Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

Open-field behavior, habituation and passive avoidance learning: Effect of ACTH and hydrocortisone on Normal and adrenalectomized rats

Exploratory behavior (GMA) and habituation rate (IH) were studied in an open-field situation in normal and adrenalectomized rats. Following this procedure the rats were subjected to passive avoidance learning (PA). Wide-spreading individual differences were observed in the exploratory behavior and the tendency of habituation of normal rats. As compared to the normal values, either the adrenalectomy which was performed 24 hr, 7 days and 28 days prior to the experiments or the ACTH and hydrocortisone treatment failed to modify the GMA and the IH significantly. An improvement of PA was found in the normal rats following ACTH and hydrocortisone treatment. In the adrenalectomized animals the hydrocortisone proved to be effective, whereas ACTH did not influence PA. No correlation was found between GMA, IH versus PA values and the influence of ACTH and hydrocortisone administration on these parameters. It is concluded that the direction of PA is unpredictable on the basis of the open-field test performed on R-Amsterdam strain of rats, and the effect of ACTH on passive avoidance learning is mediated through the adrenal glands.     

Stem cell therapy for neurodegenerative diseases: the issue of transdifferentiation

In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation (adult cell acquisition of new unexpected identities) may explain therapeutic success, in addition to replacement of lost cells. This issue needs to be clarified further to maximize the potential for effective therapies. Preliminary stem transplantation trials have already been performed for some neurodegenerative diseases. There is no effective pharmacological treatment for amyotrophic lateral sclerosis, but recent preliminary data both in experimental and clinical settings have targeted it as an ideal candidate disease for the development of stem cell therapy in humans. This review summarizes recent advances gained in stem cell research applied to neurodegenerative diseases with a special emphasis to the criticisms put forward.     

c-kit Expression in small cell carcinoma of the urinary bladder: prognostic and therapeutic implications.

The prognosis for small cell carcinoma of the urinary bladder is poor, and strategies for improved therapy are needed. Targeted therapy against the c-kit proto-oncogene has been successful in the management of gastrointestinal stromal tumor. We investigated the expression of c-kit in 52 cases of small cell carcinoma of the urinary bladder. Specimens with more than 10% of cells demonstrating strong membrane staining were considered to have positive immunostaining for c-kit. c-kit expression was detected in 21 of 52 specimens from these patients. Among the 21 specimens, seven had less than 10% staining, and were considered to be negative. Nine had 11-50% staining, and five had more than 50% staining. Overall, 14 of 52 (27%) small cell carcinomas of the urinary bladder were positive for c-kit expression. During a median follow-up of 11 months, 60% of the patients died of bladder cancer. No association was found between c-kit expression and survival or other clinicopathologic parameters. Five-year cancer-specific survivals for c-kit-positive and c-kit-negative tumors were 9 and 15%, respectively (P=0.36). A significant proportion (27%) of small cell carcinomas of the urinary bladder expressed c-kit, suggesting that it may prove useful as a therapeutic target in small cell carcinoma of the urinary bladder.     

Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families

Chronic distal spinal muscular atrophy (Chronic DSMA, MIM (*)607088) is a rare autosomal recessive disorder characterized by a progressive motor weakness and muscular atrophy, predominating in the distal parts of the limbs. A form of Chronic DSMA gene has been previously mapped to chromosome 11q13 in the 10.3 cM interval defined by loci D11S1889 and D11S1321. By linkage analysis in 12 European Chronic DSMA families, we showed that a disease gene maps to chromosome 11q13.3 (Z(max)=6.66 at theta=0.00 at the DSM4 locus) and suggested that this condition is genetically homogeneous. Recombination events allowed us to reduce the genetic interval to a 2.6 cM region, telomeric to the IGHMBP2 gene, excluding this gene as the disease causing gene in Chronic DSMA. Moreover, partial linkage disequilibrium was found between three rare alleles at loci D11S1369, DSM4 and D11S4184 and the mutant chromosome in European patients. Analysis of the markers at these loci strongly suggests that most Chronic DSMA chromosomes are derived from a single ancestor. Refinement of the Chronic DSMA locus will hopefully allow to test candidate genes and lead to identification of the disease-causing mutations.     

