Angiopoietin-2 is expressed in oral Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma (KS) persists today as a highly prevalent vascular cancer, often found in HIV patients. Studies have shown that angiopoietin 2 (Ang2), a pro-angiogenic protein, is involved in the pathogenesis of this tumor. However, expression of this protein has not been investigated in oral KS lesions. Thus, we aimed to investigate the expression of Ang2 in samples of oral KS. METHODS: Immunohistochemistry was used to evaluate Ang2 expression in 14 oral KS cases, with degrees of expression being analyzed in a semi-quantitative manner. In addition, clinical information such as age, gender, race, tumor location, size, color, and appearance, as well as HIV status, was collected and included in the analysis. RESULTS: All patients were white males, mostly HIV-positive, with a mean age of 40 years. Clinically, the lesions were dark red/blue/purple masses, ranging from 1 to 2.5 cm in diameter, found in various locations such as the tongue, palate, and gingiva. Expression of Ang2 was noted in 72% (10/14) of the samples. Of these, 10% showed weak expression, 60% moderate, and 30% strong expression. CONCLUSIONS: Our results indicate that Ang2 is expressed in oral KS and, consistent with results from previous studies, show that Ang2 may contribute to the pathogenesis of this lesion.

An evaluation of root resorption associated with the use of photobiomodulation during orthodontic treatment with clear aligners: a retrospective cohort pilot study.

OBJECTIVES: To evaluate the change in tooth root volume using cone-beam computed tomography (CBCT) in a group of patients treated concurrently with clear aligners and an adjunctive photobiomodulation (PBM) device. MATERIALS AND METHODS: This retrospective cohort pilot study included the records of 32 consecutively treated clear aligner patients (23 female, 9 male) from the private practice of one orthodontist. The PBM group (n = 16) used the device once per day for 5 minutes per arch and was compared with a matched control group (n = 16). A semiautomated segmentation technique was used to obtain tooth volume of anterior teeth from CBCT imaging prior to (T0) and during or immediately following (T1) orthodontic treatment with clear aligners. The change in root volume between time points was assessed. RESULTS: There was no statistically significant difference between the pre- and posttreatment root volumes of maxillary and mandibular anterior teeth, regardless of which intervention group the patient belonged to (P > .05). There was also no difference in the mean percentage change in root volume between clear aligner patients in this study who were treated with the PBM device compared with a matched control group (P > .05). CONCLUSIONS: Clear aligner patients in this study who changed their aligners every 3 to 5 days and used adjunctive photobiomodulation therapy did not experience clinically relevant orthodontically induced external root resorption. Due to the small sample size and measurement error in the root segmentation process, the results should be interpreted with caution.

Impact of low intensity pulsed ultrasound on volumetric root resorption of maxillary incisors in patients treated with clear aligner therapy: A retrospective study.

OBJECTIVE: The aim of this study was to evaluate the volumetric root resorption in maxillary incisors following clear aligner therapy (CAT) with low-intensity pulsed ultrasound (LIPUS), and compare the results to CAT alone. MATERIAL AND METHODS: This retrospective study evaluated pretreatment (T0) and post-treatment (T1) cone-beam computed tomography imaging of 42 adult patients. Twenty-one patients (14 females, 7 males, mean age= 38.1±12.96 years) were treated using CAT with LIPUS device, whereas the other twenty-one matching controls patients (15 females, 6 males, mean age= 35.6±11.7 years) were treated using CAT alone. Images were analyzed and a segmentation protocol was applied on the maxillary incisors. Each segmented tooth volume was exported as a surface mesh in the Visualization Toolkit (VTK) file format. The VTK files for all maxillary incisors were coded and corresponding teeth volumes from T0 and T1 were superimposed. Clipping the crown of each tooth was done, then measurements of root volumes and differences between groups were performed. Changes in root volumes were assessed (p<0.05). RESULTS: Root loss was evident in all teeth in both groups, but was significantly increased in all maxillary incisors of the control group (p<0.001) and in upper left central incisor of LIPUS group (p=0.009). When both groups were compared, there was statistically significant minimal volumetric root loss in LIPUS group (3.50-7.32 mm3), when compared to control group (11.48-12.95 mm3) (p<0.05). CONCLUSION: LIPUS group showed less volumetric root resorption compared to control group during the studied treatment time using clear aligners.

