Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility.

Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed "ATAC-array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

Cadaveric simulation: a review of reviews.

BACKGROUND: Traditional surgical training, largely based on the Halstedian model "see one, do one, teach one" is not as effective in the era of working time restrictions and elaborate shift-patterns. As a result, contemporary surgeons turned to educational methods outside the operating theatre such as simulation. Cadavers are high fidelity models but their use has ethical and cost implications and their availability may be limited. In this review, we explore the role of cadaveric simulation in modern surgical education. METHODS: All the Evidence-Based Medicine databases were searched for relevant reviews. The resulting studies were assessed for inclusion to this review, according to pre-determined criteria. Data extraction was performed using a custom-made spreadsheet, and the quality of included reviews was assessed using a validated scoring system (AMSTAR). RESULTS: The literature review yielded 33 systematic reviews; five of which matched the inclusion criteria and were included in this review of reviews. Cadaveric simulation was found to have good face (subjective assessment of usefulness) and content validity (whether a specific element adds or retracts to the educational value) while trainees improved their surgical skills after practicing on cadavers. However, concerns have been raised about ethical issues, high cost and availability. CONCLUSION: Cadavers are an effective medium for surgical teaching, and it may be appropriate for them to be used whenever surrounding conditions such cost and availability allow. Further research is required to provide evidence on whether there is equivalence between cadavers and other educational media which may not bear the same shortcomings.

Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component.

alpha(1)-Adrenoceptor antagonists, have been documented to induce apoptosis and reduce prostate tumor vascularity in benign and malignant prostate cells. The quinazoline based alpha(1)-antagonists, doxazosin and terazosin but not tamsulosin (a sulphonamide derivative) suppress prostate growth without affecting cell proliferation. These quinazoline-mediated apoptotic effects occur via an alpha(1)-adrenoceptor independent mechanism potentially involving activation of the TGF-beta signal transduction pathway. This review discusses the current knowledge of the action of quinazoline-derived alpha(1)-adrenoceptor antagonists in the benign and malignant prostate and their potential therapeutic use in the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. Finally, a molecular pathway is proposed for their observed apoptotic function against prostate cells. Increased understanding of the action of these established and clinically accepted agents would provide a basis for the design of safe, effective therapeutic regimens in the treatment of prostatic diseases.

Concealed umbilical stoma: long-term evaluation of stomal stenosis.

PURPOSE: The technique of forming a concealed umbilical stoma has been described previously and includes a posterior umbilical flap for improved cosmesis and stenosis prevention. We assessed long-term stomal stenosis. MATERIALS AND METHODS: We reviewed retrospectively the charts of 46 patients (mean age at surgery 14 years) of whom 35 had undergone concealed umbilical stoma creation and 11 the Malone antegrade continence enema procedure for continent urinary diversion. Urinary stomas were created from appendix in 20 cases, ileum in 8, sigmoid colon in 5, bladder in 1 and stomach in 1. Malone antegrade continence enema stomas were constructed from appendix in 10 cases and sigmoid colon in 1. A total of 21 patients underwent urinary diversion and augmentation cystoplasty. RESULTS: At followup of 12 to 84 months (median 3.4 years) 93.5% of patients had an intact stoma with no need for surgical revision. Of the remaining patients 3 (6.5%) required revision of the stoma at skin level for stomal stenosis at 1, 4 and 38 months after initial surgery and 2 had a brief period of indwelling catheterization for correction of stenosis. CONCLUSIONS: The concealed umbilical stoma technique provides an excellent cosmetic result with a low rate of stomal stenosis in patients requiring intermittent bladder or bowel catheterization.

Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia.

