Biomechanical and morphological study of a new elastic mesh (Ciberlastic) to repair abdominal wall defects

The aim of this study was to conduct a preclinical evaluation of the behaviour of a new type of abdominal LW prosthesis (Ciberlastic), which was designed with a non-absorbable elastic polyurethane monofilament (Assuplus, Assut Europe, Italy) to allow greater adaptability to mechanical area requirements and higher bio-mimicking with the newly formed surrounding tissues. Our hypothesis was that an increase in the elasticity of the mesh filament could improve the benefits of LW prostheses. To verify our hypothesis, we compared the short- and long-term behaviour of Ciberlastic and Optilene® elastic commercial meshes by repairing the partially herniated abdomen in New Zealand White rabbits. The implanted meshes were mechanically and histologically assessed at 14 and 180 days post-implant. We mechanically characterized the partially herniated repaired muscle tissue and also determined mesh shrinkage at different post-implant times. This was followed by a histological study in which the tissue incorporation process was analysed over time. The new prosthesis designed by our group achieved good behaviour that was similar to that of Optilene®, one of the most popular LW prostheses on the market, with the added advantage of its elastic property. The mechanical properties are significantly lower than those of the polypropylene Optilene® mesh, and the new elastic mesh meets the basic mechanical requirements for positioning in the abdominal wall, which was also demonstrated by the absence of recurrences after implantation in the experimental model. We found that the growth of a connective tissue rich in collagen over the hernial defect and the proper deposit of the collagen fibres in the regenerated tissue substantially modified the original properties of the mesh, thereby increasing its biomechanical strength and making the whole tissue/mesh stiffer

