A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster.

Drosophila melanogaster has a rich repertoire of innate and learned behaviors. Its 100,000-neuron brain is a large but tractable target for comprehensive neural circuit mapping. Only electron microscopy (EM) enables complete, unbiased mapping of synaptic connectivity; however, the fly brain is too large for conventional EM. We developed a custom high-throughput EM platform and imaged the entire brain of an adult female fly at synaptic resolution. To validate the dataset, we traced brain-spanning circuitry involving the mushroom body (MB), which has been extensively studied for its role in learning. All inputs to Kenyon cells (KCs), the intrinsic neurons of the MB, were mapped, revealing a previously unknown cell type, postsynaptic partners of KC dendrites, and unexpected clustering of olfactory projection neurons. These reconstructions show that this freely available EM volume supports mapping of brain-spanning circuits, which will significantly accelerate Drosophila neuroscience. VIDEO ABSTRACT.

In vivo albumin labeling and lymphatic imaging.

The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid)-conjugated truncated Evans blue ((18)F-AlF-NEB) and Evans blue (EB) dye. After local injection, both (18)F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from (18)F-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of (18)F-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance.

Jejunal Diverticulosis: An Atypical Lead Point for Small Bowel Volvulus.

The occurrence of small intestinal diverticula is relatively infrequent compared to its counterpart in the large bowel. Duodenal diverticula exhibit a significantly higher prevalence within the small intestine compared to jejunoileal diverticula, with a ratio of five to one. The occurrence of jejunoileal diverticula exhibits considerable variability and has been documented to range from 0.5% to 2.3% in radiographic series, while autopsy studies have reported rates as high as 7%. We present the clinical details of a 65-year-old male patient who sought medical attention due to a constellation of symptoms, including abdominal pain, vomiting, and obstipation. After adequate resuscitation with IV fluids and preoperative preparation, the patient was transported to the operating room for an emergency exploratory laparotomy. Multiple jejunal diverticuli were identified in the proximal jejunum at the antimesenteric border, less than three feet from the duodenojejunal (DJ) junction. The terminal ileum was found to be 360° rotated counterclockwise around the small bowel mesentery, causing the small intestine to appear congested; however, after clockwise de-rotation, the small bowel regained its normal color. Adhesiolysis and small bowel decompression were performed, and the patient had an uneventful recovery.

Wunderlich Syndrome: A Seldom Presentation of a Relatively Ubiquitous Tumor.

Wunderlich syndrome (WS) is characterized by spontaneous renal or perinephric hemorrhage in the absence of known trauma. WS is much rarer than haemorrhage caused by iatrogenic or traumatic conditions. The classic WS presentation of Lenk's triad of acute onset flank pain, flank mass, and hypovolemic shock is seen in less than a quarter of patients. The majority of patients present with only isolated flank pain and are frequently imaged in the emergency department with an unenhanced computed tomography (CT). The underlying aetiology varies, with the majority of cases attributed to neoplasms, vascular disease, cystic renal disease, and anticoagulation. We hereby present a case of an 80-year-old female who presented with severe discomfort in her left flank for three days in the absence of trauma. The patient was brought in a state of hypovolemic shock. After a thorough evaluation, a diagnosis of WS secondary to angiomyolipoma was made, for which selective angioembolization of the left renal artery was performed. However, due to further deterioration, a left nephrectomy had to be performed. The patient had an uneventful recovery and showed no deterioration on follow-up. The treatment modalities are vivid depending on the hemodynamic status of the patient, ranging from conservative management to operative intervention, and should be tailored to the vital state on admission.

Ameloblastic fibroma: A case report.