Physiological performance of a detergent decellularized heart valve implanted for 15 months in Vietnamese pigs: surgical procedure, follow-up, and explant inspection.

This study features the longest experimental follow-up for decellularized heart valves implanted in an animal model. Porcine aortic heart valves were decellularized according to a disclosed standardized method in which TRITON X-100 and sodium cholate (TRICOL) are used in succession, followed by a further treatment with the endonuclease Benzonase to completely remove the nucleic acid remnants. Experimental animals (n = 17), represented by Vietnamese pigs (VPs), received a decellularized aortic allograft as a substitute for the replacement of their right ventricular outflow tract. The surgical implantation of the TRICOL-treated aortic valve conduit was successful in 11 VPs, while perioperative or postoperative complications occurred in the remaining six animals. In the sham-operated group (n = 4), the native pulmonary root was excised and immediately reimplanted orthotopically in the same animal. Echocardiography demonstrated a satisfactory hemodynamic performance of the TRICOL-treated valves during follow-up as well as the absence of relevant leaflet alterations concerning thickness and motility or valve insufficiency. At explantation, macroscopic inspection of tissue-engineered heart valve conduits did not evidence calcifications and showed a decreased wall thickness, comparable to that of the reimplanted native pulmonary roots. Noteworthy, extended functional performance, recovery of DNA content, and active extracellular matrix precursor incorporation are apparently compatible with the properties of a living self-supporting substitute.

Treatment of severe post-traumatic bone defects with autologous stem cells loaded on allogeneic scaffolds.

Mesenchymal stem cells may differentiate into angiogenic and osteoprogenitor cells. The effectiveness of autologous pluripotent mesenchymal cells for treating bone defects has not been investigated in humans. We present a case series to evaluate the rationale of using nucleated cells from autologous bone marrow aspirates in the treatment of severe bone defects that failed to respond to traditional treatments. Ten adult patients (mean age, 49.6-years-old) with severe bone defects were included in this study. Lower limb bone defects were >or=5 cm3 in size, and upper limb defects .or=2 cm3. Before surgery, patients were tested for antibodies to common pathogens. Treatment consisted of bone allogeneic scaffold enriched with bone marrow nucleated cells harvested from the iliac crest and concentrated using an FDA-approved device. Postsurgery clinical and radiographic follow-up was performed at 1, 3, 6, and 12 months. To assess viability, morphology, and immunophenotype, bone marrow nucleated cells were cultured in vitro, tested for sterility, and assayed for the possible replication of adventitious (contaminating) viruses. In 9 of 10 patients, both clinical and radiographic healing of the bone defect along with bone graft integration were observed (mean time, 5.6 months); one patient failed to respond. No post-operative complications were observed. Bone marrow nucleated cells were enriched 4.49-fold by a single concentration step, and these enriched cells were free of microbial contamination. The immunophenotype of adherent cells was compatible with that of mesenchymal stem cells. We detected the replication of Epstein-Barr virus in 2/10 bone marrow cell cultures tested. Hepatitis B virus, cytomegalovirus, parvovirus B19, and endogenous retrovirus HERV-K replication were not detected. Overall, 470 to 1,150 million nucleated cells were grafted into each patient. This case series, with a mean follow-up of almost 2 years, demonstrates that an allogeneic bone scaffold enriched with concentrated autologous bone marrow cells obtained from the iliac crest provides orthopedic surgeons a novel option for treating important bone defects that are unresponsive to traditional therapies.

Penile lenghthening original technique using a pubo-cavernous spacer. Long term results from a series of over 200 patients.

INTRODUCTION: We report our long experience in the surgical treatment of patients requesting penile lengthening by suspensory ligament release and placement of a custom-made soft silicone pubo-cavernous spacer. The aim was to show that with this surgical technique the results obtained are maintained over time. It is crucial to achieve postoperative satisfaction of these patients who show fragility and self-esteem problems. METHODS: From 1999 to 2020, we treated 245 patients with congenital or acquired penile brevity. We carefully analysed the preoperative and postoperative (at 6, 12, 24 and 48 months) penile size of the patients to evaluate whether this technique could allow the long-term maintenance of aesthetic results. We also assessed preoperative erectile function and we focused on the psychological aspects to avoid surgery in patients with dysmorphophobia. This original technique involves the section of the suspensory ligament and the implantation of a silicone spacer between the pubic symphysis and the corpora cavernosa. This spacer is conformed to the patient anatomy and maintains the relationship between the anatomical structures unchanged over time. Sexual self-esteem and patient satisfaction were assessed with the APPSSI questionnaire. RESULTS: The mean increase in penile length was about 2.5 cm in flaccid state and 1.9 cm in stretched state. There were no injuries of the neurovascular bundle or urethra, and no erectile dysfunction was noted. These results persisted at 6, 12, 24 and 48 months without significant differences. Over 80% of patients stated that they were completely satisfied with the results obtained. This satisfaction remained stable along follow up. CONCLUSION: The section of the suspensory ligament and the implant of the soft silicone spacer provide real penis elongation with satisfactory results that persist over time. This technique avoids the frequent complication of short-term shortening due to the scar adhesions of the edges of the dissected ligament. The high aesthetic satisfaction of patients is stable at controls at 6, 12, 24 and 48 months.

Effect on quality of life of cisplatin added to single-agent chemotherapy as first-line treatment for elderly patients with advanced non-small cell lung cancer: Joint analysis of MILES-3 and MILES-4 randomised phase 3 trials.

OBJECTIVES: To evaluate the effect on quality of life (QOL) of the addition of cisplatin to single-agent chemotherapy in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC) enrolled in two parallel phase 3 trials, MILES-3 and MILES-4. PATIENTS AND METHODS: Advanced NSCLC pts, >70 years old, performance status (PS) 0-1, were eligible. Patients were randomly assigned to chemotherapy without or with cisplatin. EORTC QLQ C30 and LC13 questionnaires were planned at baseline, end of cycle 1 and end of cycle 2 in both trials and were used for joint QOL analysis. Trial-specific data including questionnaires at non-shared time-points were used for additional analyses. Intention-to-treat strategy was applied. Analyses were adjusted for baseline QOL, stage, performance status, gender, age, size of centre, trial, histotype and non-platinum companion drug. RESULTS: Overall, 458/531 pts (86%) answered baseline questionnaire and missing rates over treatment were slightly higher among patients receiving cisplatin. Mean change in sore mouth after cycle 2 was worse with cisplatin (P = 0.02). The size of differences between arms was in the small-medium range for peripheral neuropathy and alopecia (0.25 and 0.31 after one and 0.28 and 0.36 after two cycles, respectively) and for nausea/vomiting, sore mouth and dysphagia after two cycles (0.26, 0.38 and 0.25, respectively) always in the direction of worsening with cisplatin. Using a 10% change from baseline as clinically relevant threshold to categorize response, there was no significant difference between the arms. Time to deterioration of sore mouth and alopecia, with progression/death as competitive risk, was shorter with cisplatin (HR 1.72 95%CI 1.02-2.89, P = 0.04 and HR 1.84 95%CI 1.09-3.10, P = 0.02, respectively). CONCLUSION: The addition of cisplatin to single agent chemotherapy worsens sore mouth and alopecia and does not improve any QOL items in elderly patients with advanced NSCLC.

