The Telemark Breast Score: a Valid Method for Evaluation of Outcome after Breast Surgery

Background: "Telemark Breast Score" (TBS) has been developed at Telemark Hospital in Norway for evaluation of results after breast surgery based on standardized patients' photographs taken as a part of daily routine. Its reliability has recently been tested and approved. The external validity of the TBS was assessed by matching its data against the internationally recognized Breast-Q (BQ) questionnaire as a further step to study the validity of this new tool. Methods: The ideal distribution of breast volume is 45% of the total volume above and 55% below the nipple, and a 40° slope line at the upper pole. TBS makes the evaluation of these parameters of breast aesthetics more explicit. The method has been tested on photographs from 31 patients operated on for breast cancer with the Deep Inferior Perforator Flap. The evaluation was done by an independent experienced plastic surgeon earlier participating in the test–retests. The external validity of TBS was investigated against domains 1 and 3 of the BQ reconstruction module. The concordance between ratings was analyzed. Results: Concordance between TBS items and BQ domain 1 items regarding patient satisfaction, and between TBS items and BQ domain 3 items regarding how the patient experienced the outcome of breast reconstruction was relatively high except for 6 comparisons where we could not statistically ensure that more pairs were concordant than discordant. A total of 178 comparisons appeared to be concordant. This means that for all other comparisons, there was a preponderance of pairs of concordant observations, which indicates that measurements from the 2 instruments follow each other. Conclusion: The present data indicate that the TBS can be recommended as a valid tool to professionals for assessment of the outcome after breast reconstruction.

http://ift.tt/2m03xgC

Zygomatico-maxillary Reconstruction with Computer-aided Manufacturing of a Free DCIA Osseous Flap and Intraoral Anastomoses

Summary: Craniomaxillofacial reconstruction using virtual surgical planning, computer-aided manufacturing, and new microsurgical techniques optimizes patient-specific and defect-directed reconstruction. A 3D customized free deep circumflex iliac artery (DCIA) flap with intraoral anastomoses was performed on a 23-year-old man with a posttraumatic right zygomatico-maxillary defect with failure of alloplastic implant reconstruction. An osseous iliac crest flap was sculpted based on a customized 3D model of the mirror image of the patient's unaffected side to allow for perfect fit to the zygomatico-maxillary defect. An intraoral dissection of the facial artery and vein was performed within the right cheek mucosa and allowed for end-to-end microvascular anastomoses. 3D preoperative planning and customized free DCIA osseous flap combined with an intraoral microsurgical technique provided restoration of facial esthetics and function without visible scars. In cases where zygomatico-malar reconstruction by alloplastic material fails, a customized free DCIA osseous flap can be designed by virtual surgical planning to restore facial appearance and function.

http://ift.tt/2m0caI7

Pedicled Retrograde Fibula Flap for Ankle Reconstruction after Oncologic Resection of the Distal Fibula

No abstract available

http://ift.tt/2m0egHX

A Modified Dual-plane Technique Using the Serratus Anterior Fascia in Primary Breast Augmentation

Background: Breast augmentations are commonly performed aesthetic surgical procedures. As the breast is a changeable structure, the ideal location of an implant would be a plane that can adjust to the dynamic changes of the breast. We present a modified dual-plane technique for breast augmentation using the fascia for thin patients. Methods: Between June 2014 and June 2015, 27 patients with small breasts underwent breast augmentation using the modified dual-plane technique. The average age was 29.4 years (range, 20–41 y). The mean body mass index was 18.9 kg/m2 (range, 17.6–20.4 kg/m2). Results: The mean size of the implant was 288.9 ml (range, 255–360 ml) on the right side and 281.6 ml (range, 255–360 ml) on the left side. All the patients returned to daily-life activities within 1 week. There have been no complications during minimum follow-up periods of 18 months. The mean follow-up was 25.6 months (range, 18–36 mo). Conclusions: Visible, palpable implants and rippling after breast augmentation with implants are relatively common problems. Our modified dual-plane technique with the serratus anterior fascia can reduce visible rippling and yields a natural-looking breast, especially in thin patients.

http://ift.tt/2m06lL0

Obesity-related Risk Factors in Implant-based Breast Reconstruction Using AlloDerm

With a population in which 70% of the patients were overweight or obese, we reviewed retrospectively 135 breasts of 70 consecutive patients who underwent implant-based immediate breast reconstruction using freeze-dried AlloDerm as the acellular dermal matrix. Several obesity-related parameters were evaluated to determine their possible correlation to early postoperative complications. We found that breast width and surface area of AlloDerm usage correlated with the development of infection and mastectomy skin flap necrosis. Increased breast width and size of AlloDerm matrix implanted were correlated with higher rates of both minor and significant skin necrosis and of cellulitis. Body mass index was correlated with the development of cellulitis and minor and major skin necrosis but not with seroma or reconstruction failure. Preexisting breast cup size correlated with the development of seroma but not the other complications. We observed no statistically significant association between reconstruction failure and any of the parameters reviewed, but this is likely due to the small number of failures in our data set (n = 10).

http://ift.tt/2m0199Q

Reconstruction of Wassel Type VI Radial Polydactyly with Triphalangeal Thumb Using an On-top Osteotomy

Background: The purpose of this study was to present a novel surgical technique using an on-top osteotomy and to assess the clinical and radiographic outcomes for the triphalangeal Wassel type VI thumb duplication patients. Methods: The surgical technique involves ablation of the radial thumb at distal one-third of the metacarpal, corresponding metacarpal osteotomy of the ulnar thumb, with amalgamation of 2 metacarpals and reconstruction of the ulnar thumb by a series of soft tissue procedures. Clinical and radiologic outcomes were evaluated by using the Japanese Society for Surgery of the Hand evaluation form at a minimum of 30 months. The size of the metacarpal was measured and compared to the opposite one to assess the growth of the thumb. Results: Five patients, including 4 males and 1 female, were observed for an average of 37 months. All amalgamated metacarpal showed bone union in 6 weeks after surgery and revealed growth with the age. The average length of the metacarpal was 86% of the opposite one at the final follow-up. Motion at the metacarpophalangeal and interphalangeal joints showed no restriction after surgery, and they reached excellent function for gripping and pinching. According to the JHHS scoring system, the results were excellent in 3 cases, good in 2. Conclusions: This novel surgical technique for the reconstruction of Wassel type VI radial polydactyly with triphalangeal shows encouraging results in both clinical and radiologic evaluations; meanwhile long-term results are under evaluation.

http://ift.tt/2m05hGE

The 4-flap Jester’s Hat Technique for Nipple Reduction

Summary: Macrothelia, or nipple hypertrophy, is a condition that may cause severe psychological distress to those who suffer from it. Although effective in their primary goal of reducing nipple diameter and projection, previously reported techniques in nipple reduction suffer from imperfect aesthetic outcomes with noticeable scarring patterns, anatomically anomalous shape, and a smoothing of the natural ruffles of the nipple. We propose a simple technique to nipple reduction that improves upon previous techniques and creates a more naturally appearing nipple. A 4-flap technique resembling a jester's hat is described whereby suture lines are concealed within the central nipple to recreate the naturally ruffled appearance of a native nipple. Four patients have undergone this technique at a single institution with 100% patient satisfaction and no postoperative complications. Nipple sensation was maintained in all patients postoperatively. A 4-flap nipple reduction technique is a viable alternative to previously described techniques, which may offer more anatomically congruent results.

http://ift.tt/2m02Uni

Multiple Recurrences in Aggressive Forms of Dupuytren’s Disease—Can Patients Benefit from Repeated Selective Fasciectomy?

Background: In Dupuytren's disease (DD), limited fasciectomy is the mainstay of surgical therapy in patients at risk of contractures and disease recurrences. New minimally invasive treatments such as injection of collagenase clostridium histolyticum have evolved as a common tool for the preliminary treatment of Dupuytren's contractures. However, recurrences and their therapy remain controversial. In this study, we evaluate the benefit of repeated limited fasciectomy in patients with aggressive forms of the disease and multiple recurrences of contractures. Methods: We evaluated the outcome of 16 patients undergoing limited fasciectomy 3 or more times on a single hand. Results: Postoperatively, 10 of 13 (76.9%) patients were satisfied with the clinical result after the last operation; 10 of 12 (83.3%) patients would choose to have their surgery repeated, if so needed. The mean improvement of proximal interphalangeal joint range of motion was 59.2 degrees (SD 26.8) and 86.2% (SD 19.9). There were no severe complications after treatment within the observed time period. Conclusions: Our findings demonstrate that patients with recurrence of contractures after multiple previous treatments in aggressive forms of DD can benefit from surgical intervention. In conclusion, repeated limited fasciectomy remains indicated in patients after previous surgeries with DD.

http://ift.tt/2m04tli

Anatomical Variation of Zygomatic Nerve Branches around Zygomaticus Major Muscle in Facelift

No abstract available

http://ift.tt/2m02U6M

Avoiding Facial Incisions with Midface Free Tissue Transfer

Background: We have adopted an intraoral microsurgical anastomosis to the facial vessels to eliminate the need for any visible facial incisions. Methods: Cadaveric dissection was used to demonstrate accessibility of the facial artery and vein through an intraoral approach. Additionally, 5 patients underwent free tissue transfer for reconstruction of major defects of the midface through an intraoral, transmucosal approach, obviating the need for visible skin incisions. Results: The pathology included palatal defects due to mucoepidermoid carcinoma and ischemic necrosis from cocaine abuse, maxillary defects secondary to fibrous dysplasia and avascular necrosis from traumatic blast injury, and a residual posttraumatic bony deformity of the zygoma. Reconstructions were performed with a free ulnar forearm flap, a free vastus lateralis muscle flap, a deep circumflex iliac artery myoosseous flap, a free fibula flap, and a deep circumflex iliac artery osseous flap, respectively. The facial artery and vein were used as recipient vessels for microvascular anastomosis for all cases. Mean follow-up was 12.2 months. All free tissue transfers were successful, and each patient had a satisfactory aesthetic outcome with no associated facial scars. Conclusion: This technique can be employed during reconstruction of an array of bony or soft-tissue midface deficits with minimal morbidity. This small series effectively demonstrates the varied pathologies and tissue deficiencies that can be successfully reconstructed with free tissue transfer using an entirely intraoral approach to the recipient facial vessels, resulting in no visible scars on the face and an improvement in the overall aesthetic outcome.

http://ift.tt/2lZRxfj

Resolution of Primary Lymphedema: A Case Report

Summary: Primary lymphedema is a rare, progressive disease that typically affects the lower extremity. The condition is not curable, and the limb enlarges over time because of subcutaneous fibroadipose deposition. We present a patient with clinical and radiographical evidence of resolution of primary lymphedema. This observation may provide greater insight into the pathophysiology of the disease.

http://ift.tt/2m06kqq

Radical Dissection of Greater Palatine Artery and Dynamic Reconstruction of Cleft Palate

Background: Restoration of proper anatomy and physiology is an integral part of cleft palate repair. The senior author has devised a new technique of radical release of greater palatine vessels, which helps in achieving tension-free closure of palatal cleft. In addition, release and transposition of palatal muscles is performed without the use of operative microscope, resulting in improved palatal function. This technique is applicable to all types of clefts of the palate and can be performed on adult patients as well. Materials and Methods: This is a retrospective case series of cleft palate repairs performed over a period of 3 years. Single-stage repair with modified Bardach's technique for complete cleft palate and von Langenbeck's technique for incomplete cleft palate with radical release of greater palatine vessels and levator complex retropositioning was performed. The outcome measures were closure of palatal defect and speech production. A follow-up of at least 6 months was completed in each patient. Results: A total of 1568 patients were included in the study. Their age ranged from 9 months to 54 years. The overall fistula rate was 6.1%. Improvement of speech was observed even in adult patients. Conclusions: Radical release of greater palatine artery and levator complex transposition can dramatically improve results of cleft palate repair. This technique helps in dynamic reconstruction of cleft palate and can be effectively applied in all age groups.

http://ift.tt/2m017Pg

A Comprehensive Approach to Lower Extremity Free-tissue Transfer

Background: The purpose of this study was to introduce a comprehensive approach to lower extremity free-tissue transfer and report the clinical outcome that has been achieved with this approach. Methods: The comprehensive approach developed by the author includes patient selection, flap selection, selection of the recipient vessels, flap dissection, flap preparation, microvascular anastomosis, flap inset, immediate postoperative care, intermediate postoperative care, and further follow-up care. Each part of this approach has its own special considerations. In an 8-year period, 28 consecutive lower extremity free-tissue transfers were performed in 28 patients by the author. The clinical outcomes were recorded based on the success of free-tissue transfer, any reoperations related to the revision of microvascular anastomosis, and any partial or total flap loss during an 8-year follow-up. Results: All 28 lower extremity free-tissue transfers were performed successfully. All patients were discharged home once they tolerated dangling. No reoperations were needed for revision of microvascular anastomosis. No total or partial flap loss was encountered. Overall success of free-tissue transfer to the lower extremity in this series was 100%. Conclusions: An ideal outcome of free-tissue transfer to the lower extremity can be accomplished with this comprehensive approach developed by the author. With good surgical judgment, adequate microsurgical skill, step-by-step intraoperative execution, and a protocol-driven clinical practice, the reconstructive surgeon should be able to improve his or her success for free-tissue transfer to the lower extremity.

http://ift.tt/2m0c43d

Application of Kuhnt–Szymanowski Procedure to Lower Eyelid Margin Defect after Tumor Resection

Background: Lower eyelid reconstruction after tumor removal is always challenging, and full-thickness defects beyond half of the eyelid length require a flap from a part other than the remaining lower eyelid, such as the temporal area or the cheek. Objective: We aimed to report our experience of applying Smith-modified Kuhnt–Szymanowski, one of the most popular procedures for paralytic ectropion, for reconstructing oblong full-thickness lower eyelid margin defect. Materials and Methods: We performed Smith-modified Kuhnt–Szymanowski on 5 cases of oblong full-thickness lower eyelid margin defect after skin cancer removal. The mean age of patients was 80.0 years. The horizontal widths of the defects ranged from half to two-thirds of the lower eyelid length and the vertical width ranged from 5 to 9 mm. Results: We obtained good functional and esthetic results in all cases. No patients developed ectropion or lower eyelid distortion, and all patients were satisfied with their results. Conclusions: We utilized the procedure for morphological revision as a reconstructive procedure for eyelid margin defect by considering the defect as a morphological deformity of the eyelid margin; thus, donor tissue was not required to fill the defect and we could accomplish the reconstruction simply, firmly, and less invasively.

http://ift.tt/2lZMNGy

Intradermal Infiltration of Local Anesthetic—Rapid and Bloodless Deepithelialization of the Breast Pedicle

Summary: Breast reduction is one of the most commonly performed plastic surgery procedures, and pedicle deepithelialization remains a time-consuming step of the operation. This is especially true when using an inferior pedicle. We present a novel technique of intradermal infiltration of the breast pedicle with local anesthetic to facilitate efficient, bloodless deepithelialization. The senior author uses a 20-ml syringe to inject 0.25% lidocaine and 1:400,000 epinephrine just beneath the epidermis of the breast pedicle to create a series of wheals. Approximately 20 ml of local anesthetic is used per pedicle. After injection of local anesthetic, the breast pedicle is deepithelialized in less than 3 minutes. The plane is bloodless, allowing improved visualization secondary to the epinephrine-induced hemostasis. The senior author has had only one case of nipple necrosis in 20 years of experience. Intradermal infiltration of local anesthetic with epinephrine hydrodissects between the epidermis and dermis and provides hemostasis to facilitate rapid deepithelialization.

http://ift.tt/2lZVQXU

Reconstruction of Through-and-through Oromandibular Defect: Comparison of Four Different Techniques

Background: Through-and-through oromandibular defects originate from surgical intervention of tumors of the oral cavity involving external skin, soft tissue, bone, and oral lining. Reconstruction of such composite defects is primarily achieved by 4 methods using distinct flaps in Chang Gung Memorial Hospital, including a single anterolateral thigh (ALT) flap, a single fibula flap, an osteomyocutaneous peroneal artery-based combined flap, and a combination of a fibular flap and an ALT flap, also known as a double flap. Methods: In this retrospective study, 41 patients with through-and-through oromandibular defects reconstructed in Chang Gung Memorial Hospital Linkou branch from July 2007 to June 2009 using either of the 4 flaps were evaluated. Patients were divided into 4 groups according to the choice of flap, and their surgical outcomes, immediate and late complications, and their general condition were studied. Group 1 included 12 patients reconstructed with a single ALT flap, whereas group 2 included 15 patients using fibular flaps. Group 3 included 8 patients with osteomyocutaneous peroneal artery-based combined flaps, and group 4 included 6 patients who underwent reconstruction with double flaps. Results: Among all statistical results, we found that none of the differences regarding either patient demography or surgical outcomes between groups were statistically significant, except for squamous cell carcinoma staging. Conclusions: Although the results were insignificant, trends within the data could be seen that support previous notions regarding each reconstruction method. For future studies, we strongly recommend a larger sample size.

http://ift.tt/2n01j5Z

Vertical PAP Flap: Simultaneous Longitudinal Profunda Artery Perforator Flaps for Bilateral Breast Reconstructions

No abstract available

http://ift.tt/2mZOTLs

Management of Toxic Epidermal Necrolysis with Plasmapheresis and Cyclosporine A: Our 10 Years’ Experience

Background: The management of toxic epidermal necrolysis (TEN) is controversial and there is no uniform strategy. Objective: To share our 10 years' experience in treating severe TEN with a novel protocol based on the association of cyclosporine A and plasmapheresis. Methods: In this case series, we retrospectively collected and assessed the 12 cases of severe TEN treated from 2005 to 2015 at the Burn Unit of the University of Bari Policlinico hospital. Results: Average body surface area was 77; average SCORETEN was 4.3. The 12 patients had been treated with culprit drug withdrawal, systemic corticosteroids, and/or cyclosporine A with no response. The protocol was successfully administered in all 12 cases. Average time to response from protocol start was 4.9 days. Average time to remission from protocol start was 22 days; average hospital stay at our unit was 24.8 days. Four patients developed severe complications; 1 patient died. No complications linked to the protocol therapeutic measures were observed. The relatively small number of cases given the rarity of the condition is a limitation of this report. Conclusion: Our protocol based on the association of cyclosporine A and plasmapheresis is safe and efficacious in treating severe TEN.

http://ift.tt/2n00lqm

Three-Dimensional Vision: Circumferential Nonsurgical Neck Rejuvenation.

No abstract available

http://ift.tt/2mH8FL7

Er: YAG Laser Ablation: An Adjuvant Treatment for Medically Resistant Pyoderma Gangrenosum.

No abstract available

http://ift.tt/2lZWq83

Benign Polypoid Epithelioid Schwannoma.

No abstract available

http://ift.tt/2mH4ajC

Toluidine Blue Supports Differentiation of Folliculocentric Basaloid Proliferation From Basal Cell Carcinoma on Frozen Sections in a Small Single-Practice Cohort.

No abstract available

http://ift.tt/2lZYixE

Nasopharyngeal Swab Applicator for Chemical Matricectomy.

No abstract available

http://ift.tt/2mHgDUA

Effectiveness and Safety of Surgical Excision in the Treatment of Digital Mucoid Cysts.

BACKGROUND: Digital mucoid cysts have a tendency for recurrence after operative intervention. Several procedures are in use. OBJECTIVE: Retrospective evaluation for effectiveness, safety and patient satisfaction by using a questionnaire after treatment for digital mucoid cysts with targeted surgical excision and closure by flap-design. MATERIALS AND METHODS: All patients treated with surgical excision for digital mucoid cysts at the Dermatology Department of the Ludwigshafen City Hospital between 2007 and 2011 were evaluated using a specially designed questionnaire. RESULTS: We evaluated 31 patients. The patient group consisted of 65% women, the median age was 61 years. Seventy-eight percent of patients with nail involvement had a marked improvement or complete resolution of this complaint after surgery. A few complications (e.g., redness, pain or hematoma) were observed after treatment, but no patients required oral antibiotics. Patient evaluation of cosmetic outcome revealed high satisfaction with the procedure, nevertheless recurrence of the digital mucoid cysts was observed in 22.5% of all cases. CONCLUSION: Surgical excision in treatment of digital mucoid cysts was shown to be effective and safe. However, possible advantages and disadvantages of this treatment option should be discussed with the patients before a decision on the kind of therapy is reached. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2m06lu9

Pulsed Dye Laser Therapy in the Treatment of Warts: A Review of the Literature.

BACKGROUND: Warts or verrucae vulgaris are common cutaneous infections with currently no definitive curative treatments available. OBJECTIVE: To determine the efficacy of pulsed dye laser (PDL) in the treatment of warts. MATERIALS AND METHODS: A literature search was performed using the PubMed and MEDLINE databases. A search using {(Wart[s], verruca or condylomata)} AND [(Pulsed dye laser)] was used. Forty-four articles were identified as relevant to this review. RESULTS: Simple warts were very responsive to PDL, being treated successfully in over 95% of patients. Facial and anogenital warts also demonstrated excellent outcomes. Recalcitrant warts, displayed significant variability in their response, ranging between 50% and 100% across all articles. The response rates seen in peripheral warts (involving the hands and feet) were also very variable, ranging between 48% and 95%. Recurrence rates at 4 months of follow-up were documented as 0% to 15%. Complications have been described as very few and rare, the main ones being topical discomfort and erythema. CONCLUSION: Pulsed dye laser is a safe and effective modality in the treatment of warts that can be applied to most body parts. Cost and availability remain a limitation to the use of PDL; however, this modality can be used when other more traditional and accessible treatments have failed. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2mH8L5C

Squamous Cell Carcinoma Arising Within an Accessory Tragus.

No abstract available

http://ift.tt/2m0blPv

Mixed-Methods Research in Nutrition and Dietetics

Publication date: Available online 8 March 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Jamie Zoellner, Jeffrey E. Harris
This work focuses on mixed-methods research (MMR) and is the 11th in a series exploring the importance of research design, statistical analysis, and epidemiologic methods as applied to nutrition and dietetics research. MMR research is an investigative technique that applies both quantitative and qualitative data. The purpose of this article is to define MMR; describe its history and nature; provide reasons for its use; describe and explain the six different MMR designs; describe sample selection; and provide guidance in data collection, analysis, and inference. MMR concepts are applied and integrated with nutrition-related scenarios in real-world research contexts and summary recommendations are provided.



http://ift.tt/2lEO8r1

A new mechanism shapes the naïve CD8+ T cell repertoire: The selection for full diversity

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Pedro Gonçalves, Marco Ferrarini, Carmen Molina-Paris, Grant Lythe, Florence Vasseur, Annik Lim, Benedita Rocha, Orly Azogui
During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clone sizes. Indeed with these approaches, identical TCRs may correspond to different cells expressing the same receptor, or to several amplicons from the same T cell. We here overcame this limitation by evaluating TCRB expression in individual naïve CD8⁺ T cells. Of the 2269 Tcrb sequences we obtained from 13 mice, 99% were unique. Mathematical analysis of this data showed that the average number of naïve peripheral CD8⁺ T cells expressing the same TCRB is 1.1 cell. Since TCRA co-expression studies could only increase repertoire diversity, these results reveal that the number of naïve T cells with unique TCRs approaches the number of naïve cells. Since thymocytes undergo multiple rounds of divisions after TCRB rearrangement; and 3–5% of thymocytes survive thymic selection events; the number of cells expressing the same TCRB was expected to be much higher. Thus, these results suggest a new repertoire selection mechanism, which strongly selects for full TCRB diversity.



http://ift.tt/2mH01MH

Versatile carboxyl-terminus of capsid protein of porcine circovirus type 2 were recognized by monoclonal antibodies with pluripotency of binding

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Ling-Chu Hung, Ivan-Chen Cheng
We designed the peptide (C3) mimetic carboxyl-terminus (Cterminus) of capsid protein of porcine circovirus type 2b (PCV2b-1A/1B) inducing humoral immunity and generating hybridomas. The positive reactivity of the mAbs to PCV2 capsid protein was demonstrated by Western blot assay. Those mAbs also showed positive signals on PCV2b infected swine lymphocytes by indirect immunofluorescence staining. The mAb 1H3 bound to three minimal linear epitopes (P62, DPPLNP; P67, DPPLNPK; P73, LKDPPLKP), which was located at Cterminus of the capsid protein of PCV2b-1A/1B, PCV2b-1C, and PCV2a-2A respectively. The mAbs 3B2 bound to only one minimal linear epitopes (P59, KDPPLNP). The mAbs 6B8 bound to two minimal linear epitopes (P59 and P67). Our data demonstrate the core motif (P62) within the P59 could be recognized by mAbs (3B2 and 6B8) in the free status by liquid phase blocking immunoassay (LPBI) but not be recognized by these mAbs in the fixed form on the plate by indirect ELISA (iELISA). However, the P73 could be recognized by mAb 1H3 by iELISA but no inhibition of the interactive binding of C3 and mAb 1H3 by LPBI. This study also indicated that IgM mAbs and defective Ig mAb have broad binding, moderate specificity and low affinity. This study confirm that mAbs have pluripotency of binding. It might be a phenomenon of antibody response to Cterminus of capsid protein of PCV2b.



http://ift.tt/2mk5kPz

Ionic tethering contributes to the conformational stability and function of complement C3b

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Andrés López-Perrote, Reed E.S. Harrison, Marta Subías, Martín Alcorlo, Santiago Rodríguez de Córdoba, Dimitrios Morikis, Oscar Llorca
C3b, the central component of the alternative pathway (AP) of the complement system, coexists as a mixture of conformations in solution. These conformational changes can affect interactions with other proteins and complement regulators. Here we combine a computational model for electrostatic interactions within C3b with molecular imaging to study the conformation of C3b. The computational analysis shows that the TED domain in C3b is tethered ionically to the macroglobulin (MG) ring. Monovalent counterion concentration affects the magnitude of electrostatic forces anchoring the TED domain to the rest of the C3b molecule in a thermodynamic model. This is confirmed by observing NaCl concentration dependent conformational changes using single molecule electron microscopy (EM). We show that the displacement of the TED domain is compatible with C3b binding to Factor B (FB), suggesting that the regulation of the C3bBb convertase could be affected by conditions that promote movement in the TED domain. Our molecular model also predicts mutations that could alter the positioning of the TED domain, including the common R102G polymorphism, a risk variant for developing age-related macular degeneration. The common C3b isoform, C3bS, and the risk isoform, C3bF, show distinct energetic barriers to displacement in the TED that are related to a network of electrostatic interactions at the interface of the TED and MG-ring domains of C3b. These computational predictions agree with experimental evidence that shows differences in conformation observed in C3b isoforms purified from homozygous donors. Altogether, we reveal an ionic, reversible attachment of the TED domain to the MG ring that may influence complement regulation in some mutations and polymorphisms of C3b.



http://ift.tt/2mGVI42

Nab2 maintains thymus cellularity with aging and stress

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): K.Taraszka Hastings, Diana Elizalde, Leela Muppana, Sarah Levine, Christy M. Kamel, Wendy M. Ingram, Jennifer T. Kirkpatrick, Chengcheng Hu, Matthew P. Rausch, Amelia L. Gallitano
Thymic cellularity is influenced by a variety of biological and environmental factors, such as age and stress; however, little is known about the molecular genetic mechanisms that regulate this process. Immediate early genes of the Early growth response (Egr) family have critical roles in immune function and response to environmental stress. The transcription factors, Egr1, Egr2 and Egr3, play roles in the thymus and in peripheral T-cell activation. Nab2, which binds Egrs 1, 2, and 3 as a co-regulator of transcription, also regulates peripheral T-cell activation. However, a role for Nab2 in the thymus has not been reported. Using Nab2-deficient (KO) mice we found that male Nab2KO mice have reduced thymus size and decreased numbers of thymocytes, compared with age-matched wildtype (WT) mice. Furthermore, the number of thymocytes in Nab2KO males decreases more rapidly with age. This effect is sex-dependent as female Nab2KO mice show neither reduced thymocyte numbers nor accelerated thymocyte loss with age, compared to female WT littermates. Since stress induces expression of Nab2 and the Egrs, we examined whether loss of Nab2 alters stress-induced decrease in thymic cellularity. Restraint stress induced a significant decrease in thymic cellularity in Nab2KO and WT mice, with significant changes in the thymocyte subset populations only in the Nab2KO mice. Stress reduced the percentage of DP cells by half and increased the percentage of CD4SP and CD8SP cells by roughly three-fold in Nab2KO mice. These findings indicate a requirement for Nab2 in maintaining thymocyte number in male mice with age and in response to stress.



http://ift.tt/2mjSwJ5

Preliminary study of an oral vaccine against infectious hematopoietic necrosis virus using improved yeast surface display technology

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Jing-Zhuang Zhao, Li-Ming Xu, Miao Liu, Yong-Sheng Cao, Scott E. LaPatra, Jia-Sheng Yin, Hong-Bai Liu, Tong-Yan Lu
Infectious hematopoietic necrosis virus (IHNV) is a common pathogen that causes severe disease in the salmonid aquaculture industry. Because oral vaccines induce more efficient mucosal immunity than parenteral immunization, an oral vaccine was developed with an improved yeast cell surface display technology to induce an immune response to IHNV. The oral yeast vaccine, designated EBY100/pYD1-bi-G, was delivered orally to rainbow trout (Oncorhynchus mykiss) on days 1 and 32, and the nonspecific and specific immune responses were measured 50days after the first vaccination. In the hindgut, spleen, and head kidney, the expression of IFN-1 and Mx-1 was significantly upregulated after oral vaccination with EBY100/pYD1-bi-G, and the highest expression of IFN-1 and Mx-1 was observed in the spleen (7.5-fold higher than the control group) and head kidney (3.9-fold higher than the control group), respectively. Several markers of the adaptive immune response (IgM, IgT, CD4, and CD8) were also significantly upregulated, and the highest expression of these markers was observed in the hindgut, suggesting that the mucosal immune response was successfully induced by oral vaccination with EBY100/pYD1-bi-G. Sera from the orally vaccinated rainbow trout showed higher anti-IHNV neutralizing antibody titers (antibody titer 81±4) than the control sera (antibody titer 7±3), and the relative percentage survival after IHNV challenge was 45.8% compared with 2% in the control group. Although the protection afforded by this orally delivered vaccine was lower than that of a DNA vaccine (83%–98%), it is a promising candidate vaccine with which to protect larval fish against IHNV, which are most susceptible to the virus and difficult to inject with a DNA vaccine.



http://ift.tt/2mGOFIs

Is estrogen exposure a protective factor for pancreatic neuroendocrine tumors in female multiple endocrine neoplasia syndrome type 1 patients?

Abstract

Objective

Pancreatic neuroendocrine tumors (PNETs) are the most common cause of death in multiple endocrine neoplasia type 1 (MEN1) patients. Women have been shown to have improved survival, which may suggest a possible protective effect of female sex hormones. The aim of this study was to evaluate the relationship between estrogen exposure and PNET tumorigenesis, tumor growth, and survival in female MEN1 patients with these tumors.

Design

We performed a retrospective chart review of the existing MEN1 database in our institution. Detailed information about female patients' menstrual and reproductive history, and PNET clinicopathologic characteristics was collected. Questionnaires regarding estrogen exposure were used to collect information that was missing in the database.

Patients

Of 293 confirmed MEN1 cases, 141 women met the inclusion criteria.

Measurements

We used measures of cumulative estrogen exposure time (CEET), parity, live birth pregnancies, and bilateral oophorectomy to estimate estrogen exposure.

Results

There was no significant association between CEET and time to PNET diagnosis (hazard ratio=0.966, P=0.380). For the correlation between estrogen exposure and PNET type, size, numbers, distant metastasis, lymph node metastasis, lymphovascular invasion, AJCC (American Joint Committee on Cancer) stage, and overall survival, only CEET was significantly correlated with PNET size (P= 0.043).

Conclusions

In female MEN1 patients, estrogen exposure may inhibit PNET growth. A demonstrable protective effect against PNET tumorigenesis, tumor growth, and survival of patients with these tumors may require a larger cohort.

This article is protected by copyright. All rights reserved.

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Hashimoto's thyroiditis: Relative recurrence risk ratio and implications for screening of first degree relatives

Abstract

Context

The relative recurrence risk ratio (λ_R) for Hashimoto's thyroiditis (HT) has not been widely studied. The age at which thyroid function evaluation should be initiated for relatives of HT patients remains unclear.

Objective

To study λ_R and age-related prevalence of HT in first degree relatives of HT patients.

Methods

First degree relatives (n=861) of 264 HT patients were evaluated for goitre, thyroid function tests, thyroid antibodies (TAb) and urinary iodide concentration (UIC). HT was defined as TAb positivity and hypothyroidism (subclinical/overt). λ_R was calculated as {number of index patients whose relatives (of particular subtype) had HT/number of index patients having relatives of same subtype}÷ population prevalence of HT (5.1%). The age-related prevalence of HT was studied using Kaplan–Meier method.

Results

861 relatives (205 parents, 336 siblings, 320 off-spring) participated in the study. 38.3% were TAb positive. The prevalence of HT was 16.7% (22.9% in parents, 19.6% in siblings, 9.6% in offspring). TAb positivity (48.3% vs. 33.1%) and HT (23.5% vs. 13.6%) were significantly more common in the goitrous group (n=267) vs non goitrous group. The median UIC for the study population was 182.5 μg/L. Computed λ_R was 9.1 for any one relative being affected, 5.9 for parents, 6.3 for siblings, and 3.1 for offspring. The prevalence of HT increased with age and exceeded the adult population prevalence of 5.1% at 20 years in females and 27 years in males.

Conclusions

Relatives of HT patients have a 9 fold increased risk for developing HT as compared to the general population. The risk of developing HT exceeds that of the general population at 20 years in females and 27 years in males.

This article is protected by copyright. All rights reserved.

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Features of papillary thyroid microcarcinoma associated with lateral cervical lymph node metastasis

Abstract

Objectives

Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis with an indolent disease course. However, some PTMCs have an aggressive course with lateral cervical lymph node (LCLN) metastasis or distant metastasis. This study aimed to evaluate the preoperative features of PTMC associated with LCLN metastasis.

Design and Patients

This retrospective cohort study with a nested, matched case-control design included 199 PTMC patients with LCLN metastasis at initial surgery (N1b group) and 196 PTMC patients without any LN metastasis or persistent disease (N0 NED group) as controls; primary tumour sizes were matched.

Results

Compared with the N0 NED group, the N1b group was younger (< 50 years) and more likely to be male (P = 0.002 and P = 0.003, respectively). On preoperative neck ultrasonography (US), N1b group PTMCs were more commonly associated with a location in the upper lobes of the thyroid, or in the subcapsular area and microcalcifications than N0 NED group PTMCs (all P <0.001). An increase in the number of these features was significantly associated with a higher risk of LCLN metastasis (P < 0.001). Evaluation of the clinical and preoperative US characteristics of 26 patients with confirmed LCLN recurrence after initial treatment of clinical N0 PTMCs revealed that the distribution of the number of suspicious features in these patients was similar to that of the N1b group.

Conclusions

PTMCs in young (<50 years) or male patients, with an upper lobe or subcapsular location, and with microcalcification have a higher risk of LCLN metastasis. Individualized management according to the number of these suspicious features may be needed for small thyroid nodules.

This article is protected by copyright. All rights reserved.

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Does Patient Reluctance Towards Exposure and Psychologists’ Attitudes about Evidence Based Practice Influence Treatment Recommendations for Panic Disorder? An Experimental Investigation

Publication date: Available online 6 March 2017
Source:Journal of Anxiety Disorders
Author(s): Nikolaos Kazantzis, Frank M. Dattilio, Davide Farchione
This study examined the effects of patient reluctance towards exposure on practitioners' subsequent treatment recommendations. Participants (N=236) were doctoral level psychologists who received a vignette of a patient with panic disorder, which either did (experimental group) or did not (control group) mention patient reluctance towards exposure. Evidence Based Practice (EBP) attitudes were also assessed and taken into account. A significant main effect of reluctance, averaged across all levels of EBP attitudes, and theoretical orientations was obtained (OR=2.85, 95% CI=[1.51, 5.39], p=0.001, RR=1.46), with controls 1.46 times more likely to recommend exposure. A significant main effect of EBP attitudes was also obtained (p <0.001). The odds of recommending exposure increased by 11% with each increase of positive EBP attitudes, across both levels of patient reluctance and theoretical orientation.



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Pivotal role of median eminence tanycytes for hypothalamic function and neurogenesis

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Karine Rizzoti, Robin Lovell-Badge
Along with the sub-ventricular zone of the forebrain lateral ventricles and the sub-granular zone of the dentate gyrus in the hippocampus, the hypothalamus has recently emerged as a third gliogenic and neurogenic niche in the central nervous system. The hypothalamus is the main regulator of body homeostasis because it centralizes peripheral information to regulate crucial physiological functions through the pituitary gland and the autonomic nervous system. Its ability to sense signals originating outside the brain relies on its exposure to blood-born molecules through the median eminence, which is localized outside the blood brain barrier. Within the hypothalamus, a population of specialized radial glial cells, the tanycytes, control exposure to blood-born signals by acting both as sensors and regulators of the hypothalamic input and output. In addition, lineage-tracing experiments have recently revealed that tanycytes represent a population of hypothalamic stem cells, defining them as a pivotal cell type within the hypothalamus. Hypothalamic neurogenesis has moreover been shown to have an important role in feeding control and energy metabolism, which challenges previous knowledge and offers new therapeutic options.



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Regulation of pituitary stem cells by epithelial to mesenchymal transition events and signaling pathways

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Leonard Y.M. Cheung, Shannon W. Davis, Michelle L. Brinkmeier, Sally A. Camper, María Inés Pérez-Millán
The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. The adult anterior pituitary responds to physiological challenge by mobilizing the SOX2-expressing progenitor pool and producing additional hormone-producing cells. Knowledge of the role of signaling pathways and extracellular matrix components in these processes may lead to improvements in the efficiency of differentiation of embryonic stem cells or induced pluripotent stem cells into hormone producing cells in vitro. Advances in our basic understanding of pituitary stem cell regulation and differentiation may lead to improved diagnosis and treatment for patients with hypopituitarism.



