is used for malignant epithelial tumours showing a characteristic microscopic pattern and cytologic features. The idea of presenting this case of neuroendocrine malignancy, which itself is a very rare entity is to emphasise the role of electron microscopy in arriving at a diagnosis and the necessity of adequate surgical excision followed by radiotherapy for a longer tumour free survival.     

Role of Periductal and Ductular Epithelial Cells of the Adult Rat Pancreas in Pancreatic Hepatocyte Lineage: A Change in the Differentiation Commitment

Development of pancreatic hepatocytes in adult rats maintained on copper deficient diet containing 0.6% trien (CuDT) has been reported recently. To elucidate the histogenesis of hepatocytes a sequential study was undertaken using morphologic, histochemical, immunochemical, in situ hybridization, and Northern blot analysis. Male F-344 rats weighing 80 to 90 g were fed CuDT for 8 weeks and returned to normal rat chow. Beginning from 4 weeks of copper depletion, there was a progressive loss of acinar cells and by 8 weeks more than 90% of the acinar tissue was lost. During this period, there was an increase in the number of adipocytes in the interstitium, and in the number of interstitial and ductular cells. Morphologic observations were confirmed by immunoblot and Northern blot analysis, in which the amount of pancreatic proteins and their mRNAs decreased between 5 and 8 weeks. During this period, a progressive increase in the level of albumin mRNA was observed. In situ hybridization, performed at 7 weeks of copper deficiency, showed localization of albumin mRNA over interstitial and ductular cells. Pancreatic hepatocytes were identified immediately after the rats were returned to a normal diet and gradually increased in number. The hepatocytes occupied almost 60% of the pancreatic volume by 8 weeks. During the early recovery phase, hepatocytes were identified in ductules as well as in the interstitium. Based on these studies, it is concluded that both the ductular cells and interstitial cells, which resemble oval cells of liver, are capable of transforming into pancreatic hepatocytes and these cells may be considered stem-cell equivalent.     

Selection for high and low mating propensity inDrosophila ananassae

InDrosophila ananassae, artificial selection was carried out for high and low mating propensity for 15 generations. Response to selection was from about F₅, with rapid divergence in mating frequencies in replicates of both fast and slow lines. To assess the effect of selection on the two sexes, females and males of the selected lines were tested against their respective counterparts of the control line after 15 generations. Significant differences in mating propensity were observed when selected males were tested against the control females, which suggests that males were much more affected by selection than females. After 15 generations the fast and slow lines (both replicates) were crossedinter se and mating frequencies of F₁ hybrids were studied in the same way as during the selection experiment. F₁ flies had a higher mating activity compared to their parental lines when males were derived from fast lines to produce hybrids. On the other hand, F₁ hybrids produced by crossing slow-line males with fast-line females showed mating frequencies similar to those of the slow parental lines. These findings suggest that mating propensity inD. ananassae is under the control of polygenes. Furthermore, the significant differences in mating propensity of hybrids produced by the fast and slow males indicate the possibility of a Y-linked influence on mating propensity inD. ananassae.The present investigation was carried out during the tenure of a senior research fellowship of the CSIR, New delhi, to S.C.     

Effect of gossypol in association with chromium protoporphyrin on heme metabolic enzymes

Gossypol prevents the liberation of oxygen from oxyhemoglobin and exerts a hemolytic effect on erythrocytes. In excessive dosages of gossypol, an extreme burden is placed upon the respiratory and circulatory organs owing to the reduced oxygen carrying capacity of blood. Chromium protoporphyrin (CrPP) has been shown to either competitively suppress or to significantly ameliorate a variety of naturally occurring or experimentally induced forms of jaundice in animals and man. In this communication, a novel tissue dependent response to gossypol (50 micromol/kg bw) and gossypol in association with CrPP (50 micromol/kg bw) is described. Our results revealed that gossypol stimulated the hepatic, splenic, and renal delta-aminolevulinic acid synthase (ALA-S) activity, the heme biosynthetic enzyme, and simultaneous administration of CrPP and gossypol synergized the gossypol-mediated increase of ALA-S activity. Gossypol was found to be a potent stimulator of heme oxygenase (HMOX) activity in rat liver and kidney to varying degrees. This tissue response contrasted with that of the spleen, where gossypol decreased the activity of the enzyme. In consonance with the increased hepatic and renal HMOX activity, a marked increase was observed in total serum bilirubin concentration in gossypol treated rats. When rats were given CrPP simultaneously with gossypol, the gossypol mediated increase in hepatic and renal HMOX activity was effectively blocked. Furthermore, the increase in enzymatic activity was accomplished by a decline in the total microsomal protein content on gossypol administration. These findings emphasize the toxic effect of gossypol in eliciting increased heme degradation by stimulating HMOX activity in the liver and the kidney and the potential usefulness of CrPP in experimental and perhaps clinical conditions in which hyperbilirubinemia occurs.     

Constitutive activation of the PI3K‐AKT pathway and cardiovascular abnormalities in an individual with Kosaki overgrowth syndrome

Kosaki overgrowth syndrome is a recently described syndrome characterized by distinctive facial features, brain white matter lesions, and developmental delay. Germline activating heterozygous PDGFRB mutations have been reported in this condition. Systemic connective tissue‐type findings have been described in some individuals. We describe a 19‐year‐old Caucasian female with a history of hydrocephalus, Dandy–Walker malformation, cervical spine arachnoid cyst, progressive scoliosis, and overgrowth. Her physical exam included distinctive craniofacial dysmorphism, as well as soft and hyperextensible skin. Cardiovascular imaging during adolescence revealed saccular aneurysms in both coronary artery systems and subtle tortuosity of the cervical vertebral arteries. Exome sequencing trio analysis identified a de novo previously reported pathogenic variant in PDGFRB, c.1696T>C (p.[Trp566Arg]). Further functional studies included platelet‐derived growth factor cellular metabolic pathway activity that confirmed the variant causes a constitutive activation of the PI3K‐AKT pathway. This is the first report to characterize the activating nature of this PDGFRB variant. We also highlight the connective tissue findings seen in Kosaki overgrowth syndrome and recommend baseline echocardiographic evaluation in all individuals with this condition with particular emphasis on coronary arteries.     

Immunohistochemical and molecular genetic study on epithelioid glioblastoma: Series of seven cases with review of literature

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup.     

“Locking in” a rare pathogen

Since its identification as a unique species in 1982, Escherichia hermannii has only recently been implicated as a pathogenic organism in human diseases. Literature search indicates removal of hemodialysis catheter as being essential to the success of treatment for bacteremia with this organism. However, having no alternative access for hemodialysis led to the attempt to salvage the catheter with the use of Antibiotic lock therapy. This case highlights Antibiotic lock therapy as an indication in Escherichia hermanii Catheter related Bloodstream infection.