Correlation between the course of the medial plantar artery and the morphology of the abductor hallucis muscle

The abductor hallucis muscle flap is commonly used as a proximally-based flap in the management of ankle, heel, and midfoot lesions, where it is ideally suited for closing defects. This study investigates the anatomical details of this muscle in 13 fresh male cadavers. The medial plantar artery (MPA) was studied by dissection and macroscopic analyses to document the relationship of its superficial and deep branches with respect to the abductor hallucis muscle (AHM). Three main patterns could be described. In Pattern A (54%) the MPA divides into two branches. The deep branch reaches the deep surface of the AHM, supplying its proximal part, and the superficial branch courses between the AHM and the flexor digitorum brevis, to end as the first plantar metatarsal artery. The latter supplies two to three small branches to the distal part of the AHM. The fibers of the AHM end symmetrically on the two sides of the tendon and the muscle presents an arciform shape. The MPA, in Pattern B (38%), lacks a deep branch and continues along the lateral border of the AHM as a superficial branch that supplies proximal and distal collaterals to the muscle. The muscle fibers of the AHM end mainly on the medial side of the tendon. The muscle belly presents an arciform shape and is located on the medial margin of the foot superomedially with respect to Pattern A. In Pattern C (8%) the MPA continues as a large deep branch on the deep surface of the AHM and ends as the medial collateral artery of the big toe. A smaller superficial branch of the MPA provides a few collaterals to the AHM from its proximal part and to the flexor digitorum brevis in its distal part. The AHM fibers end mainly on the lateral side of the tendon and morphologically the muscle presents a straight line on the sole of the foot compared to Pattern A. Although Patterns B and C, from a surgical point of view, necessitate interruption of the main trunk of the MPA, Pattern A may permit the vascularization of the muscles of the medial side of the sole of the foot by the superficial trunk of the MPA. Because preoperative radiological study of the plantar vessels correlate with the morphological characteristics of the AHM observed during surgery, such imaging may be useful in determining the appropriate flap design based on the patient's unique pattern of MPA branching.     

Comparative in vitro study on a ultra-high roughness and dense titanium coating

A new implant surface has been developed with the purpose of avoiding as much stress shielding as possible, and thus prolong the prosthesis lifespan. The aim of this study was to investigate the in vitro effect of this new ultra-high roughness and dense Titanium (Ti) surface (PG60, Ra = 74 microm) in comparison with medium (TI01, Ra = 18 microm) and high (TI60, Ra = 40 microm) roughness and open porous coatings; all the coatings were obtained by vacuum plasma spraying. MG63 osteoblast-like cells were seeded on the tested materials and polystyrene, as control, for 3 and 7 days. Cells proliferated on the material surfaces similarly to the control. Alkaline phosphatase activity had lower values for TI60 than TI01 (p < 0.0005) and PG60 (p < 0.005). Osteocalcin levels measured on TI60 were significantly (p < 0.0005) lower in comparison with TI01 and PG60 at 7 days. Procollagen-I synthesis reduced with increasing roughness and the lowest data was found for PG60. While at 3 days Transforming Growth Factor beta1 levels augmented with increasing roughness, at 7 days TI60, the high roughness surface, was significantly lower than PG60 (p < 0.005) and TI01 (p < 0.001). All tested materials showed significantly higher Interleukin-6 levels than those of polystyrene at both experimental times. Nitric Oxide activity on TI01 was significantly (p < 0.05) higher than on TI60 and polystyrene. In conclusion, the new ultra-high roughness and dense coating PG60 provided a good biological response, even though, at least in vitro, it behaved similarly to the coatings already used in orthopaedics.     

Geodemographic analysis of pediatric firearm injuries in Miami,FL

PurposeFirearm injuries (GSW) are a growing public health concern and leading cause of morbidity and mortality among children, yet predictors of injury remain understudied. This study examines the correlates of pediatric GSW within our county.MethodsWe retrospectively queried an urban Level 1 trauma center registry for pediatric (0–18 years) GSW from September 2013 to January 2019, examining demographic, clinical, and injury information. We used a geographic information system to map GSW rates and perform spatial and spatiotemporal cluster analysis to identify zip code “hot spots.”Results393 cases were identified. The cohort was 877% male, 87% African American, 10% Hispanic, and 22% Caucasian/Other. Injuries were 92% violence-related and 4% accidental, with 63% occurring outside school hours. Mortality was 12%, with 53% of deaths occurring in the resuscitation unit. Zip-level GSW rates ranged from 0 to 9 (per 1000 < 18 years) by incident address and 0–6 by home address. Statistically significant hot spots were in predominantly underserved African American and Hispanic neighborhoods.ConclusionsGeodemographic analysis of pediatric GSW injuries can be utilized to identify at-risk neighborhoods. This methodology is applicable to other metropolitan areas where targeted interventions can reduce the burden of gun violence among children.Type of studyRetrospective study.Level of evidenceLevel III.     

Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.