International guidelines for groin hernia management

Worldwide, more than 20 million patients undergo groin hernia repair annually. The many different approaches, treatment indications and a significant array of techniques for groin hernia repair warrant guidelines to standardize care, minimize complications, and improve results. The main goal of these guidelines is to improve patient outcomes, specifically to decrease recurrence rates and reduce chronic pain, the most frequent problems following groin hernia repair. They have been endorsed by all five continental hernia societies, the International Endo Hernia Society and the European Association for Endoscopic Surgery. An expert group of international surgeons (the HerniaSurge Group) and one anesthesiologist pain expert was formed. The group consisted of members from all continents with specific experience in hernia-related research. Care was taken to include surgeons who perform different types of repair and had preferably performed research on groin hernia surgery. During the Group's first meeting, evidence-based medicine (EBM) training occurred and 166 key questions (KQ) were formulated. EBM rules were followed in complete literature searches (including a complete search by The Dutch Cochrane database) to January 1, 2015 and to July 1, 2015 for level 1 publications. The articles were scored by teams of two or three according to Oxford, SIGN and Grade methodologies. During five 2-day meetings, results were discussed with the working group members leading to 136 statements and 88 recommendations. Recommendations were graded as "strong" (recommendations) or "weak" (suggestions) and by consensus in some cases upgraded. In the Results and summary section below, the term "should" refers to a recommendation. The AGREE II instrument was used to validate the guidelines. An external review was performed by three international experts. They recommended the guidelines with high scores. The risk factors for inguinal hernia (IH) include: family history, previous contra-lateral hernia, male gender, age, abnormal collagen metabolism, prostatectomy, and low body mass index. Peri-operative risk factors for recurrence include poor surgical techniques, low surgical volumes, surgical inexperience and local anesthesia. These should be considered when treating IH patients. IH diagnosis can be confirmed by physical examination alone in the vast majority of patients with appropriate signs and symptoms. Rarely, ultrasound is necessary. Less commonly still, a dynamic MRI or CT scan or herniography may be needed. The EHS classification system is suggested to stratify IH patients for tailored treatment, research and audit. Symptomatic groin hernias should be treated surgically. Asymptomatic or minimally symptomatic male IH patients may be managed with "watchful waiting" since their risk of hernia-related emergencies is low. The majority of these individuals will eventually require surgery; therefore, surgical risks and the watchful waiting strategy should be discussed with patients. Surgical treatment should be tailored to the surgeon's expertise, patient- and hernia-related characteristics and local/national resources. Furthermore, patient health-related, life style and social factors should all influence the shared decision-making process leading up to hernia management. Mesh repair is recommended as first choice, either by an open procedure or a laparo-endoscopic repair technique. One standard repair technique for all groin hernias does not exist. It is recommended that surgeons/surgical services provide both anterior and posterior approach options. Lichtenstein and laparo-endoscopic repair are best evaluated. Many other techniques need further evaluation. Provided that resources and expertise are available, laparo-endoscopic techniques have faster recovery times, lower chronic pain risk and are cost effective. There is discussion concerning laparo-endoscopic management of potential bilateral hernias (occult hernia issue). After patient consent, during TAPP, the contra-lateral side should be inspected. This is not suggested during unilateral TEP repair. After appropriate discussions with patients concerning results tissue repair (first choice is the Shouldice technique) can be offered. Day surgery is recommended for the majority of groin hernia repair provided aftercare is organized. Surgeons should be aware of the intrinsic characteristics of the meshes they use. Use of so-called low-weight mesh may have slight short-term benefits like reduced postoperative pain and shorter convalescence, but are not associated with better longer-term outcomes like recurrence and chronic pain. Mesh selection on weight alone is not recommended. The incidence of erosion seems higher with plug versus flat mesh. It is suggested not to use plug repair techniques. The use of other implants to replace the standard flat mesh in the Lichtenstein technique is currently not recommended. In almost all cases, mesh fixation in TEP is unnecessary. In both TEP and TAPP it is recommended to fix mesh in M3 hernias (large medial) to reduce recurrence risk. Antibiotic prophylaxis in average-risk patients in low-risk environments is not recommended in open surgery. In laparo-endoscopic repair it is never recommended. Local anesthesia in open repair has many advantages, and its use is recommended provided the surgeon is experienced in this technique. General anesthesia is suggested over regional in patients aged 65 and older as it might be associated with fewer complications like myocardial infarction, pneumonia and thromboembolism. Perioperative field blocks and/or subfascial/subcutaneous infiltrations are recommended in all cases of open repair. Patients are recommended to resume normal activities without restrictions as soon as they feel comfortable. Provided expertise is available, it is suggested that women with groin hernias undergo laparo-endoscopic repair in order to decrease the risk of chronic pain and avoid missing a femoral hernia. Watchful waiting is suggested in pregnant women as groin swelling most often consists of self-limited round ligament varicosities. Timely mesh repair by a laparo-endoscopic approach is suggested for femoral hernias provided expertise is available. All complications of groin hernia management are discussed in an extensive chapter on the topic. Overall, the incidence of clinically significant chronic pain is in the 10-12% range, decreasing over time. Debilitating chronic pain affecting normal daily activities or work ranges from 0.5 to 6%. Chronic postoperative inguinal pain (CPIP) is defined as bothersome moderate pain impacting daily activities lasting at least 3 months postoperatively and decreasing over time. CPIP risk factors include: young age, female gender, high preoperative pain, early high postoperative pain, recurrent hernia and open repair. For CPIP the focus should be on nerve recognition in open surgery and, in selected cases, prophylactic pragmatic nerve resection (planned resection is not suggested). It is suggested that CPIP management be performed by multi-disciplinary teams. It is also suggested that CPIP be managed by a combination of pharmacological and interventional measures and, if this is unsuccessful, followed by, in selected cases (triple) neurectomy and (in selected cases) mesh removal. For recurrent hernia after anterior repair, posterior repair is recommended. If recurrence occurs after a posterior repair, an anterior repair is recommended. After a failed anterior and posterior approach, management by a specialist hernia surgeon is recommended. Risk factors for hernia incarceration/strangulation include: female gender, femoral hernia and a history of hospitalization related to groin hernia. It is suggested that treatment of emergencies be tailored according to patient- and hernia-related factors, local expertise and resources. Learning curves vary between different techniques. Probably about 100 supervised laparo-endoscopic repairs are needed to achieve the same results as open mesh surgery like Lichtenstein. It is suggested that case load per surgeon is more important than center volume. It is recommended that minimum requirements be developed to certify individuals as expert hernia surgeon. The same is true for the designation "Hernia Center". From a cost-effectiveness perspective, day-case laparoscopic IH repair with minimal use of disposables is recommended. The development and implementation of national groin hernia registries in every country (or region, in the case of small country populations) is suggested. They should include patient follow-up data and account for local healthcare structures. A dissemination and implementation plan of the guidelines will be developed by global (HerniaSurge), regional (international societies) and local (national chapters) initiatives through internet websites, social media and smartphone apps. An overarching plan to improve access to safe IH surgery in low-resource settings (LRSs) is needed. It is suggested that this plan contains simple guidelines and a sustainability strategy, independent of international aid. It is suggested that in LRSs the focus be on performing high-volume Lichtenstein repair under local anesthesia using low-cost mesh. Three chapters discuss future research, guidelines for general practitioners and guidelines for patients. The HerniaSurge Group has developed these extensive and inclusive guidelines for the management of adult groin hernia patients. It is hoped that they will lead to better outcomes for groin hernia patients wherever they live. More knowledge, better training, national audit and specialization in groin hernia management will standardize care for these patients, lead to more effective and efficient healthcare and provide direction for future research

HALT (Hernia Active Living Trial): protocol for a feasibility study of a randomised controlled trial of a physical activity intervention to improve quality of life in people with bowel stoma with a bulge/parastomal hernia