Impact of low intensity pulsed ultrasound on volumetric root resorption of maxillary incisors in patients treated with clear aligner therapy: A retrospective study

ABSTRACT Objective: The aim of this study was to evaluate the volumetric root resorption in maxillary incisors following clear aligner therapy (CAT) with low-intensity pulsed ultrasound (LIPUS), and compare the results to CAT alone. Material and Methods: This retrospective study evaluated pretreatment (T0) and post-treatment (T1) cone-beam computed tomography imaging of 42 adult patients. Twenty-one patients (14 females, 7 males, mean age= 38.1±12.96 years) were treated using CAT with LIPUS device, whereas the other twenty-one matching controls patients (15 females, 6 males, mean age= 35.6±11.7 years) were treated using CAT alone. Images were analyzed and a segmentation protocol was applied on the maxillary incisors. Each segmented tooth volume was exported as a surface mesh in the Visualization Toolkit (VTK) file format. The VTK files for all maxillary incisors were coded and corresponding teeth volumes from T0 and T1 were superimposed. Clipping the crown of each tooth was done, then measurements of root volumes and differences between groups were performed. Changes in root volumes were assessed (p<0.05). Results: Root loss was evident in all teeth in both groups, but was significantly increased in all maxillary incisors of the control group (p<0.001) and in upper left central incisor of LIPUS group (p=0.009). When both groups were compared, there was statistically significant minimal volumetric root loss in LIPUS group (3.50-7.32 mm3), when compared to control group (11.48-12.95 mm3) (p<0.05). Conclusion: LIPUS group showed less volumetric root resorption compared to control group during the studied treatment time using clear aligners.

RESUMO Objetivo: O objetivo deste estudo foi avaliar volumetricamente a reabsorção radicular em incisivos superiores após tratamento com alinhadores transparentes (CAT) com e sem uso adjuvante de ultrassom de baixa intensidade (LIPUS). Material e Métodos: Esse estudo retrospectivo avaliou imagens de tomografia computadorizada de feixe cônico pré-tratamento (T0) e pós-tratamento (T1) de 42 pacientes adultos: 21 pacientes (14 mulheres, 7 homens, idade média= 38,1±12,96 anos) foram tratados com CAT e LIPUS, enquanto os outros 21 pacientes controles correspondentes (15 mulheres, 6 homens, idade média= 35,6±11,7 anos) foram tratados apenas com CAT. As imagens foram analisadas e foi aplicado um protocolo de segmentação dos incisivos superiores. Os volumes de cada dente segmentado foram exportados como malhas de superfície, em arquivos no formato Visualization Toolkit (VTK). Os arquivos VTK de todos os incisivos superiores foram codificados e foram sobrepostos os volumes dos dentes correspondentes a T0 e T1. Foi realizada a clipagem da coroa de cada dente e, em seguida, foram realizadas medições dos volumes radiculares e comparadas as diferenças entre os grupos, avaliando-se as alterações nos volumes de raízes (p<0,05). Resultados: A perda radicular foi evidente em todos os dentes em ambos os grupos, mas foi significativamente maior em todos os incisivos superiores do grupo controle (p<0,001) e no incisivo central superior esquerdo do grupo LIPUS (p=0,009). Quando ambos os grupos foram comparados, houve perda volumétrica mínima estatisticamente significativa no grupo LIPUS (3,50-7,32 mm3), em comparação ao grupo controle (11,48-12,95 mm3) (p<0,05). Conclusão: O grupo LIPUS apresentou menor volume de reabsorção radicular, em comparação ao grupo controle, durante o tempo de tratamento estudado usando alinhadores transparentes.

Polyethylene Glycol-Poly-Lactide-co-Glycolide Block Copolymer-Based Nanoparticles as a Potential Tool for Off-Label Use of N-Acetylcysteine in the Treatment of Diastrophic Dysplasia.

Potential off-label therapeutic role of N-acetylcysteine (N-Ac) was recently demonstrated in the treatment of diastrophic dysplasia (DTD) using mutant mice; its main drawback is the rapid clearance from blood due to the liver metabolism. Our goal was to investigate the potential of polyethylene glycol polylactide-co-glycolide block copolymer (PLGA-PEG)-based nanoparticles (NPs) in order to improve in vivo biodistribution performances and N-Ac pharmacokinetic profile after subcutaneous administration in mice. Results suggest that N-Ac can be effectively loaded into NPs (about 99 µg/mg NPs) using a suitably optimized nanoprecipitation method. Thanks to the good physical characteristics (mean diameter <100 nm, zeta potential about -8 mV) NPs can reach skeletal tissue in particular femoral head and proximal tibia epiphysis at the sixth hour after injection, remaining in the tissues till 24 h. Furthermore, pharmacokinetic study revealed a sustained N-Ac concentration in plasma with a peak concentration of 2.48 ± 1.72 µM at the 24th hour after injection. Overall, results highlight the actual interest of N-Ac-loaded PLGA-PEG NPs as useful platform for N-Ac parenteral administration.

Deletion of pH Regulator pac-3 Affects Cellulase and Xylanase Activity during Sugarcane Bagasse Degradation by Neurospora crassa.

Microorganisms play a vital role in bioethanol production whose usage as fuel energy is increasing worldwide. The filamentous fungus Neurospora crassa synthesize and secrete the major enzymes involved in plant cell wall deconstruction. The production of cellulases and hemicellulases is known to be affected by the environmental pH; however, the regulatory mechanisms of this process are still poorly understood. In this study, we investigated the role of the pH regulator PAC-3 in N. crassa during their growth on sugarcane bagasse at different pH conditions. Our data indicate that secretion of cellulolytic enzymes is reduced in the mutant Δpac-3 at alkaline pH, whereas xylanases are positively regulated by PAC-3 in acidic (pH 5.0), neutral (pH 7.0), and alkaline (pH 10.0) medium. Gene expression profiles, evaluated by real-time qPCR, revealed that genes encoding cellulases and hemicellulases are also subject to PAC-3 control. Moreover, deletion of pac-3 affects the expression of transcription factor-encoding genes. Together, the results suggest that the regulation of holocellulase genes by PAC-3 can occur as directly as in indirect manner. Our study helps improve the understanding of holocellulolytic performance in response to PAC-3 and should thereby contribute to the better use of N. crassa in the biotechnology industry.

Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced non-small-cell lung cancer.

INTRODUCTION: The TORCH (Tarceva or Chemotherapy) trial randomized patients with advanced non-small-cell lung cancer to first-line erlotinib followed by second-line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed to test noninferiority in overall survival, was stopped at interim analysis because of inferior survival in the experimental arm. Quality of life (QoL), a secondary outcome, is reported here. METHODS: QoL was assessed at baseline and every 3 weeks during first-line, using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer specific module (LC13). Mean changes from baseline within arms were reported. QoL response and time-to-deterioration of QoL using a competing-risk approach were compared between treatment arms. RESULTS: Six hundred and thirty patients (83%) completed baseline questionnaires. Compliance was affected by differential treatment efficacy, but was similar between arms for patients without progression or death. Significant differences in QoL responses were observed favoring chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for vomiting, constipation, sore mouth, and alopecia. In the small subset of patients with EGFR-mutated tumors, all selected items (global QoL, physical functioning, cough, dyspnea and pain) improved, whereas worsening or no change was observed in wild-type patients. Improvement was particularly evident in the first-line erlotinib arm as for global QoL and physical functioning. CONCLUSIONS: QoL was impacted by differential toxicity and efficacy between arms. Functional domains and global QoL did not differ, although some symptoms were better controlled with chemotherapy in unselected non-small-cell lung cancer patients.