Ameloblastic fibroma is a rare mixed odontogenic benign tumor that can occur in either mandible or maxilla but mostly it is found in posterior region of mandible. It can present either peripherally or centrally with a majority of the cases predominantly occurring in first two decades of life and mostly affects male patients. It is characterized by epithelial islands and cords submerged in ectomesenchyme that bear resemblance to the dental papilla and enamel organ but without actual hard tissue formation. Ameloblastic fibroma is a rare odontogenic tumor consisting of neoplastic epithelial and mesenchymal tissues. Recent reports have suggested that this lesion has the potential for high recurrence (18%) and greater chances of recurrent Ameloblastic fibroma transforming into Ameloblastic fibrosarcoma (45%). A 34-year-old male patient presented with pain and swelling in right mandibular posterior region. Intraorally expansion of buccal cortical plate with tenderness over swelling was present. Extraoral examination revealed facial asymmetry on right side. In view of imaging and clinical findings, provisional diagnosis of Odontogenic Keratocyst or Recurrent Ameloblastoma was considered. After obtaining informed consent and general systemic evaluation, the lesion was enucleated under general anesthesia and biopsied which confirmed the diagnosis of Ameloblastic fibroma. Ameloblastic fibroma is a mixed odontogenic tumor composed of odontogenic ectomesenchyme resembling dental papilla with epithelial strands and nests similar to the dental lamina and enamel organ, but with no dental hard tissue formation. Odontogenic tumors, Ameloblasts, Ameloblastoma, Jaw neoplasm.

Angiofibroma of the mandible: Rare sight for juvenile tumor.

Angiofibroma also called juvenile nasopharyngeal angiofibroma are tumors of adolescence and the commonest site is the nasopharynx. Extra nasopharyngeal sites include upper respiratory and digestive tracts, oral cavity, tonsils, larynx, trachea, and esophagus. Intraosseous angiofibroma is the rarest of a rare entity.

Role of Intra-articular Piroxicam in the Temporomandibular Joint After Arthrocentesis for Anterior Disc Displacement Without Reduction.

STUDY DESIGN: This is comparative experimental research to evaluate the role of piroxicam in the temporomandibular joint (TMJ) after arthrocentesis. OBJECTIVE: To evaluate the role of intra-articular piroxicam in the temporomandibular joint after arthrocentesis for anterior disc displacement without reduction. MATERIAL AND METHODS: Twenty-two individuals (twenty-two TMJs) were evaluated clinically and radiographically for the study, and then they were randomly assigned to one of two groups. As for group I, they were given arthrocentesis using Ringer's solution (100 ml). Group II received an intra-articular injection of 20 mg/mL of piroxicam (in 1 mL of Ringer's solution) after arthrocentesis (100 mL). The same individuals were assessed both before and after surgery to determine the degree to which their symptoms had improved. Patients were seen in the clinic once a week for the first month after surgery, then once a month for the next three months. RESULT:  Group II patients presented with better results when compared with Group I. CONCLUSION: It can be concluded that installing a 1 ml intra-articular injection of piroxicam at a concentration of 20 mg/ml after arthrocentesis improves the relief of symptoms, both qualitatively and quantitatively. Relief of TMJ symptoms reduced the anxiety in the patients as evaluated by the BAIS (Beck's Anxiety Inventory Scale) score.

The Role of 5-Fluorouracil in Preventing Recurrence After Enucleation of Odontogenic Keratocyst: A Case Report.

The odontogenic keratocyst (OKC) is known for its high recurrence rate and disputed treatment modalities. In this report, we review the literature elucidating the efficacy of 5-fluorouracil (5-FU) topical application for recurrent OKC, and discuss the management of an OKC with 5-FU after enucleation and a 12-month follow-up. A 38-year-old female patient with an aggressive OKC in the right mandible underwent surgical curettage followed by topical application of 5-FU. Regular follow-up examinations for 12 months (radiological evaluation at three, six, and 12-month intervals) showed no signs of recurrence, with complete resolution of the cystic lesion and gradual bone regeneration. New bone formation was identified in the radiographic follow-up.  This case demonstrates the potential efficacy of topical 5-FU as a promising treatment modality for OKC, warranting further research and validation. A novel and successful therapy for OKC is the topical application of 5-FU. After enucleation, topical application of 5-FU efficiently treats OKC, leading to normal bone healing and regeneration without any adverse local or systemic effects.

Platelet-Rich Fibrin-Enhanced Bone Healing Co-grafted With Either Hydroxyapatite and Beta Tricalcium Phosphate or Demineralized Freeze-Dried Bone in Small Maxillofacial Osseous Defects: A Clinical Comparison.

