Variant human pancreas: aberrant uncinate process or an extended mesenteric process

Variations in the morphology of pancreas are not very common. We observed a rare variant of the uncinate process of the pancreas that extended in the mesentery of the small intestine. After its origin from the lower part of the head of the pancreas, the mesenteric process (MP) passed over the third part of the duodenum to enter the mesentery of the jejunum and ileum and extended up to the level of the pelvic brim. The branches of the superior mesenteric vessels were embedded in the extended MP of the pancreas. This aberrant extension of the pancreas was drained by a narrow duct, which joined the main pancreatic duct inside the head. We did not observe a separate uncinate process arising from the head. On histology normal acini and endocrine cells were observed in the extension. This variant is important as symptoms of pancreatic disease from such extensions may be confused with other commonly encountered acute or chronic abdominal conditions.     

CD40 activation mediates p53-dependent cell cycle regulation in human multiple myeloma cell lines

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30 degrees C) but not at restrictive (37 degrees C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status.     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.

Goldenhar Syndrome with Tessier’s 7 Cleft: Report of a Case

Goldenhar syndrome, a variant of hemifacial microsomia, is a well-known developmental anomaly of maxillofacial skeleton that is apparent at birth. The first and second branchial arch involvement during early embryonic development results in a wide spectrum of anomalies that may include macrostomia and lateral facial clefts. Though clefts of the orofacial region are among the most common congenital facial defects, the occurrence of lateral facial clefts (Tessier 7 cleft) in conditions such as the Goldenhar syndrome, is very rare (<5%). The lateral facial cleft, which results because of improper development of the perioral muscles of the face, gives an appearance of macrostomia giving rise to potential psychological, aesthetic and feeding problems. This clinical report describes the closure of a Tessier 7 cleft and the use of distraction osteogenesis to treat mandibular asymmetry in an 11-year-old female patient with Goldenhar’s syndrome.     

The systems biology of mitochondrial fission and fusion and implications for disease and aging

Mitochondria organize themselves as dynamic populations within a cell, by undergoing continuous cycles of fission and fusion. The spatio-temporal distribution and abundance of mitochondria determines the cell’s energy budget and is thus intimately linked to the cell’s response to environmental stimuli during aging. The dynamic balance of mitochondrial fission and fusion can be studied in terms of antagonistic subpopulations that regulate the mitochondrial responses in space and time. The dynamic nature of these processes motivates mathematical modelling and the simulation of such complex process. In several neurodegenerative and metabolic diseases the dynamic balance of fission and fusion is disturbed. However, how this dynamics plays a role in the progression of diseases is largely unclear. Fission and fusion help mitochondria to regulate cellular energy (ATP) levels, and minimize accumulation of harmful oxidized material called reactive oxygen species which accelerate mutations in mitochondrial DNA (mtDNA) during aging. We discuss how systems biology approaches can be used to investigate the mechanisms controlling the fission–fusion dynamics under two categories: dissecting the design of its molecular regulatory motifs, and understanding complex mitochondrial responses through their population level interactions. This will help us to understand how different regulatory mechanisms regulate the ATP and mutation (mtDNA) landscape of mitochondria to a variety of environmental stimuli in order to maintain their function during aging.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors

The presence of growth-induced solid stresses in tumors has been suspected for some time, but these stresses were largely estimated using mathematical models. Solid stresses can deform the surrounding tissues and compress intratumoral lymphatic and blood vessels. Compression of lymphatic vessels elevates interstitial fluid pressure, whereas compression of blood vessels reduces blood flow. Reduced blood flow, in turn, leads to hypoxia, which promotes tumor progression, immunosuppression, inflammation, invasion, and metastasis and lowers the efficacy of chemo-, radio-, and immunotherapies. Thus, strategies designed to alleviate solid stress have the potential to improve cancer treatment. However, a lack of methods for measuring solid stress has hindered the development of solid stress-alleviating drugs. Here, we present a simple technique to estimate the growth-induced solid stress accumulated within animal and human tumors, and we show that this stress can be reduced by depleting cancer cells, fibroblasts, collagen, and/or hyaluronan, resulting in improved tumor perfusion. Furthermore, we show that therapeutic depletion of carcinoma-associated fibroblasts with an inhibitor of the sonic hedgehog pathway reduces solid stress, decompresses blood and lymphatic vessels, and increases perfusion. In addition to providing insights into the mechanopathology of tumors, our approach can serve as a rapid screen for stress-reducing and perfusion-enhancing drugs.     

Cortical Tibial Bone Graft for Nasal Augmentation

Background

This study sought to determine the efficacy of cortical tibial bone graft for nasal augmentation. Nine cases of augmentation rhinoplasty with cortical tibial bone graft are presented.

Methods

This prospective study evaluated the postoperative results of nine patients who underwent augmentation rhinoplasty using cortical tibial bone graft. There were six males and three females aged between 21 and 36 years (mean age 29). All the nine cases were treated through closed rhinoplasty incisions.

Results

Nine patients were operated on and the average follow up was 18 months. The results were favorable. The aesthetic results were gratifying; with good nasal projection in every case without any significant postoperative effects or complications requiring surgery were noted during the follow up.

Conclusion

The findings of this study support the use of cortical tibial bone graft for nasal augmentation although further studies with more sample size are required.     

Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism

Autism is a neurodevelopmental disorder associated with social deficits and behavioral abnormalities. Recent evidence suggests that mitochondrial dysfunction and oxidative stress may contribute to the etiology of autism. This is the first study to compare the activities of mitochondrial electron transport chain (ETC) complexes (I–V) and pyruvate dehydrogenase (PDH), as well as mitochondrial DNA (mtDNA) copy number in the frontal cortex tissues from autistic and age-matched control subjects. The activities of complexes I, V and PDH were most affected in autism (n=14) being significantly reduced by 31%, 36% and 35%, respectively. When 99% confidence interval (CI) of control group was taken as a reference range, impaired activities of complexes I, III and V were observed in 43%, 29% and 43% of autistic subjects, respectively. Reduced activities of all five ETC complexes were observed in 14% of autistic cases, and the activities of multiple complexes were decreased in 29% of autistic subjects. These results suggest that defects in complexes I and III (sites of mitochondrial free radical generation) and complex V (adenosine triphosphate synthase) are more prevalent in autism. PDH activity was also reduced in 57% of autistic subjects. The ratios of mtDNA of three mitochondrial genes ND1, ND4 and Cyt B (that encode for subunits of complexes I and III) to nuclear DNA were significantly increased in autism, suggesting a higher mtDNA copy number in autism. Compared with the 95% CI of the control group, 44% of autistic children showed higher copy numbers of all three mitochondrial genes examined. Furthermore, ND4 and Cyt B deletions were observed in 44% and 33% of autistic children, respectively. This study indicates that autism is associated with mitochondrial dysfunction in the brain.