BACKGROUND: Medical treatment of benign prostatic hyperplasia (BPH) targets relief of symptoms by causing either relaxation of the prostatic smooth muscle with alpha1 adrenergic blockade, or shrinkage of the gland with 5alpha-reductase inhibitors. We recently demonstrated that alpha1-blockers, such as terazosin, induce apoptosis in prostatic cells. In this study, we examined the combined effect of finasteride and terazosin on the rate of apoptosis and cellular proliferation to investigate their potential synergy at the cellular level. METHODS: Prostate specimens were obtained from men who were treated with either finasteride (n = 24), terazosin (n = 42), or combination therapy (n = 10) for varying time periods (1 week to 36 months) for the relief of the symptoms of BPH. The proliferative and apoptotic indices of both stromal and epithelial prostatic cell populations were determined. Antibodies against TGF-beta1 and TbetaRII were used to examine the immunoreactivity of TGF-beta1 and TbetaRII, respectively, in all prostate tissue sections. RESULTS: The apoptotic index in both prostate cell populations was significantly higher following the combination treatment compared to terazosin or finasteride alone. There were no significant changes in the rate of cellular proliferation with any treatment. Furthermore, there was a significant increase in TGF-beta1 expression in the prostates of patients treated with terazosin or combination therapy, while there was no change in TbetaRII expression. CONCLUSIONS: These results support the concept that induction of prostate apoptosis is a potential molecular mechanism underlying the combination effect of alpha1 blockade with 5alpha-reductase inhibitors in the effective treatment of BPH. The upregulation of TGF-beta1 implies a role for this ligand as an effector of apoptosis induction in response to alpha1-blockade or finasteride therapy of BPH patients.

Bilateral nephrectomy with concomitant renal graft transplantation for autosomal dominant polycystic kidney disease.

PURPOSE: There has been controversy about pre-transplant nephrectomy in patients with autosomal dominant polycystic kidney disease. Kidneys may be removed in these patients when they cause respiratory compromise, early satiety, increased abdominal girth, pain, hematuria or recurrent infection. We determined whether concomitant bilateral nephrectomy at renal transplantation is safe and efficacious. MATERIALS AND METHODS: Between December 1996 and January 1999, 10 patients with autosomal dominant polycystic kidney disease underwent bilateral nephrectomy with concomitant renal grafting (group 1). We compared these patients to 9 with autosomal dominant polycystic kidney disease matched for age and gender who underwent transplantation only (group 2) and 4 with the same condition who underwent bilateral nephrectomy and renal transplantation as staged procedures (group 3). RESULTS: No patients died perioperatively. There was a lower rate of complications in group 1 than in groups 2 or 3. The only significant differences in intraoperative and perioperative parameters were operative time and intraoperative blood loss, which were greater in group 1 than in group 2. We noted no significant differences in groups 1 and 3. Patient satisfaction analyzed by a survey revealed that the 70% of group 1 patients who responded were satisfied with kidney removal and 7 of the 9 in group 2 desired native kidney removal. All group 3 patients already had a functioning renal graft but were satisfied with native kidney removal, although they would rather have undergone bilateral nephrectomy at transplantation. CONCLUSIONS: Our data imply that there is no higher morbidity or mortality when performing concomitant bilateral nephrectomy at renal transplantation in patients with renal failure due to autosomal dominant polycystic kidney disease. There was a higher rate of satisfaction in patients who underwent nephrectomy and transplantation simultaneously, while those who did not undergo concomitant procedures strongly desired to have had that option. Bilateral nephrectomy may alleviate symptoms while providing greater room for renal graft placement. When done without transplantation, bilateral nephrectomy resulted in the highest number of complications. Our data indicate that if bilateral nephrectomy is performed as an adjunct to transplantation, it should be done at renal grafting.

Standardization model for describing the extent of burn injury to human remains.

This paper provides a model for standardizing descriptions of the extent of burn injury to human bodies consumed in fire. Its intent is to simplify and make comparable case reports and legal descriptions by medical examiners, pathologists, crime scene investigators, forensic odontologists, forensic anthropologists, fire fighters, paramedics, and others responsible for recovery, analysis, or identification of burn victims. The Crow-Glassman scale (CGS) is divided into five levels depicting increasing destruction to the body relative to burn injury. Each level relates to a unique set of circumstances that may affect on the recovery procedure, analysis strategy for identification, and choice of personnel most suited for making identifications.

The effects of educational placement and grade level on the self-perceptions of low achievers and students with learning disabilities.

Previous studies have yielded mixed findings as to the effect of learning disabilities (LD) on self-perception. We proposed that perceived competence in children who experience learning difficulties is affected both by age trends in self-appraisal processes and by the degree to which students' salient reference group is composed primarily of similar or more competent others. Measures of perceived competence (Harter, 1982) and perceived achievement were administered to 222 Israeli students (127 boys, 95 girls) in Grades 3, 5, and 7. The sample comprised 68 children with LD attending special schools, 68 children with LD attending special classes in regular schools, and 86 nonidentified low achievers in regular classes. As expected, perceived competence was similar and high in all groups at Grade 3, but was higher among the special school group than among the special class and low achieving groups at Grade 5. The benefits of special schools were less clear at Grade 7. Implications for research methodology and educational practice are discussed.

Handedness and the bilateral asymmetry of the jugular foramen.

This paper examines the proposed association of bilateral asymmetry of the jugular foramen as an indicator of handedness observable from cranial morphology. The jugular foramina of 54 subjects were observed for size asymmetry during routine autopsy procedures. Hand preference data were collected on each subject from family members. Of the 54 subjects, 47 were documented as being right-handed and 7 as being left-handed. These values approximate the average percentage of right-handed versus left-handed individuals from larger populations. Jugular foramen asymmetry was qualitatively identified for 36 subjects (66.7%) and was judged equivocal for the other 18 (33.3%). Of the 36 subjects exhibiting asymmetry, 28 (77.7%) showed positive correlation between the asymmetry direction and handedness. This moderate level of congruence, coupled with the result that 4 of the 7 left-handers exhibited dominant right-side foramina, casts doubt on the reliable use of jugular foramen asymmetry for estimating handedness.

High-energy orbital dislocations: the possibility of traumatic hypertelorbitism.

In a 4-year period from 1983 to 1987, 7160 patients with blunt injuries were admitted to the Maryland Institute of Emergency Medical Services Systems Shock Trauma Center. Facial injuries occurred in 10 percent of this population. High-energy fractures (characterized by computed tomography) were seen in approximately 10 percent of these patients. In this high-energy group, five cases of high-energy orbital dislocations, some representing examples of traumatic hypertelorbitism, were observed. They represent 1.5 percent of the 342 midface fractures observed and 4.8 percent of the naso-orbital ethmoid fractures observed (105 patients). One additional patient is described who was seen at the UCLA Medical Center for late repair of the condition. High-energy impacts of the upper midface created fractures of both orbits, zygomas, and nasoethmoidal regions permitting lateral transposition, enlargement, and divergence of the orbits. Interorbital, intercanthal, and interpupillary distances were increased, criteria that confirm the diagnosis of hypertelorbitism. Fifty percent of the patients were bilaterally blind, and one patient sustained unilateral blindness.

Management of the medial canthal tendon in nasoethmoid orbital fractures: the importance of the central fragment in classification and treatment.

The medial canthal tendon and the fragment of bone on which it inserts ("central" fragment) are the critical factors in the diagnosis and treatment of nasoethmoid orbital fractures. The status of the tendon, the tendon-bearing bone segment, and the fracture pattern define a clinically useful classification system. Three patterns of fracture are appreciated: type I--single-segment central fragment; type II--comminuted central fragment with fractures remaining external to the medial canthal tendon insertion; and type III--comminuted central fragment with fractures extending into bone bearing the canthal insertion. Injuries are further classified as unilateral and bilateral and by their extension into other anatomic areas. The fracture pattern determines exposure and fixation. Inferior approaches alone are advised for unilateral single-segment injuries that are nondisplaced superiorly. Superior and inferior approaches are required for displaced unilateral single-segment injuries, for bilateral single-segment injuries, and for all comminuted fractures. Complete interfragment wiring of all segments is stabilized by junctional rigid fixation. All comminuted fractures require transnasal wiring of the bones of the medial orbital rim (medial canthal tendon-bearing or "central" bone fragment). If the fracture does not extend through the canthal insertion, the canthus should not be detached to accomplish the reduction.

Malignant melanoma.

The incidence of malignant melanoma is increasing faster than that of any other cancer except lung cancer in women. Understanding malignant melanoma and recognizing suspicious lesions is critical in curtailing the spread of this potentially fatal disease.

Rigid stabilization of sagittal fractures of the maxilla and palate.

Rigid stabilization of sagittal fractures of the palate is described that utilizes plate and screw fixation in the palatal vault. Accurate reduction of facial width is obtained, and stability is significantly enhanced. An existing laceration or a longitudinal incision in the palatal mucoperiosteum provides exposure for maxillary adaption plate application. The transpalatal reduction should be supplemented by fixation at the piriform aperture, the zygomaticomaxillary and nasomaxillary buttresses, and by the use of an arch bar. Since slower bone healing may be observed following palatoalveolar fractures, the occlusion must be observed for deviation throughout a full 16-week period even though early motion and soft diet are permitted. Removal of the plate and screws in the roof of the mouth is sometimes required and utilizes local anesthesia.

The prevalence of positive test results for Chlamydia trachomatis by direct smear for fluorescent antibodies in a south Texas family planning population.

Chlamydia trachomatis is a major human genital pathogen implicated as a leading cause of involuntary infertility in women. To assess the prevalence of results positive for C trachomatis by a direct immunofluorescent test in a family planning population, mass screening of all patients attending five urban family planning clinics was conducted for a two-month period. The objectives of this study were to assess the prevalence of positive C trachomatis test results in this population and to evaluate the commonly accepted demographic/behavioral risk factors reported in previous studies. A total of 2,761 subjects were tested using the MicroTrak collection kit. The subjects ranged in age from 12 to 69 years. The overall rate of positive test results was 10.5%. Significant associations between C trachomatis test results and the following variables were observed: race/ethnicity, age, marital status, existence of multiple partners and positive gonorrhea tests. Chlamydial infection was not significantly associated with income, pregnancy, current contraceptive method or age at first intercourse. While the results of the study indicated both agreement and disagreement with other clinical investigations, the fact that 10.5% of a largely asymptomatic population exhibited chlamydial infection has major implications for the management of women's reproductive health care.

Comparative radiographic study of human and animal long bone patterns.

The objective of this study was to test the hypothesis that certain radiographic features can be found to distinguish between human and animal long bone fragments, and therefore would be useful as an adjunct in forensic science identification. Using proposed radiographic criteria, 13 archeologists and 12 dentists were asked to identify 20 radiographic samples as representing human or animal bone. Results showed that archeologists correctly identified 86.8% of the samples, and dentists correctly identified 81.9%. Based on the results of this study, it was concluded that radiographic interpretation of long bone fragments may be a useful aid in a forensic science investigation of human and animal remains.

Principal components analysis of physical growth in savannah baboons.

Morphometric data collected from 118 male and 169 female savannah baboons (Papio cynocephalus anubis) aged between birth and 5.5 years were analyzed to describe the morphology and physical growth of this species. Measurements included weight, crown-rump length, triceps circumference, and skinfolds at the neck, subscapular, suprailiac, and triceps anatomical sites. Principal components analyses were applied to the data to provide multivariate assessments of morphological patterning among the variables. These analyses resulted in the extraction of two unrotated orthogonal components that accounted for 88% of the overall sample variation. The first component accounted for 77% of the variation and represents an axis of overall body size. The second component represents an axis of shape variation that contrasts body size with fat patterning, and was interpreted as a measure of body leanness. Individual component scores were computed for determining age, gender, and age-by-gender interaction effects. Both components were found to be age dependent for both genders. Males and females shared similar age patterning along the two components; however, gender differences did occur in patterning along the two components; however, gender differences did occur in respect to leanness. The multivariate measure of overall body size increased for both genders similarly with advancing age. Age patterning along the leanness component was described as a decrease from birth to 1 year, followed by an increase in leanness in older ages. Females had a delayed and significantly less intense increase in leanness relative to males.

Bilateral asymmetry of long arm bones and jugular foramen: implications for handedness.

The analysis of asymmetry of the arm long bones and of the cranial jugular foramen has been used to suggest handedness in humans. However, because of the unavailability of documented skeletal material, neither criterion has been systematically tested. If both criteria are associated with handedness, they should also be intercorrelated within individuals. Data were collected from skeletal material of 125 males and 57 females to test whether this intercorrelation exists. According to Chi-square analysis, no statistically significant association was identified. After examining several hypotheses, it was concluded that until further substantiation, neither criterion is related to handedness to a degree appropriate for forensic science identification from skeletal remains.