INTRODUCTION: This study was conducted to clinically compare a commercially available combination of 70:30 nanocrystalline hydroxyapatite (HA) and beta tricalcium phosphate (ßTCP) along with platelet-rich fibrin (PRF) with demineralized freeze-dried bone (DFDB) grafts along with PRF in small maxillofacial osseous defects. MATERIALS AND METHODS: Thirty patients with one osseous defect were randomly distributed into two groups of 15 each: Group A and Group B. Group A patients received HA+ßTCP+PRF while Group B received DFDB + PRF. Postoperative pain, swelling, wound dehiscence, and the presence or absence of infection were evaluated at various intervals up to seven postop days and compared between the two groups and within either group. A technetium 99m methylene diphosphonate (MDP 99mTc) scan was also done for a representative patient of either group at the end of three months to evaluate the fate of the graft. RESULTS: We found no significant difference between the two groups for any of our parameters. Significant improvements were noted for pain and swelling within either group at various intervals. The MDP 99mTc scan showed increased tracer uptake for the representing patient of either group. CONCLUSIONS: HA+ßTCP is more inexpensive than DFDB and more readily available and has no host incompatibility or infection potential, resulting in similar clinical postoperative states as DFDB when either is used with PRF.

Structured sampling of olfactory input by the fly mushroom body.

Associative memory formation and recall in the fruit fly Drosophila melanogaster is subserved by the mushroom body (MB). Upon arrival in the MB, sensory information undergoes a profound transformation from broadly tuned and stereotyped odorant responses in the olfactory projection neuron (PN) layer to narrowly tuned and nonstereotyped responses in the Kenyon cells (KCs). Theory and experiment suggest that this transformation is implemented by random connectivity between KCs and PNs. However, this hypothesis has been challenging to test, given the difficulty of mapping synaptic connections between large numbers of brain-spanning neurons. Here, we used a recent whole-brain electron microscopy volume of the adult fruit fly to map PN-to-KC connectivity at synaptic resolution. The PN-KC connectome revealed unexpected structure, with preponderantly food-responsive PN types converging at above-chance levels on downstream KCs. Axons of the overconvergent PN types tended to arborize near one another in the MB main calyx, making local KC dendrites more likely to receive input from those types. Overconvergent PN types preferentially co-arborize and connect with dendrites of αß and α'ß' KC subtypes. Computational simulation of the observed network showed degraded discrimination performance compared with a random network, except when all signal flowed through the overconvergent, primarily food-responsive PN types. Additional theory and experiment will be needed to fully characterize the impact of the observed non-random network structure on associative memory formation and recall.

Bilateral sagittal split osteotomy a versatile approach for correction of facial deformity: A review literature.

Poor facial cosmesis resultant from dysgnathias usually accounts for a range of these individuals' psychological and social problems. Disturbances of both esthetics and function are caused by jaw deformity and associated structures' deformity such as malocclusion. The correction of these deformities is one of the most challenging and intriguing aspects of maxillofacial surgery. Despite having become routine only relatively recently, rigid internal fixation has advanced rapidly, its results are consistent and predictable and thus, its knowledge applies in orthognathic surgery besides other areas of maxillofacial surgery. The bilateral sagittal split osteotomy (BSSO) is a common orthognathic procedure performed on the mandible. First described by Trauner and Obwegeser in 1957, modified by Dal Pont and refined by Epker, several modifications of the BSSO have been introduced aiming to enhance surgical convenience, minimize morbidity, and maximize stability. The aim of this article is to review the literature of this technique from the historical perspective and to present a standard operation technique.

2 mm Conventional Miniplates with Three-Dimensional Strut Plate in Mandibular Fractures.

