EEC‐ and ADULT‐Associated TP63 Mutations Exhibit Functional Heterogeneity Toward P63 Responsive Sequences

TP63 germ‐line mutations are responsible for a group of human ectodermal dysplasia syndromes, underlining the key role of P63 in the development of ectoderm‐derived tissues. Here, we report the identification of two TP63 alleles, G134V (p.Gly173Val) and insR155 (p.Thr193_Tyr194insArg), associated to ADULT and EEC syndromes, respectively. These alleles, along with previously identified G134D (p.Gly173Asp) and R204W (p.Arg243Trp), were functionally characterized in yeast, studied in a mammalian cell line and modeled based on the crystal structure of the P63 DNA‐binding domain. Although the p.Arg243Trp mutant showed both complete loss of transactivation function and ability to interfere over wild‐type P63, the impact of p.Gly173Asp, p.Gly173Val, and p.Thr193_Tyr194insArg varied depending on the response element (RE) tested. Interestingly, p.Gly173Asp and p.Gly173Val mutants were characterized by a severe defect in transactivation along with interfering ability on two DN‐P63α‐specific REs derived from genes closely related to the clinical manifestations of the TP63‐associated syndromes, namely PERP and COL18A1. The modeling of the mutations supported the distinct functional effect of each mutant. The present results highlight the importance of integrating different functional endpoints that take in account the features of P63 proteins' target sequences to examine the impact of TP63 mutations and the associated clinical variability.     

Leiomyosarcoma of the inferior vena cava--a case report

This paper presents a patient successfully treated for leiomyosarcoma of the vena cava, with no recurrence or symptoms on an 8-year follow-up. A 56-year-old woman presented with chronic and progressive periumbilical and right upper abdominal pain. Physical examination and laboratory tests revealed no abnormalities. Computed tomography showed a high-density image inside the vena cava. Cavography showed a filling defect with complete occlusion of the vena cava involving the renal veins and greatly developed collateral circulation through lumbar veins. Laparotomy was performed and a large caval mass involving the renal veins was dissected and resected. Venous reconstruction was undertaken using a 19-mm bovine pericardium prosthesis (Labcor, MG-Brazil) interposed as a substitute to the vena cava, and the renal veins were anastomosed to the side of the graft. Pathologic examination confirmed a leiomyosarcoma with free surgical margins. The postoperative course was uneventful and the patient was discharged on postoperative day 8. The venous flow through the inferior vena became normal, as confirmed by later cavography. This paper presents a case of successfully managed leiomyosarcoma of the vena cava with a thorough review of the literature. The treatment of such patients and the use of bovine pericardium are also discussed.     

Lymph Node Retrieval after Preoperative Chemoradiotherapy for Rectal Cancer

Background

Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients.

Methods

An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained.

Results

On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P?P?=?0.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not.

Conclusions

Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.     

Prevention of hemorrhagic complications after dental extractions into open heart surgery patients under anticoagulant therapy: the use of leukocyte- and platelet-rich fibrin

Leukocyte- and platelet-rich fibrin (L-PRF) is a biomaterial commonly used in periodontology and implant dentistry to improve healing and tissue regeneration, particularly as filling material in alveolar sockets to regenerate bone for optimal dental implant placement. The objective of this work was to evaluate the use of L-PRF as a safe filling and hemostatic material after dental extractions (or avulsions) for the prevention of hemorrhagic complications in heart surgery patients without modification of the anticoagulant oral therapy. Fifty heart surgery patients under oral anticoagulant therapy who needed dental extractions were selected for the study. Patients were treated with L-PRF clots placed into 168 postextraction sockets without modification of anticoagulant therapy (mean international normalized ratio = 3.16 ± 0.39). Only 2 patients reported hemorrhagic complications (4%), all of which resolved a few hours after the surgery by compression and hemostatic topical agents. Ten patients (20%) showed mild bleeding, which spontaneously resolved or was resolved by minimal compression less than 2 hours after surgery. No case of delayed bleeding was reported. The remaining 38 patients (76%) showed an adequate hemostasis after the dental extractions. In all cases, no alveolitis or painful events were reported, soft tissue healing was quick, and wound closure was always complete at the time of suture removal one week after surgery. The proposed protocol is a reliable therapeutic option to avoid significant bleeding after dental extractions without the suspension of the continuous oral anticoagulant therapy in heart surgery patients. Other applications of the hemostatic and healing properties of L-PRF should be investigated in oral implantology.     

Characterization of a Parkinson’s disease rat model using an upgraded paraquat exposure paradigm

Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5‐fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α‐synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ‐based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration.     

Acute Amebic Appendicitis

Introduction Acute appendicitis of amebic origin is considered a rare cause of acute appendicitis. Methods The clinical notes for 4093 patients over the age of 16 who had undergone appendectomy were reviewed. Particular attention was paid to the histopathologic results, separating out those cases where trophozoites were seen in the appendix. These cases were considered to be of amebic origin. Results A total of 93 cases reported lesions suggestive of amebiasis (2.3%). This study analyzed 86 of these cases. Comparing the cases in this study against the cases of patients with acute appendicitis in general (excluding the cases of amebic origin), no differences were found in relation to the distribution or presentation according to sex or in the degree of inflammation of the appendix, the incidence of surgical wound infection, or general complications. By contrast, the study noted a statistically significant difference in the age at presentation: Acute appendicitis of amebic origin presents principally among those under 20 years of age and is accompanied by a higher frequency of fecal fistula (2.3%). Conclusions Acute appendicitis of amebic origin is not seen frequently, and in general it does not behave any differently from other cases of acute appendicitis, except in its earlier presentation and its greater incidence of fecal fistula. The condition is suspected clinically whenever a cecum of hard, “cardboard-like” consistency is discovered.     

Prevalence of odontogenic cysts and tumors associated with impacted third molars: A systematic review and meta-analysis

PurposeThis systematic review aimed to investigate the prevalence of odontogenic cysts and tumors associated with impacted third molars (ITM).MethodsOnly studies that performed histopathological diagnosis of lesions were eligible for inclusion. Five main electronic and three grey literature databases were searched. Risk of bias (RoB) of included articles was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.ResultsFrom 1,300 studies identified, 16 met the inclusion criteria. Seven studies were classified as high, seven as moderate, and two as low RoB. The prevalence of odontogenic cysts and tumors associated with ITM was 5.3% (95%CI: 3.1%–8.1%) of ITM. Odontogenic cysts in particular were found in 4.4% (95%CI: 2.5–6.8%) of the extracted ITM, whilst odontogenic tumors in 0.5% (95%CI: 0.2–0.9%). The dentigerous cyst was mentioned in eleven studies with a pooled prevalence of 2.1% (95%CI: 1.4–3.1%). The odontogenic keratocyst was cited by nine studies and had a prevalence of 0.5% (95%CI: 0.2–0.7%). The radicular cyst was mentioned only in three articles and the pooled prevalence was 4.7% (95%CI: 0.0–19.4%)ConclusionOdontogenic cysts and tumors were found in 5.3% of ITM extracted. The most common lesions were the radicular cyst, dentigerous cyst, and odontogenic keratocyst.     

The Chemical Protecting Group Concept Applied in Crosslinking of Natural Tissues with Glutaraldehyde Acetals

This work describes the results of the controlled crosslinking of collagen matrices by glutaraldehyde based on a double protection strategy, glutaraldehyde acetals and lysine protonation due to the acidic conditions of acetal formation. Materials crosslinked by this approach were characterized by thermal stability comparable to those obtained by conventional procedures with mechanical properties expected for bioprosthesis manufacture and with a higher stability toward collagenase hydrolysis. The integrity of the microfibrillar structure was confirmed by optical and scanning electronic microscopy. The results indicate that the glutaraldehyde acetals procedure may be of potential use for the crosslinking of bovine pericardium used in the manufacture of bioprosthetic devices. Advantages may be related to the production of materials with homogeneous crosslinking distributions, associated with better definition in the nature of the chemical link that they introduce, due to a better distribution of glutaraldehyde within the tissue matrix before the crosslinking reaction is allowed to occur. As a result, materials with improved biological and mechanical properties are expected.