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Stem cells and their role in pituitary tumorigenesis

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Gabriela Carreno, Jose Mario Gonzalez-Meljem, Scott Haston, Juan Pedro Martinez-Barbera
The presence of adult pituitary stem cells (PSCs) has been described in murine systems by comprehensive cellular profiling and genetic lineage tracing experiments. PSCs are thought to maintain multipotent capacity throughout life and give rise to all hormone-producing cell lineages, playing a role in pituitary gland homeostasis. Additionally, PSCs have been proposed to play a role in pituitary tumorigenesis, in both adenomas and adamantinomatous craniopharyngiomas. In this manuscript, we discuss the different approaches used to demonstrate the presence of PSCs in the murine adult pituitary, from marker analyses to genetic tracing. In addition, we review the published literature suggesting the existence of tumor stem cells in mouse and human pituitary tumors. Finally, we discuss the potential role of PSCs in pituitary tumorigenesis in the context of current models of carcinogenesis and present evidence showing that in contrast to pituitary adenoma, which follows a classical cancer stem cell paradigm, a novel mechanism has been revealed for paracrine, non-cell autonomous tumor initiation in adamantinomatous craniopharyngioma, a benign but clinically aggressive pediatric tumor.



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Regenerative therapy for hypothyroidism: Mechanisms and possibilities

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Anthony N. Hollenberg, Jinyoung Choi, Maria Serra, Darrell N. Kotton
The ability to derive functional thyroid follicular cells from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) would provide potential therapeutic benefit for patients with congenital or post-surgical hypothyroidism. Furthermore, understanding the process by which thyroid follicular cells develop will also provide great insight into the key steps that regulate the development of other tissues derived from endoderm. Here we review the advances in our understanding of the process of thyroid follicular cell development including the creation of two models that have allowed for the rescue of hypothyroid mouse recipients through the transplantation of thyroid follicular cells derived from mouse ESCs. Rapid progress in the field suggests that the same success should be achievable with human ESCs or iPSCs in the near future. Additionally, the availability of ESC or iPSC-derived thyroid follicular cell models will provide ideal systems to explore how genetic mutations, drugs or illness impact thyroid function in a cell-autonomous fashion.



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Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Morgan K. Penny, Isabella Finco, Gary D. Hammer
The adrenal cortex is a dynamic tissue responsible for the synthesis of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens in humans. Advances have been made in understanding the role of adrenocortical stem/progenitor cell populations in cortex homeostasis and self-renewal. Recently, large molecular profiling studies of adrenocortical carcinoma (ACC) have given insights into proteins and signaling pathways involved in normal tissue homeostasis that become dysregulated in cancer. These data provide an impetus to examine the cellular pathways implicated in adrenocortical disease and study connections, or lack thereof, between adrenal homeostasis and tumorigenesis, with a particular focus on stem and progenitor cell pathways. In this review, we discuss evidence for stem/progenitor cells in the adrenal cortex, proteins and signaling pathways that may regulate these cells, and the role these proteins play in pathologic and neoplastic conditions. In turn, we also examine common perturbations in adrenocortical tumors (ACT) and how these proteins and pathways may be involved in adrenal homeostasis.



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Future perspectives in adult stem cell turnover: Implications for endocrine physiology and disease

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Clara V. Alvarez, Fernando Oroz-Gonjar, Montserrat Garcia-Lavandeira




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Leydig progenitor cells in fetal testis

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Yuichi Shima, Ken-ichirou Morohashi
Testicular Leydig cells play pivotal roles in masculinization of organisms by producing androgens. At least two distinct Leydig cell populations sequentially emerge in the mammalian testis. Leydig cells in the fetal testis (fetal Leydig cells) appear just after initial sex differentiation and induce masculinization of male fetuses. Although there has been a debate on the fate of fetal Leydig cells in the postnatal testis, it has been generally believed that fetal Leydig cells regress and are completely replaced by another Leydig cell population, adult Leydig cells. Recent studies revealed that gene expression patterns are different between fetal and adult Leydig cells and that the androgens produced in fetal Leydig cells are different from those in adult Leydig cells in mice. Although these results suggested that fetal and adult Leydig cells have distinct origins, several recent studies of mouse models support the hypothesis that fetal and adult Leydig cells arise from a common progenitor pool. In this review, we first provide an overview of previous knowledge, mainly from mouse studies, focusing on the cellular origins of fetal Leydig cells and the regulatory mechanisms underlying fetal Leydig cell differentiation. In addition, we will briefly discuss the functional differences of fetal Leydig cells between human and rodents. We will also discuss recent studies with mouse models that give clues for understanding how the progenitor cells in the fetal testis are subsequently destined to become fetal or adult Leydig cells.



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Leydig cell stem cells: Identification, proliferation and differentiation

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Haolin Chen, Yiyan Wang, Renshan Ge, Barry R. Zirkin
Adult Leydig cells develop from undifferentiated mesenchymal-like stem cells (stem Leydig cells, SLCs) present in the interstitial compartment of the early postnatal testis. Putative SLCs also have been identified in peritubular and perivascular locations of the adult testis. The latter cells, which normally are quiescent, are capable of regenerating new Leydig cells upon the loss of the adult cells. Recent studies have identified several protein markers to identify these cells, including nestin, PDGFRα, COUP-TFII, CD51 and CD90. We have shown that the proliferation of the SLCs is stimulated by DHH, FGF2, PDGFBB, activin and PDGFAA. Suppression of proliferation occurred with TGFβ, androgen and PKA signaling. The differentiation of the SLCs into testosterone-producing Leydig cells was found to be regulated positively by DHH (Desert hedgehog), lithium-induced signaling and activin; and negatively by TGFβ, PDGFBB, FGF2, Notch and Wnt signaling. DHH, by itself, was found to induce SLC differentiation into LH-responsive steroidogenic cells, suggesting that DHH plays a critical role in the commitment of SLC into the Leydig lineage. These studies, taken together, address the function and regulation of low turnover stem cells in a complex, adult organ, and also have potential application to the treatment of androgen deficiency.



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Ovarian regeneration: The potential for stem cell contribution in the postnatal ovary to sustained endocrine function

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Alisha M. Truman, Jonathan L. Tilly, Dori C. Woods
The endocrine function of the ovary is dependent upon the ovarian follicle, which on a cellular basis consists of an oocyte surrounded by adjacent somatic cells responsible for generating sex steroid hormones and maintenance of hormonal stasis with the hypothalamic-pituitary axis. As females age, both fertility and the endocrine function of the ovary decline due to waning follicle numbers as well as aging-related cellular dysfunction. Although there is currently no cure for ovarian failure and endocrine disruption, recent advances in ovarian biology centered on ovarian stem cell and progenitor cell populations have brought the prospects of cell- or tissue-based therapeutic strategies closer to fruition. Herein, we review the relative contributions of ovarian stem cells to ovarian function during the reproductive lifespan, and postulate steps toward the development of ovarian stem cell-based approaches to advance fertility treatments, and also importantly to provide a physiological long-term means of endocrine support.



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Pancreatic β-cell regeneration: Facultative or dedicated progenitors?

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Solomon Afelik, Meritxell Rovira
The adult pancreas is only capable of limited regeneration. Unlike highly regenerative tissues such as the skin, intestinal crypts and hematopoietic system, no dedicated adult stem cells or stem cell niche have so far been identified within the adult pancreas. New β cells have been shown to form in the adult pancreas, in response to high physiological demand or experimental β-cell ablation, mostly by replication of existing β cells. The possibility that new β cells are formed from other sources is currently a point of major controversy. Under particular injury conditions, fully differentiated pancreatic duct and acinar cells have been shown to dedifferentiate into a progenitor-like state, however the extent, to which ductal, acinar or other endocrine cells contribute to restoring pancreatic β-cell mass remains to be resolved. In this review we focus on regenerative events in the pancreas with emphasis on the restoration of β-cell mass. We present an overview of regenerative responses noted within the different pancreatic lineages, following injury. We also highlight the intrinsic plasticity of the adult pancreas that allows for inter-conversion of fully differentiated pancreatic lineages through manipulation of few genes or growth factors. Taken together, evidence from a number of studies suggest that differentiated pancreatic lineages could act as facultative progenitor cells, but the extent to which these contribute to β-cell regeneration in vivo is still a matter of contention.



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The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Chelsea Hepler, Rana K. Gupta
The rising incidence of obesity and associated metabolic diseases has increased the urgency in understanding all aspects of adipose tissue biology. This includes the function of adipocytes, how adipose tissue expands in obesity, and how expanded adipose tissues in adults can impact physiology. Here, we highlight the growing appreciation for the importance of de novo adipocyte differentiation to adipose tissue expansion in adult humans and animals. We detail recent efforts to identify adipose precursor populations that contribute to the physiological postnatal recruitment of white, brown, and beige adipocytes in mice, and summarize new data that reveal the complexity of adipose tissue development in vivo.



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Aging, metabolism and stem cells: Spotlight on muscle stem cells

Publication date: 15 April 2017
Source:Molecular and Cellular Endocrinology, Volume 445
Author(s): Laura García-Prat, Pura Muñoz-Cánoves
All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population.



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Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen

Publication date: Available online 7 March 2017
Source:Molecular and Cellular Endocrinology
Author(s): R.J. Watters, R.J. Hartmaier, H.U. Osmanbeyoglu, R.M. Gillihan, J. Rae, L. Liao, K. Chen, W. Li, X. Lu, S. Oesterreich
Steroid receptor coactivator-1 (SRC-1), a well-studied coactivator of estrogen receptor (ER), is known to play an important and functional role in the development and maintenance of bone tissue. Previous reports suggest SRC-1 maintains bone mineral density primarily through its interaction with ER. Here we demonstrate that SRC-1 can also affect bone development independent of estrogen signaling as ovariectomized SRC-1 knockout (SRC-1 KO) mouse had decreased bone mineral density. To identify estrogen-independent SRC-1 target genes in osteoblastogenesis, we undertook an integrated analysis utilizing ChIP-Seq and mRNA microarray in transformed osteoblast-like U2OS-ERα cells. We identified critical osteoblast differentiation genes regulated by SRC-1, but not by estrogen including alkaline phosphatase and osteocalcin. Ex vivo primary culture of osteoblasts from SRC-1 wild-type and KO mice confirmed the role of SRC-1 in osteoblastogenesis, associated with altered ALPL levels. Together, these data indicate that SRC-1 can impact osteoblast function in an ER-independent manner.



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Treatment of gestational diabetes mellitus with Myo-Inositol: analyzing the cutting edge starting from a peculiar case

OBJECTIVE: The robust data about Myo-Inositol (Myo-Ins) safety profile and effectiveness opened a new scenario for the treatment and prevention of Gestational Diabetes Mellitus (GDM). We report our experience about a case of GDM successfully treated with Myo-Ins.

PATIENTS AND METHODS: An overweight 29-year-old Caucasian pregnant woman, nulliparous, affected by GDM, according to the National Institute for Health and Care Excellence (NICE) Guideline. After diagnosis, the patient underwent regular glycemia checks: mean fasting blood glucose value was 103.63 ± 1.46 mg/dl, whereas 1-hour and 2-hours after-meal values were 122.74 ± 11.14 mg/dl and 110.74 ± 10.70 mg/dl, respectively. We decided to prescribe a low-calorie diet and oral treatment with 4 g of Myo-Ins, 3 times per day for 3 weeks.

RESULTS: After the treatment, mean fasting value was 90.74 ± 5.30 mg/dl, whereas 1-hour after and 2-hours after-meal values were 108.11 ± 6.05 mg/dl and 101.21 ± 4.78 mg/dl, respectively.

DISCUSSION: We reported a significant decrease of glycemia in a faster and steady way at fasting, 1-hour and 2-hours after-meal post oral treatment with 4 g of Myo-Ins 3 times per day, in a patient affected by GDM.

CONCLUSIONS: On the one hand, we could confirm the safety profile of the molecule also at this high dosage, free from any side effects; on the other hand, our experience highlighted the faster glucose-lowering effect due to a higher dose of Myo-Ins. This outcome may open a new scenario in the treatment of GDM.

L'articolo Treatment of gestational diabetes mellitus with Myo-Inositol: analyzing the cutting edge starting from a peculiar case sembra essere il primo su European Review.

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Myo-inositol and selenium reduce the risk of developing overt hypothyroidism in patients with autoimmune thyroiditis

OBJECTIVE: The beneficial effects obtained by myo-inositol in association with seleno-methionine in patients affected by subclinical hypothyroidism have been recently demonstrated. Here, we evaluate the immune-modulating effect of myo-inositol in association with seleno-methionine in patients with euthyroid autoimmune thyroiditis (AT).

PATIENTS AND METHODS: Twenty-one consecutive Caucasian patients with newly diagnosed euthyroid chronic AT were evaluated. All subjects were treated with myo-inositol in association with selenium (600 mg/83 mg) tablets, twice per day, for six months. A complete thyroid assessment was done before the treatment, and after six months.

RESULTS: After the treatment thyroid-stimulating hormone (TSH) levels significantly declined with respect to basal values, overall in patients with an initial TSH value in the high normal range (2.1<TSH<4.0), suggesting that the combined treatment can reduce the risk of a progression to hypothyroidism in subjects with autoimmune thyroid diseases (AITD). We found that after the treatment antithyroid autoantibodies levels declined. Moreover, the immune-modulatory effect was first confirmed by the fact that after the treatment CXCL10 levels declined, too.

CONCLUSIONS: We first show an immune-modulatory effect of myo-inositol in association with seleno-methionine in patients with euthyroid AT. Further studies are needed to extend the observations in a large population, to evaluate the effect on the quality of life, and to study the mechanism of the effect on chemokines.

L'articolo Myo-inositol and selenium reduce the risk of developing overt hypothyroidism in patients with autoimmune thyroiditis sembra essere il primo su European Review.

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Myo-Inositol plus selenium supplementation restores euthyroid state in Hashimoto’s patients with subclinical hypothyroidism

OBJECTIVE: Clinical evidence suggests that oral supplementation with myo-inositol (MI) and selenium (Se) is useful in the treatment of autoimmune thyroiditis. The purpose of this study was to highlight the positive response of Hashimoto's patients with subclinical hypothyroidism (SH) treated with MI and Se (MI-Se) in restoring a normal thyroid function.

PATIENTS AND METHODS: A total of 168 patients with Hashimoto's thyroiditis (HT) having Thyroid Stimulating Hormone (TSH) levels between 3 and 6 µIU/ml were randomized into 2 groups: one receiving MI-Se and the other one Se alone.

RESULTS: TSH, anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) levels were significantly decreased in patients treated with combined MI-Se after six months of treatment. Also, a significant free serum T4 increase was observed in MI-Se group, along with an amelioration of patients' quality of life.

CONCLUSIONS: The administration of MI-Se is significantly effective in decreasing TSH, TPOAb and TgAb levels, as well as in enhancing thyroid hormones and personal wellbeing. Such treatment restored euthyroidism in patients diagnosed with autoimmune thyroiditis.

L'articolo Myo-Inositol plus selenium supplementation restores euthyroid state in Hashimoto's patients with subclinical hypothyroidism sembra essere il primo su European Review.

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Atezolizumab and Bevacizumab in Rare Solid Tumors

Conditions:   Malignant Neoplasms of Digestive Organs;   Malignant Neoplasms of Lip Oral Cavity and Pharynx;   Malignant Neoplasms of Mesothelial and Soft Tissue;   Malignant Neoplasms of Respiratory and Intrathoracic Organs
Interventions:   Drug: Atezolizumab;   Drug: Bevacizumab;   Behavioral: Phone Call
Sponsors:   M.D. Anderson Cancer Center;   Genentech, Inc.
Not yet recruiting - verified March 2017

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The therapeutic effects of Periploca forrestii Schltr. Stem extracts on collagen-induced arthritis by inhibiting the activation of Src/NF-κB signaling pathway in rats

Publication date: Available online 7 March 2017
Source:Journal of Ethnopharmacology
Author(s): Lei Chen, Jinsong Li, Xuan Ke, Wei Qu, Jie Zhang, Feng Feng, Wenyuan Liu
Ethnopharmacological relevance:Periploca forrestii Schltr. is a classical traditional Chinese medicine (TCM) called Heilonggu (HLG) in China. According to the theory of TCM, it possesses the efficacy of eliminating wind and removing dampness. In clinical practice, it is commonly used for the treatment of rheumatoid arthritis. The present work aimed to evaluate the anti-rheumatism activity of HLG ethanol extract and reveal the underlying molecular mechanism by employing an animal model of collagen-induced rheumatoid arthritis (CIA) in rats.Materials and methods:The CIA was induced in male Sprague–Dawley rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant (CFA) at the base of tail. The rats received oral administration of HLG (200 and 400mg/kg) from day 1, with the treatment lasting for 28 days. A variety of indicators were measured for evaluation of anti-rheumatism effect, including paw swelling, arthritis scores, and histopathological changes. Furthermore, the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as cyclooxygenase-2 (COX-2), nuclear factor NF-κB p65 and Src kinase in joint synovial tissues were detected to explore the possible mechanisms.Results:The administration of HLG significantly restored type II collagen-induced arthritis in rats as evidenced by decrease in paw swelling and inflammatory factors in serum. Meanwhile, this treatment also notably reduced NF-κB p65 and COX-2 expression. Surprisingly, the activity of Src kinase was also inhibited demonstrated by downregulation of phosphorylated Src.Conclusion:Our results revealed that HLG possessed observable therapeutic action on collagen-induced arthritis by inhibiting the activation of Src and nuclear translocation of NF-κB in rats. HLG may serve as a potential candidate for the management of patients with RA.

Graphical abstract

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IFC (Journal of Ethnopharmacology)

Publication date: 6 March 2017
Source:Journal of Ethnopharmacology, Volume 199





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AKT-targeted anti-inflammatory activity of the methanol extract of Chrysanthemum indicum var. albescens

Publication date: 6 April 2017
Source:Journal of Ethnopharmacology, Volume 201
Author(s): Woo Seok Yang, Donghyun Kim, Young-Su Yi, Ji Hye Kim, Hye Yoon Jeong, Kyeonghwan Hwang, Jong-Hoon Kim, Junseong Park, Jae Youl Cho
Ethnopharmacological relevanceWild chrysanthemum (Chrysanthemum indicum) is one of well-known medicinal plants traditionally used in Korea and China. As a variant of wild chrysanthemum, white wild chrysanthemum (Chrysanthemum indicum var. albescens) is also ethnopharmacologically applied to treat various symptoms such as inflammatory diseases.Aim of studyAlthough the anti-inflammatory activity of Chrysanthemum indicum has been reported, the anti-inflammatory activity and underlying molecular mechanism of white wild chrysanthemum are poorly understood.Materials and methodsThe effects of Chrysanthemum indicum var. albescens methanol extract (Civ-ME) on the production of inflammatory mediators, expression of pro-inflammatory genes, cell viability, and the activities of intracellular signaling molecules and transcription factors were investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.ResultsCiv-ME suppressed the production of both nitric oxide (NO) and prostaglandin E2 (PGE2) without cytotoxicity in LPS-stimulated RAW264.7 cells. Civ-ME was found to reduce the mRNA levels of inflammatory genes such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α and reduced NF-κB-mediated transcriptional activation. Civ-ME inhibited the nuclear translocation of NF-κB (p65 and p50), and its upstream signaling composed of IκBα and IKKα/β. An NF-κB luciferase reporter gene assay and an in vitro kinase assay confirmed that AKT1 and AKT2 might be direct pharmacological targets of Civ-ME. In addition, luteolin was identified by HPLC analysis as the main active pharmacological components of Civ-ME.ConclusionCiv-ME exerts an anti-inflammatory effect by targeting AKT1 and AKT2 in the NF-κB signaling pathway in macrophage-mediated inflammatory responses.

Graphical abstract

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Anthelmintic effect of Psidium guajava and Tagetes erecta on wild-type and Levamisole-resistant Caenorhabditis elegans strains

Publication date: Available online 7 March 2017
Source:Journal of Ethnopharmacology
Author(s): Denia M. Piña-Vazquez, Zyanya Mayoral-Peña, Maricela Gómez-Sánchez, Luis A. Salazar-Olivo, Fausto Arellano-Carbajal
Ethnopharmacological relevancePsidium guajava and Tagetes erecta have been used traditionally to treat gastrointestinal parasites, but their active metabolites and mechanisms of action remain largely unknown.Aim of the studyTo evaluate the anthelmintic potential of Psidium guajava and Tagetes erecta extracts on Levamisole-sensitive and Levamisole-resistant strains of the model nematode Caenorhabditis elegans.Materials and MethodsAqueous extracts of Psidium guajava (PGE) and Tagetes erecta (TEE) were assayed on locomotion and egg-laying behaviors of the wild-type (N2) and Levamisole-resistant (CB193) strains of Caenorhabditis elegans.ResultsBoth extracts paralyzed wild-type and Levamisole-resistant nematodes in a dose-dependent manner. In wild-type worms, TEE 25mg/mL induced a 75% paralysis after 8h of treatment and PGE 25mg/mL induced a 100% paralysis after 4h of treatment. PGE exerted a similar paralyzing effect on N2 wild-type and CB193 Levamisole-resistant worms, while TEE only partially paralyzed CB193 worms. TEE 25mg/mL decreased N2 egg-laying by 65% with respect to the untreated control, while PGE did it by 40%.ConclusionsPsidium guajava leaves and Tagetes erecta flower-heads possess hydrosoluble compounds that block the motility of Caenorhabditis elegans by a mechanism different to that of the anthelmintic drug Levamisole. Effects are also observable on oviposition, which was diminished in the wild-type worms. The strong anthelmintic effects in crude extracts of these plants warrants future work to identify their active compounds and to elucidate their molecular mechanisms of action.

Graphical abstract

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Pharmacokinetics of Perfluorobutane after Intra-venous Bolus Injection of Sonazoid in Healthy Chinese Volunteers

Publication date: Available online 7 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Pengfei Li, Susan Hoppmann, Ping Du, Huiling Li, Paul M. Evans, Siver A. Moestue, Weiyue Yu, Fang Dong, Hongchuan Liu, Lihong Liu
Sonazoid is an ultrasound contrast agent based on microbubbles (MB) containing perfluorobutane (PFB) gas. Sonazoid is approved in Japan, Korea and Norway for contrast-enhanced ultrasonography of focal liver lesions and focal breast lesions (Japan only). The objective of this study was to determine the pharmacokinetics (PKs) and safety of Sonazoid in Chinese healthy volunteers (HVs) and to evaluate the potential for ethnic differences in PKs between Chinese and Caucasian HVs. Sonazoid was administered as an intra-venous bolus injection at the clinical dose of 0.12 μL or 0.60 μL MB/kg body weight to two groups of eight Chinese HVs. Expired air and blood samples were collected and analyzed using a validated gas chromatographic tandem mass spectrometry method, and the main PK parameters were calculated. The highest PFB concentrations in blood were observed shortly after intra-venous administration of Sonazoid, and elimination of PFB was rapid. In the 0.12 μL MB/kg body weight cohort, PFB concentrations above the limit of quantification were observed for only 10 to 15 min post-injection. In the 0.60 μL MB/kg body weight cohort, PFB concentrations above the limit of quantification were observed for 60 min post-injection, and the shape of the elimination curve suggested a biphasic elimination profile. The maximum observed concentration (Cmax) values of PFB in blood were 2.3 ± 1.1 and 19.1 ± 9.2 ng/g for the 0.12 and 0.60 μL MB/kg body weight dose groups (mean ± standard deviation). Area under the curve values were 10.1 ± 2.7 and 90.1 ± 38.3 ng × min/g for the 0.12 and 0.60 μL MB/kg body weight dose groups. Cmax values of PFB in exhaled air were 0.35 ± 0.2 and 2.4 ± 0.7 ng/mL for the 0.12 and 0.60 μL MB/kg body weight dose groups. Assessment of laboratory parameters, vital signs, oxygen saturation and electrocardiograms revealed no changes indicative of a concern. The PK profile and safety data generated in the Chinese HVs were comparable to previous data for Caucasian HVs.



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Whole-Breast Ultrasound for Breast Screening and Archiving

Publication date: Available online 7 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Chiun-Sheng Huang, Ya-Wen Yang, Rong-Tai Chen, Chung-Ming Lo, Chao Lo, Ching-Fen Cheng, Chao-Shuan Lee, Ruey-Feng Chang
The incidence of breast cancer is increasing worldwide, reinforcing the importance of breast screening. Conventional hand-held ultrasound (HHUS) for breast screening is efficient and relatively easy to perform; however, it lacks systematic recording and localization. This study investigated an electromagnetic tracking-based whole-breast ultrasound (WBUS) system to facilitate the use of HHUS for breast screening. One-hundred nine breast masses were collected, and the detection of suspicious breast lesions was compared between the WBUS system, HHUS and a commercial automated breast ultrasound (ABUS) system. The positioning error between WBUS and ABUS (1.39 ± 0.68 cm) was significantly smaller than that between HHUS and ABUS (1.62 ± 0.91 cm, p = 0.014) and HHUS and WBUS (1.63 ± 0.9 cm, p = 0.024). WBUS is a practical clinical tool for breast screening that can be used instead of the often unavailable and costly ABUS.



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Dosimetric impact of contouring and needle reconstruction uncertainties in US-, CT- and MRI-based high-dose-rate prostate brachytherapy treatment planning

Publication date: Available online 8 March 2017
Source:Radiotherapy and Oncology
Author(s): Susanne Rylander, Simon Buus, Erik M. Pedersen, Lise Bentzen, Kari Tanderup
Background and purposeThe purpose was to evaluate the dosimetric impact of target contouring and needle reconstruction uncertainties in an US-, CT- and MRI-based HDR prostate BT treatment planning.Material and methodsUS, CT, and MR images were acquired post-needle insertion in 22 HDR-BT procedures for 11 consecutive patients. Dose plans were simulated for an US-, CT- and MRI-based HDR-BT treatment planning procedure. Planning uncertainties in US- and CT-based plans were evaluated using MRI-based planning as reference. Target (CTVProstate) was re-contoured on MRI. Dose results were expressed in total equivalent dose given in 2Gy fractionation dose for EBRT (46Gy) plus 2 HDR-BT fractions.ResultsUncertainties in US- and CT-based planning caused the planned CTVProstate-D90% to decrease with a mean of 2.9±5.0Gy (p=0.03) and 2.9±2.9Gy (p=0.001), respectively. The intra-observer contouring variation on MRI resulted in a mean variation of 1.6±1.5Gy in CTVProstate-D90%. Reconstruction uncertainties on US resulted in a dose variation of±3Gy to the urethra, whereas data for CT were not available for this.ConclusionsUncertainties related to contouring and reconstruction in US- and CT-based HDR-BT treatment plans resulted in a systematic overestimation of the prescribed target dose. Inter-modality uncertainties (US and CT versus MR) were larger than MR intra-observer uncertainties.



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Planning study for Merkel cell carcinoma based on the relapse pattern

Publication date: Available online 8 March 2017
Source:Radiotherapy and Oncology
Author(s): Ulrike Hoeller, Tina Schubert, Thomas Mueller, Volker Budach, Pirus Ghadjar, Winfried Brenner, Wolf Kuschke
PurposeTo develop a technique for radiation (RT) of in-transit path ways (IT) in Merkel cell carcinoma.MethodIn the planning study, IT were ink-marked on the skin during sentinel lymphscintigraphy and wire-marked in planning-CT. Pre- and post-operative planning-CTs were acquired. The clinical target volume (CTV) included tumor bed plus safety margin, IT and draining nodes, the planning volume (PTV) the CTV plus 0.5–1cm margin. VMAT plans with 2–3 arcs were analyzed.ResultsA planning study was performed for five pts. including two pts. with primary tumor (PT) in head and neck, 1 pt. each with PT of elbow, forearm and upper leg respectively. Plans showed satisfactory PTV coverage: Dmean 100%±0%, D98% 92.4%±2.24%, homogeneity index (HI) 0.095±0.01, conformation number (CN) 0.84±0.01 and conformality index (CI) 0.95±0.01.ConclusionThe planning study confirms feasibility of highly conformal irradiation of IT pathways based on individualized target delineation. Currently, patients referred for non-metastatic MCC are encouraged to enroll in a prospective clinical study that evaluates the feasibility of radiation of IT pathways.



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Editorial Board

Publication date: March 2017
Source:Radiotherapy and Oncology, Volume 122, Issue 3





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Positron emission tomography and computed tomographic imaging (PET/CT) for dose planning purposes of thoracic radiation with curative intent in lung cancer patients: A systematic review and meta-analysis

Publication date: Available online 8 March 2017
Source:Radiotherapy and Oncology
Author(s): Andreas Hallqvist, Charlotte Alverbratt, Annika Strandell, Ola Samuelsson, Emil Björkander, Ann Liljegren, Per Albertsson
Background and purposePET/CT is a proposed management to improve the accuracy of high dose radiochemotherapy in lung cancer patients. This systematic review was performed to investigate the possible impact on clinical outcome and to quantify the effect on patient selection and target definition.Material and methodsSystematic literature searches were conducted, eligible full-text articles were assessed for quality and data were extracted.ResultsThirty-five cross-sectional studies and one observational study fulfilled the inclusion criteria. No randomized trials or data with regard to clinical endpoints were found. The summary estimates of a change in target definition were 36% in patients with a former staging PET, and 43% and 26% in patients without a staging PET, for non small- and small cell lung cancer respectively. The corresponding summary estimates of a change in treatment intent from curative to palliative treatment were 20% and 22% and 9% respectively.ConclusionPET/CT for dose planning improves target definition and patient selection. Approximately two in five patients had a significant change in target definition and one in five received palliative treatment instead. The proportions seem to be similar regardless of the availability of a previous staging-PET.



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Contents

Publication date: March 2017
Source:Radiotherapy and Oncology, Volume 122, Issue 3





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Important ESTRO dates

Publication date: March 2017
Source:Radiotherapy and Oncology, Volume 122, Issue 3





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Variation in head and neck cancer care in the Netherlands

Publication date: Available online 8 March 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): M. de Ridder, A.J.M. Balm, R.J. Baatenburg de Jong, C.H.J. Terhaard, R.P. Takes, M. Slingerland, E. Dik, R.J.E. Sedee, J.G.A.M. de Visscher, H. Bouman, S.M. Willems, M.W. Wouters, L.E. Smeele, B.A.C. van Dijk




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Vasculopathie livédoïde secondaire à une maladie cœliaque

Publication date: Available online 7 March 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J. Henry, F. Brault, C. Brouillard, M. Baudin, A. Gervaise, J. Pouaha, J.-F. Cuny, A. Valois
IntroductionLa vasculopathie livédoïde (VL) est une maladie caractérisée cliniquement par des ulcérations douloureuses, une atrophie blanche et un livédo, et sur le plan histopathologique par une vasculopathie occlusive du derme. Elle peut être associée à des états procoagulants, tels que l'hyperhomocystéinémie (HHC).ObservationNous rapportons l'observation d'une femme de 52 ans souffrant d'une VL, chez qui une image tomodensitométrique anormale nous a permis de diagnostiquer une maladie cœliaque. Cette entéropathie avait entraîné une carence en vitamine B12 et en folates érythrocytaires, puis une HHC. Une supplémentation vitaminique et un régime sans gluten ont permis la cicatrisation complète des lésions.DiscussionCette observation illustre l'importance de rechercher et corriger des troubles de la coagulation chez les patients atteints de vasculopathie livédoïde. Elle suggère de plus que, devant la découverte d'une hyperhomocystéinémie, une maladie cœliaque doit être recherchée même en l'absence de signes digestifs.BackgroundLivedoid vasculopathy (LV) is a painful ulcerative condition involving white atrophy and livedo; a histopathologic feature seen is occlusive dermal vasculopathy. This may be associated with coagulation disorders such as hyperhomocysteinaemia (HHC).Patients and methodsWe report the case of a 52-year-old woman presenting LV in which an abnormal scan image led us to diagnose coeliac disease. This enteropathy had caused vitamin B12 and folic acid deficiency, as well as HHC. Vitamin supplementation and a gluten-free diet resulted in complete healing of the lesions.DiscussionThis case underlines the importance of screening for and correction of coagulation disorders in patients with LV. It also suggests that in the event of HHC, coeliac disease should be sought, even in the absence of gastrointestinal symptoms.



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Psychological factors associated with uptake of the childhood influenza vaccine and perception of post-vaccination side-effects: A cross-sectional survey in England

Publication date: Available online 8 March 2017
Source:Vaccine
Author(s): Louise E. Smith, Rebecca K. Webster, John Weinman, Richard Amlôt, Jenny Yiend, G. James Rubin
ObjectivesTo identify predictors of: uptake of the childhood influenza vaccine in the 2015–2016 influenza season, parental perceptions of side-effects from the influenza vaccine and intention to vaccinate one's child for influenza in the 2016–2017 influenza season.DesignCross-sectional online survey.SettingData were collected in England shortly after the end of the 2015–2016 immunization campaign.Participants1001 parents or guardians of children aged between two and seven.Main outcome measuresSelf-reported uptake of the childhood influenza vaccine in the 2015–2016 influenza season, perception of side-effects from the influenza vaccine and intention to vaccinate one's child in the 2016–2017 influenza season.ResultsSelf-reported uptake of the childhood influenza vaccine was 52.8%. Factors strongly positively associated with uptake included the child having previously been vaccinated against influenza, perceiving the vaccine to be effective and perceiving the child to be susceptible to flu. Factors strongly negatively associated with uptake included perceiving the vaccine to be unsafe, to cause short-term side-effects or long-term health problems and believing that yearly vaccination may overload the immune system. Predictors of intended vaccine uptake in 2016–2017 were similar. Participants who perceived side-effects after the 2015–2016 vaccination reported being less likely to vaccinate their child next year.Side-effects were more likely to be reported in first-born children, by participants who knew another child who had side-effects, those who thought that the vaccine would interact with medication that the child was currently taking, and those who believed the vaccine causes short-term side-effects.ConclusionsPerceptions about the childhood influenza vaccine show strong associations with uptake, intended uptake and perception of side-effects. Attempts to improve uptake rates from their current low levels must address these perceptions.



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Cutaneous vaccination: Briefings of the third skin vaccination summit, September 2–4, 2015, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

Publication date: Available online 8 March 2017
Source:Vaccine
Author(s): Yotam Levin, Efrat Kochba, Sachin Mani




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Demethylase Kdm6a epigenetically promotes IL-6 and IFN-β production in macrophages

Publication date: Available online 8 March 2017
Source:Journal of Autoimmunity
Author(s): Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown. Here we found that Kdm6a, significantly downregulated via JNK pathway upon innate stimuli, promotes cytokine IL-6 and IFN-β transcription in primary macrophages during innate response. Kdm6a promoted IL-6 expression through demethylating H3K27me3 at promoter in a demethylase enzymatic activity-dependent manner. Interestingly, Kdm6a promoted IFN-β expression independent of its demethylase enzymatic activity, but through increasing transcription of IFN-β-specific enhancer-derived RNA (eRNA) S-IRE1. For the underlying mechanism, Kdm6a interacted with MLL4 and promoted MLL4 recruitment and H3K4me2 level in S-IRE1 region of Ifnb1 gene for full activation of enhancer. Our results reveal a previously unknown role of kdm6a in promoting innate IFN-β gene transcription at enhancer, in addition to demethylation at promoter. The function of Kdm6a in promoting innate inflammatory response also adds insights to better understanding of epigenetic modifiers in inflammatory and autoimmune disease.

Graphical abstract

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Identify and analysis crotonylation sites in histone by using support vector machines

Publication date: Available online 7 March 2017
Source:Artificial Intelligence in Medicine
Author(s): Wang-Ren Qiu, Bi-Qian Sun, Hua Tang, Jian Huang, Hao Lin
ObjectiveLysine crotonylation (Kcr) is a newly discovered histone posttranslational modification, which is specifically enriched at active gene promoters and potential enhancers in mammalian cell genomes. Although lysine crotonylation sites can be correctly identified with high-resolution mass spectrometry, the experimental methods are time-consuming and expensive. Therefore, it is necessary to develop computational methods to deal with this problem.MethodsWe proposed a new encoding scheme named position weight amino acid composition to extract sequence information of histone around crotonylation sites. We chose protein data from Uniprot database. A series of steps were used to construct a strict and objective benchmark dataset for training and testing the proposed method. All samples were characterized by a significant number of features derived from position weight amino acid composition. The support vector machine was used to perform classification.ResultsBased on a series of experiments, we found that the sensitivity (Sn), specificity (Sp), accuracy (Acc), and Matthew's correlation coefficient (MCC) were respectively 71.69%, 98.7%, 94.43%, and 0.778 in jackknife cross-validation. Comparison results demonstrated that our proposed model was better than random forest algorithm. We also performed the feature analysis on samples.ConclusionIdentification of the Kcr sites in histone is an indispensable step for decoding protein function. Therefore, the method can promote the deep understanding of the physiological roles of crotonylation and provide useful information for developing drugs to treat various diseases associated with crotonylation.



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SANTAVAC ™: A Novel Universal Antigen Composition for Developing Cancer Vaccines

Background: Development of a universal cancer vaccine for the prevention of all cancers has been under development for many years. Antiangiogenic cancer vaccines elicit immune responses with the potential of destroying tumor vasculature endothelial cells without affecting vasculature integrity in normal tissues. The methods used in the development of antigen compositions comprising these vaccines have been recently improved and described in this report in the context of SANTAVAC ™ development - the first cancer vaccine based on endothelial cell heterogeneity. <p></p> Methods: The present report summarizes data related to SANTAVAC™ development, including technical key points associated with optimal SANTAVAC™ production, a description of the composition required for preparing cancer vaccines with the highest predicted efficacy and safety, and a strategy for SANTAVAC™ large-scale implementation. Patents related to SANTAVAC™ and other universal cancer vaccines are also described. <p></p> Results: SANTAVAC ™ was shown to be the most promising antigen composition for anti-cancer vaccination, allowing for immune targeting of the tumor vasculature in experimental models with a high predicted efficacy (up to 60), where efficacy represents the fold decrease in the number of endothelial cells with a tumor-induced phenotype and directly related to predicted arrest of tumor growth. <p></p> Conclusion: The use of SANTAVAC ™ as a universal antigenic composition may spur vaccine development activities resulting in a set of therapeutic or prophylactic vaccines against different types of solid cancers. <p></p>

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