AIM: The aim of this study was to compare 2 mm conventional miniplates with three-dimensional (3D) strut plates in the treatment of mandibular fractures treated in the Department of Oral and Maxillofacial Surgery of a college in India, during 2012-2015. MATERIALS AND METHODS: All 20 patients with mandible fracture requiring open reduction and internal fixation of the fracture were reported and reviewed in the Department of Oral and Maxillofacial Surgery of the same dental college in India, during 2012-2015. We classified the data according to the gender, age, etiology, fracture site, and method of treatment of the fractures. Fixation done in 10 patients with 2 mm conventional miniplates kept in Group I, while 10 patients with 3D strut miniplate system considered in Group II. RESULTS: Assessment of patient was done under the following parameters with follow-up at regular intervals at 2nd day postoperatively and at 1st, 3rd, and 6th weeks postoperatively: pain, swelling, infection, interincisal mouth opening in millimeters, paresthesia/anesthesia, mobility between fracture fragments, overall occlusion, need for any supplemental fixation, fate of implant, and complications. CONCLUSIONS: 3D titanium miniplates showed similar results when compared to standard titanium miniplates with advantages such as reduction in operative time, ease of placement, and cost-effective over the conventional plate system.

Label-free global serum proteomic profiling reveals novel celecoxib-modulated proteins in familial adenomatous polyposis patients.

Celecoxib, a selective inhibitor of cyclooxygenase-2 (Cox-2), was efficacious in clinical prevention trials of patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer. To identify as yet poorly defined molecular determinants of celecoxib efficacy, a multidimensional serum fractionation approach was used coupled with nanospray tandem mass spectrometry to perform label-free global proteomic profiling of serum samples from the FAP/celecoxib prevention trial. Subsequently, the application of an algorithm for large-scale biomarker discovery on comparative serum proteomic profiles of pre- and post-celecoxib treatment samples identified 83 potentially celecoxib-responsive proteins from various cellular compartments, biological processes and molecular functions. Celecoxib modulation of some of these proteins was confirmed in serum samples of FAP patients and colorectal cancer cell lines by Western blotting. Thus, using a shotgun procedure to rapidly identify important celecoxib-modulated proteins, this pilot study has uncovered novel systemic changes some of which are highly relevant for carcinogenesis and vascular biology. Validation of selected markers, especially those involved in key signaling networks and those considered molecular indicators of cardiovascular pathology, in larger celecoxib clinical trials is expected to provide insights into the molecular mechanisms of celecoxib and the efficacy/toxicity issues related to its use as a chemopreventive agent.

Clinical Relevance of Pretransplant Testing for Anti-Human Leukocyte Antigen Antibodies in Iraqi Renal Transplant Patients.

OBJECTIVES: The use of highly sensitive Luminex technology to assess the immunologic risk of renal transplant candidates have greatly added to the ability of stratifying patients and have paved the way to avoid hyperacute antibody-mediated rejection. Our aim was to understand how much the testing for pretransplant anti-HLA antibodies affects the decision for transplant and survival at 1 year posttransplant. MATERIALS AND METHODS: From January 2014 to June 2017, 336 transplant candidates were tested by complement-dependent cytotoxicity and by the Luminex platform for anti-HLA antibodies in our nephrology and renal transplant center (The Medical City, Baghdad, Iraq). All clinical and laboratory data were noted. Our program is a living-donor, blood group-compatible donor program. All transplant patients (sensitized or not) were followed for 1 year, and the Kaplan-Meier method was used to determine survival rate. RESULTS: Mean age of the study group was 34.07 ± 12.4 years. Of 336 transplant patients who were tested, there were 63 (18.75%) sensitized patients and 159 (47.35%) nonsensitized patients. Blood transfusion was the main cause of sensitization. Class I anti-HLA antibodies were detected in 54 of 63 sensitized patients (85.7%), and class II anti-HLA antibodies were detected in 39 of 63 sensitized patients (61.9%). Donor-specific antibodies were detected in 33/63 (52.3%). Thirteen sensitized patients (15.3%) underwent transplant. No incidences of hyperacute rejection were recorded. The 1-year survival of the nonsensitized patient group was 90%, whereas survival was 61.5% for the sensitized patient group. CONCLUSIONS: Pretransplant testing for anti-HLA antibodies is undoubtedly useful for assessment of patient risk, to facilitate decisions regarding patient and donor selection, and to plan treatment strategies. The 1-year survival for sensitized patient was lower than for nonsensitized patients. More knowledge, experience, technology advancements, and support are needed to improve the Iraqi practice of transplanting sensitized patients.

Altered gene expression profiles define pathways in colorectal cancer cell lines affected by celecoxib.

It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2-independent activities. In an attempt to better understand COX-2-independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2-positive and COX-2-deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies.

MTHFR genotype and colorectal adenoma recurrence: data from a double-blind placebo-controlled clinical trial.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. We assessed the association between two common MTHFR variants, 677C>T and 1298A>C, and adenoma recurrence in the context of a randomized double- blind clinical trial of aspirin use and folate supplementation. We used generalized linear regression to estimate risk ratios and 95% confidence intervals (95% CI) for recurrence, adjusting for age, sex, clinical center, follow-up time, and treatment status. Neither MTHFR polymorphism was associated with overall or advanced adenoma recurrence. Compared with those with two wild-type alleles, the relative risk for advanced adenoma was 0.75 (95% CI, 0.36-1.55) for the MTHFR 677 TT genotype and 1.16 (95% CI, 0.58-2.33) for the MTHFR 1298 CC genotype. The effect of folate supplementation on recurrence risk did not differ by genotype. Our findings indicate that the MTHFR genotype does not change adenoma risk in a manner similar to its effect on colorectal cancer, and does not modify the effect of folate supplementation on metachronous adenoma risk.

Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation.

BACKGROUND: Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas. METHODS: The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association. RESULTS: We found a borderline significant inverse association with plasma B(6) [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; P(trend) = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetrahydrofolate reductase -C677T and plasma B(2) on risk of all adenomas. CONCLUSION: Our results suggest that high levels of PLP and B(2) may protect against colorectal adenomas.

Protective effect of Cox-2 allelic variants on risk of colorectal adenoma development in African Americans.

BACKGROUND: Recent evidence indicates that single nucleotide polymorphisms (SNPs) in the Cox-2 gene may modulate the risk of colorectal adenoma development. PATIENTS AND METHODS: We explored possible associations between Cox-2 polymorphisms and risk of adenoma development in an African American case-control study comprising 72 cases of advanced adenomas and 146 polyp-free controls. An exhaustive approach of genotyping 13 haplotype-tagging SNPs (ht SNPs) distributed over the entire COX-2 gene was used. RESULTS: Statistically significant inverse associations were observed between the heterozygous genotypes at the 5229 G>T polymorphism in intron 5 [odds ratio (OR)=0.42; confidence interval (CI)=0.19-0.92; p=0.03] and at the 10935 A>G polymorphism in the 3' flanking region downstream from the poly A signals (OR=0.39; CI=0.18-0.83;p=0.01) and the risk for colorectal adenoma development. CONCLUSION: The data from our pilot study suggest that allelic variants of the COX-2 gene significantly influence the risk of adenoma development in the African American population.

The Modified Iliopubic Tract Repair-A Pain-Free Alternative.

Background The open preperitoneal repair offers the benefits of placing the mesh in the preferred position while avoiding the disadvantages of laparoscopic repair. Methods A total of 60 patients with bilateral inguinal hernias were randomized to undergo either the standard Lichtenstein meshplasty or the modified iliopubic tract repair in a teaching hospital. Outcomes measured were immediate postoperative pain, return to activity, and delayed neurological complications. Results Patients who underwent the iliopubic tract repair walked out of bed faster than the Lichtenstein group (6.3 hours vs 7.4 hours, p < 0.0001) and experienced significant lower pain as charted by visual analogue scale scores (3.28 vs 2.71 on day 1, 2.16 vs 1.71 on day 2, 1.92 vs 1.08 on day 3; p < 0.05). Delayed complications like chronic inguinal pain and numbness were not seen in the iliopubic tract group. However, this difference was not statistically significant ( p > 0.05). Conclusion The iliopubic tract repair offers an excellent alternative to the Lichtenstein meshplasty, and is associated with lower postoperative pain, earlier return to work, and lower delayed neurological complications.