Background Parastomal hernia (PSH) can be repaired surgically, but results to date have been disappointing, with reported recurrence rates of 30 to 76%. Other types of intervention are therefore needed to improve the quality of life of people with PSH. One potential intervention is physical activity. We hypothesise that the intervention will increase core activation and control across the abdominal wall at a site of potential weakness and thus reduce the risk of PSH progression. Increases in physical activity will improve body image and quality of life (QoL). Methods Subjects and sample There were approximately 20 adults with a bowel stoma and PSH. People with previous PSH repair will be excluded as well as people who already do core training. Study design This is a feasibility study of a randomised controlled trial with 2 months follow-up, in 2 sites using mixed methods. Stage 1 involves intervention development and in stage 2, intervention and trial parameters will be assessed. Intervention A theoretically informed physical activity intervention was done, targeting people with PSH. Main outcome of feasibility study The main outcome is the decision by an independent Study Steering Committee whether to proceed to a full randomised controlled trial of the intervention. Other outcomes We will evaluate 4 intervention parameters—fidelity, adherence, acceptability and safety and 3 trial parameters (eligible patients’ consent rate, acceptability of study design and data availability rates for following endpoints): I. Diagnosis and classification of PSH II. Muscle activation III. Body composition (BMI, waist circumference) IV. Patient reported outcomes: QoL, body image and physical functioning V. Physical activity; VI. Psychological determinants of physical activity Other data Included are other data such as interviews with all participants about the intervention and trial procedures. Data analysis and statistical power As this is a feasibility study, the quantitative data will be analysed using descriptive statistics. Audio-recorded qualitative data from interviews will be transcribed verbatim and analysed thematically. Discussion The feasibility and acceptability of key intervention and trial parameters will be used to decide whether to proceed to a full trial of the intervention, which aims to improve body image, quality of life and PSH progression. Trial registration ISRCTN1520759

Вплив особистості на бренд-неймінг сімейного бізнесу

Бренд сімейного бізнесу персоніфікує його на ринку пов’язуючи з особистістю її власника. У статті проаналізовано специфіку процесу правонаступництва поколінь у сімейних компаніях Чеської Республіки, а також систематизовано основні проблеми та шляхи їх вирішення. Метою даної статті є виявлення та обґрунтування можливих ризиків впливу особистості на бренд-неймінг сімейного бізнесу. Авторами узагальнено можливі ризики функціонування сімейного бізнесу за умови участі представників сім’ї в менеджменті, а також спадковим правонаступництвом сімейного бізнесу. Детерміновану вибірку даних сформовано на основі результатів опитування 245 власників сімейних підприємств Чеської Республіки. Для формування вибірки дослідження проведено круглі столи та дискусії у період з 2017 року по 2019 рік. Методологію дослідження засновано на кореляційному та регресійному аналізах. За результатами дослідження авторами зроблено висновку, що власники сімейного бізнесу вважають потенційним ризиком асоціацію компанії з їх особистістю. Будь-яке негативне ставлення до сімейної компанії може негативно віддзеркалитись на сім’ю, тоді як негативне ставлення до сім'ї погіршує репутацію компанії. Це у свою чергу провокує відтік споживачів та працівників. Авторами зазначено, що це також може негативно вплинути на процес правонаступництва за умови спадкоємстві від одного покоління до іншого. Емпіричні результати аналізу згенерованої вибірки даних засвідчили статистично значущий взаємозв’язок між рівнем сприйняттям ризику та спадковим правонаступництвом сімейного бізнесу. Враховуючи отримані результати, авторами визначено, що високий ступінь сприйняття ризику характерний для сімейних компаній зі спадковим правонаступництвом. Перспективами подальших досліджень є аналіз статистичної значущості за умови виключення змінної асоціації назви сімейної компанії із особистістю через високий ступінь їх колінеарності.A company's name often personifies the company. In the case of family companies, the name is mainly connected with that of the owning family. This paper aims to identify and substantiate the context of the perception of any possible risks from the association of a family name with that of a family company during the generational exchange with the participation of several generations in the family company's management. The hypotheses have been verified based on the evaluation of data acquired from a sample of 245 respondents from the Czech Republic. The research period is 2017-2019. The qualitative research is based on round discussion tables with family business owners. The data has been processed using correlation and regression analysis. The authors have shown that owners consider the association of the family name with that of a family company to be a potential risk. Any negative regard for the family company and the family could lead to losing the family's good name and the company and losing customers and employees. Moreover, it could damage the process of intergenerational transition. The connection between the intensity of the risk perception and the generational exchange process with the participation of several members in the management of a family company has been statistically demonstrated. The degree of perception of the risk is high in family companies where the generational exchange is still ongoing. The exclusion of the variable of the connection of a family company name with the owning family due to collinearity suggests a possibility for a different type of research that would demonstrate the statistical significance. The unique article nature lies in the fact that it involves research into the current, real process of generational exchange taking place in Czech family companies with mainly two generations and up to three generations in the family company management

Structural analysis of human 2 O ribose methyltransferases involved in mRNA cap structure formation.

The 5′ cap of human messenger RNA contains 2′-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding