[Otorhinolaryngology in the field of demography, growing outpatient care and regionalization]. / Die HNO-Heilkunde im Spannungsfeld von Ambulantisierung und Regionalisierung.

BACKGROUND: Otorhinolaryngology (ENT) departments are strongly affected by current changes in the reimbursement schemes for inpatients. The study was designed to investigate these effects on the ENT Department in Rostock and selected comparison clinics, as well as to outline solutions. METHODS: We analyzed diagnosis-related group (DRG) reports of the ENT Clinic at Rostock University Medical Center from 2013 to 2015, according to the size of the outpatient potential. Comparisons were made with other surgical departments such as maxillofacial surgery and ophthalmology in terms of average length of stay and the resulting deductibles. We also compared billing as day surgery and complete outpatient surgery for the main small surgical procedures such as tonsillectomy and septum surgery. Finally, we compared the discounts with 22 ENT departments in other maximum care hospitals. RESULTS: The average case mix index of an ENT department in Germany is 0.75, case load average of 2,500 patients and common length of stay 4.1 days. In a typical academic ENT department as in Rostock, health plans usually discount around 500 T€ (thousand euro), which is considerably higher than comparable departments, e.g., oral and maxillofacial surgery or ophthalmology departments. However, discounts on a DRG for inpatient surgery is still approximately 1,000 € more revenue than surgery in an outpatient setting. The benchmark analysis shows that health plans in rural areas are more likely to accept inpatient surgery with discounts for small procedures than strict billing according to outpatient reimbursement schemes. CONCLUSION: These effects can result in an insufficient cost effectiveness of ENT departments in Germany. As a consequence, substantial restructuring of the in- and outpatient treatment seems necessary, also for academic ENT departments, e.g., in the form of day surgery or ambulatory surgical centers, outpatient clinics with special contracts and specialized inpatient surgery. However, this results in greater demands on the training of young physicians and management of patient flows within the department.

[OR minute myth : Guidelines for calculation of DRG revenues per OR minute]. / Mythos OP-Minute : Leitfaden zur Kalkulation von DRG-Erlösen pro Op-Minute.

The economic situation in German Hospitals is tense and needs the implementation of differentiated controlling instruments. Accordingly, parameters of revenue development of different organizational units within a hospital are needed. This is particularly necessary in the revenue and cost-intensive operating theater field. So far there are only barely established productivity data for the control of operating room (OR) revenues during the year available. This article describes a valid method for the calculation of case-related revenues per OR minute conform to the diagnosis-related groups (DRG).For this purpose the relevant datasets from the OR information system and the § 21 productivity report (DRG grouping) of the University Medical Center Göttingen were combined. The revenues defined in the DRG browser of the Institute for Hospital Reimbursement (InEK) were assigned to the corresponding process times--incision-suture time (SNZ), operative preparation time and anesthesiology time--according to the InEK system. All full time stationary DRG cases treated within the OR were included and differentiated according to the surgical department responsible. The cost centers "OR section" and "anesthesia" were isolated to calculate the revenues of the operating theater. SNZ clusters and cost type groups were formed to demonstrate their impact on the revenues per OR minute. A surgical personal simultaneity factor (GZF) was calculated by division of the revenues for surgeons and anesthesiologists. This factor resembles the maximum DRG financed personnel deployment for surgeons in German hospitals.The revenue per OR minute including all cost types and DRG was 16.63 €/min. The revenues ranged from 10.45 to 24.34 €/min depending on the surgical field. The revenues were stable when SNZ clusters were analyzed. The differentiation of cost type groups revealed a revenue reduction especially after exclusion of revenues for implants and infrastructure. The calculated GZF over all surgical departments was 2.2 (range 1.9-3.6). A calculation of this factor at the DRG level can give economically relevant information about the case-related personnel deployment.This analysis shows for the first time the DRG-conform calculation of revenues per OR minute. There is a strong dependency on the considered cost type and the performing surgical field. Repetitive analyses are necessary due to the lack of reference values and are a suitable tool to monitor the revenue development after measures for process optimization. Comparative analyses within different surgical fields on this data base should be avoided. The demonstrated method can be used as a guideline for other hospitals to calculate the DRG revenues within the OR. This enables pursuing cost-effectiveness analysis by comparing these revenues with cost data from the cost unit accounting at a DRG or case level.

[Errors in medicine. Causes, impact and improvement measures to improve patient safety]. / Fehler in der Medizin. Ursachen, Auswirkungen und Maßnahmen zur Verbesserung der Patientensicherheit.

The guarantee of quality of care and patient safety is of major importance in hospitals even though increased economic pressure and work intensification are ubiquitously present. Nevertheless, adverse events still occur in 3-4 % of hospital stays and of these 25-50 % are estimated to be avoidable. The identification of possible causes of error and the development of measures for the prevention of medical errors are essential for patient safety. The implementation and continuous development of a constructive culture of error tolerance are fundamental.The origins of errors can be differentiated into systemic latent and individual active causes and components of both categories are typically involved when an error occurs. Systemic causes are, for example out of date structural environments, lack of clinical standards and low personnel density. These causes arise far away from the patient, e.g. management decisions and can remain unrecognized for a long time. Individual causes involve, e.g. confirmation bias, error of fixation and prospective memory failure. These causes have a direct impact on patient care and can result in immediate injury to patients. Stress, unclear information, complex systems and a lack of professional experience can promote individual causes. Awareness of possible causes of error is a fundamental precondition to establishing appropriate countermeasures.Error prevention should include actions directly affecting the causes of error and includes checklists and standard operating procedures (SOP) to avoid fixation and prospective memory failure and team resource management to improve communication and the generation of collective mental models. Critical incident reporting systems (CIRS) provide the opportunity to learn from previous incidents without resulting in injury to patients. Information technology (IT) support systems, such as the computerized physician order entry system, assist in the prevention of medication errors by providing information on dosage, pharmacological interactions, side effects and contraindications of medications.The major challenges for quality and risk management, for the heads of departments and the executive board is the implementation and support of the described actions and a sustained guidance of the staff involved in the modification management process. The global trigger tool is suitable for improving transparency and objectifying the frequency of medical errors.

[Implementation of a rational standard of hygiene for preparation of operating rooms]. / Implementierung eines rationalen Hygienestandards zur Aufbereitung von Operationssälen.

BACKGROUND: The assurance of high standards of care is a major requirement in German hospitals while cost reduction and efficient use of resources are mandatory. These requirements are particularly evident in the high-risk and cost-intensive operating theatre field with multiple process steps. The cleaning of operating rooms (OR) between surgical procedures is of major relevance for patient safety and requires time and human resources. The hygiene procedure plan for OR cleaning between operations at the university hospital in Göttingen was revised and optimized according to the plan-do-check-act principle due to not clearly defined specifications of responsibilities, use of resources, prolonged process times and increased staff engagement. METHODS: The current status was evaluated in 2012 as part of the first step "plan". The subsequent step "do" included an expert symposium with external consultants, interdisciplinary consensus conferences with an actualization of the former hygiene procedure plan and the implementation process. All staff members involved were integrated into this management change process. The penetration rate of the training and information measures as well as the acceptance and compliance with the new hygiene procedure plan were reviewed within step "check". The rates of positive swabs and air sampling as well as of postoperative wound infections were analyzed for quality control and no evidence for a reduced effectiveness of the new hygiene plan was found. After the successful implementation of these measures the next improvement cycle ("act") was performed in 2014 which led to a simplification of the hygiene plan by reduction of the number of defined cleaning and disinfection programs for preparation of the OR. RESULTS: The reorganization measures described led to a comprehensive commitment of the hygiene procedure plan by distinct specifications for responsibilities, for the course of action and for the use of resources. Furthermore, a simplification of the plan, a rational staff assignment and reduced process times were accomplished. Finally, potential conflicts due to an insufficient evidence-based knowledge of personnel was reduced. CONCLUSION: This present project description can be used by other hospitals as a guideline for similar changes in management processes.

[Quality assurance at the interface between anesthesia and transfusion medicine]. / Qualitätssicherung an der Schnittstelle zwischen Anästhesie und Transfusionsmedizin.

BACKGROUND: The current situation in hospitals is characterized by financial limitations and simultaneously by increasing demands on quality and safety. The operative interface between anesthesia and transfusion medicine affects both factors. AIM: A detailed analysis was performed to evaluate the process quality at this operative interface at the University Hospital of Göttingen. The aim of the project was to revise und develop the structures and responsibilities at this interface, to dispose of weak points and to realize the optimization potential in the supply of blood products. MATERIAL AND METHODS: A databank-based electronic data processing solution was established with the clear definition of responsibilities for the various workflow procedures and the written documentation of these definitions in standard operating protocols. In order to guarantee the necessary transparency a routine reporting system to the department of surgery was established. In addition, a continuous further development of the blood supply standard based on electronic report data was implemented. RESULTS: By implementing the above named measures the rate of supplied to transfused blood products could be increased from 43.1 % to 55.7 %. The compliance with the blood supply standard improved continually over the first 18 months from 60.3 % to 92.3 %. The rate of supplied blood product deliveries without subsequent operation could be reduced from 9.0 % to 4.6 %. As a result of this optimization the supply costs in the internal cost allocation were reduced from 9,406  to 3,544 . CONCLUSION: The measures described are appropriate to cost-effectively improve quality and patient safety. The optimization measures presented in this article can be implemented in other hospitals to increase quality and safety after individual adjustment to the local circumstances.

[Second victim : Critical incident stress management in clinical medicine]. / "Second victim" : "Critical incident stress management" in der klinischen Medizin.

BACKGROUND: Critical incidents in clinical medicine can have far-reaching consequences on patient health. In cases of severe medical errors they can seriously harm the patient or even lead to death. The involvement in such an event can result in a stress reaction, a so-called acute posttraumatic stress disorder in the healthcare provider, the so-called second victim of an adverse event. Psychological distress may not only have a long lasting impact on quality of life of the physician or caregiver involved but it may also affect the ability to provide safe patient care in the aftermath of adverse events. METHODS: A literature review was performed to obtain information on care giver responses to medical errors and to determine possible supportive strategies to mitigate negative consequences of an adverse event on the second victim. An internet search and a search in Medline/Pubmed for scientific studies were conducted using the key words "second victim, "medical error", "critical incident stress management" (CISM) and "critical incident stress reporting system" (CIRS). Sources from academic medical societies and public institutions which offer crisis management programs where analyzed. The data were sorted by main categories and relevance for hospitals. Analysis was carried out using descriptive measures. RESULTS: In disaster medicine and aviation navigation services the implementation of a CISM program is an efficient intervention to help staff to recover after a traumatic event and to return to normal functioning and behavior. Several other concepts for a clinical crisis management plan were identified. CONCLUSIONS: The integration of CISM and CISM-related programs in a clinical setting may provide efficient support in an acute crisis and may help the caregiver to deal effectively with future error events and employee safety.

[Generation 55+: leadership and motivation of generations in hospitals]. / Generation 55 + : Führung und Motivation von Generationen im Krankenhaus.

BACKGROUND: Demographic changes in Germany are leading towards a decrease of the population from the current 82 million to 74 million in the year 2050. As a consequence the shortage of qualified staff will be aggravated and intensifying recruiting efforts will increase competition among employers. An alternative is to utilize the potential of jobholders older than 55 years, the so-called generation 55 +. However, little is known about the hospital workforce generation 55 +. METHODS: An internet search was conducted using google.de, yahoo.de and altavista.de for "generation 55 + and medicine" and "demographics, personnel and hospital" In Medline/pubmed a search was conducted for the key words "aging workforce" (949 sources) and in combination with AND "doctors" (134 sources), "demographic changes", "staff" (794 sources) as well as for "generation 55 + AND doctors" (312 sources). Finally, sources from reputable public institutions and academic medical societies were analyzed. The data were sorted by main categories and relevance for hospitals. Statistical analysis was done mainly using descriptive measures. RESULTS: From initially more than 530,000 sources, a total of 289 studies and reports on the topic were plotted. There was no evidence for a negative correlation between age and work ability or fitness. Jobholders senior to 55 years can be divided into the "economic miracle generation" and into the so-called baby-boomers. Both groups have differences in values, communication needs and leadership requirements. They jointly prefer direct communication and seek appreciation for their experience on the job. CONCLUSIONS: Generation 55 + is not asking for an upscaled position in hospitals. They expect respect and appreciation for their sound experience of work and life. Generation 55 + wants to be integrated and sought after. Keeping these employees fit, motivated and qualified is a sound approach to fight the foreseeable shortage of qualified staff in hospitals.

[Generation Y in ENT: leading a young generation of doctors]. / Generation Y in der HNO: Führung einer neuen Generation von Ärzten.

BACKGROUND: The shortage of qualified doctors and nurses has led to a competition between hospitals. Analyzing the circumstances of the competition, nurses and doctors of so-called generation Y are important. These employees are mainly female and have different requirements compared to previous generations. Therefore, knowledge of these requirements will become a critical success factor for hospitals in the future. METHOD: We interviewed medical students in Kiel and Hannover from 2005 to 2011 about the clinical department chosen, the criteria for choosing a specific clinic, and the importance of MD and PhD programs. In addition, we conducted an internet and Medline search for scientific studies on labor shortage, generation Y, and demographics. The data were sorted by main categories and relevance for hospitals. Statistical analyses were performed using descriptive measures. RESULTS: We received 1,097 answers which represents approx. 75% of all students. Sixty-seven percent of the students were female, 33% male. Preferences for departments revealed internal medicine, pediatrics, and anesthesiology as the top three. ENT followed at rank 10. The main criteria for choosing a clinic were working climate, structure and broadness of education, family friendliness, and respect. MD programs were rated 2.6, while PhD programs were rated 3.6. Staff members of Generation Y "live while working" and disagree with hierarchies. Internet and computers are part of their daily routine. CONCLUSION: Employees of Generation Y challenge leadership in hospitals by increasing demands. However, Generation Y can increase professionalization and competitiveness for hospitals significantly.

[The shortage of qualified staff in Germany: a survey on head physicians' expectations of young doctors]. / Fachkräftemangel in Deutschland: Umfrage zu Erwartungen von Chefärzten an junge Mitarbeiter.

BACKGROUND: The shortage of medical specialists in Germany has led to increased competition between hospitals, particularly in the recruitment of young skilled doctors. The quality of training appears to be the critical factor in a clinic's recruiting process. At the same time, the suitability of candidates is decreasing. There is currently no data on the suitability of candidates for otorhinolaryngology, nor are there any forecasts about the labor shortage in this speciality. METHODS: We compiled a questionnaire according to accepted guidelines, which was then sent to 160 ENT departments by email. We asked about the size and location of the department and the number of applicants that were suitable or unsuitable. Finally, we asked about the current availability of staff as well as the requirements set by the head physician. RESULTS: The response rate was 34% (54 questionnaires). Departments received an average of 20 applications per year, of which 36% were unsuitable. Departments received more applications in the new German states than in the old; however, no difference in the quality of candidates was seen. University hospitals receive almost three times more applications than other hospitals. The size of the department correlates with the number of applications and quality of the candidates. Almost 60% of chief physicians expected the lack of qualified staff to worsen in the future. However, 40% of chief physicians of large departments (> 50 beds) expected the situation to improve or remain unchanged. Chief physicians' main expectations of candidates included commitment, independent learning and team spirit. CONCLUSIONS: A broad and structured residency program for new employees is the most important factor in the recruitment of new physicians. Large departments and university hospitals have advantages here. The expectations of head physicians differ from those of young staff in terms of commitment and autonomous learning.

[Generation Y : recruitment, retention and development]. / Generation Y : Rekrutierung, Entwicklung und Bindung.

BACKGROUND: There is a significant shortage of highly qualified personnel in medicine, especially skilled doctors and nurses. This shortage of qualified labor has led to competition between hospitals. Analyzing the circumstances of the competition, nurses and doctors of the so-called generation Y are of importance. Recruitment and retention of these staff members will become a critical success factor for hospitals in the future. METHOD: An internet search was conducted using the key words "generation Y and medicine, demography, personnel and hospitals". A search in Medline/pubmed for scientific studies on the topics of labor shortage was performed using the key words "personnel, shortage doctors, generation X, baby boomer, personnel and demographic changes, staff". Finally, sources from public institutions and academic medical societies were analyzed. The data were sorted by main categories and relevance for hospitals. Statistical analysis was done using descriptive measures. RESULTS: The analysis confirmed the heterogeneous and complex flood of information on the topic demography and generation. A comparison of the generations showed that they can be separated into baby boomers (born 1946-1964 live to work), generation X (born 1965-1980 work to live) and generation Y (born 1981 and after, live while working). Members of generation Y "live while working" are oriented to competence and less with hierarchies. They exchange information using modern communication methods and within networks. Internet and computers are part of their daily routine. CONCLUSION: Employees of generation Y challenge leadership in hospitals by increasing the demands. However, generation Y can significantly increase professionalization and competitiveness for hospitals.

[From personnel administration to human resource management : demographic risk management in hospitals]. / Von der Personalverwaltung zur Personalentwicklung : "Demographic risk management" in Krankenhäusern.

BACKGROUND: The healthcare market is facing a serious shortage of qualified personnel in 2020. Aging of staff members is one important driver of this human resource deficit but current planning periods of 1-2 years cannot compensate the demographic effects on staff portfolio early enough. Therefore, prospective human resource planning is important to avoid loss of competence. METHODS: The long range development (10 years) of human resources in the hospitals of the City of Cologne was analyzed. The basis for the analysis was a simulation model that included fluctuation of staff, retirement, maternity leave, status of employee illness, partial retirement and fresh engagements per department and profession. The model was matched with the staff requirements for each department. The results showed a capacity analysis which was used to convey strategic measures for staff recruitment and retention. RESULTS: The greatest risk for shortage of qualified staff was found in the fluctuation of doctors and in the aging work force. Without strategic human resource management the hospitals would face a 50% reduction of the work force within 10 years and after 2 years there would be a 25% deficit of anesthesiologists with impact on the function of operation rooms (OR) and intensive care units. Qualification and continuous training of staff members as well as process optimization are the most important spheres of activity for human resource management in order to recruit and retain qualified staff members. CONCLUSION: Prospective human resource planning for the OR and intensive care units can help to detect shortage of staff and loss of competence early enough to apply effective personnel development measures. A growing number of companies have started to plan ahead of the current demand of human resources. Hospitals should follow this example because the competition for qualified staff members is increasing rapidly.

[From guilt and shame to professional handling of mistakes--risk management in surgical medicine]. / Von Schuld und Scham zu einem professionellen Umgang mit Fehlern--Risikomanagement in der operativen Medizin.

Medical advances in diagnosis and therapy, especially in medical technology, lead to differenciated and more complex strategies in therapy with higher risks. Patients show higher expectations concerning the results of a therapy and claim more often that a mistake in treatment has been made. This makes patients turn to arbitration boards more often. They may also want to bring civil action against physicians and hospitals, claiming for compensation and damages. Personal liability insurances have to pay more for damages. Medical insurances have more recourse demands due to mistake in treatment. Hospital and especially operative medicine do have high chances of risks and mistakes. The implementation of a modern risk management system in the hospitals is becoming more and more important, for patients as well as for the surgical departments. A structured reporting system of critical incidents can produce indicators of potential sources of mistakes, which appears to be a successful approach to reduce or avoid typical risks and mistakes in medical treatment. Risk management in medical treatment must be more than just a trendy word, because its roots are in the medical principles of "primum nihil nocere". It is a challenge to today's and tomorrow's medicine. This article is a general overview of current strategies for avoiding mistakes: It is meant to be the basis of a new culture of mistake avoidance as a part of a future quality competition.

[Improvement of team competence in the operating room : Training programs from aviation]. / Verbesserung der Teamkompetenz im OP : Trainingsprogramme aus der Luftfahrt.

Growing attention has been drawn to patient safety during recent months due to media reports of clinical errors. To date only clinical incident reporting systems have been implemented in acute care hospitals as instruments of risk management. However, these systems only have a limited impact on human factors which account for the majority of all errors in medicine. Crew resource management (CRM) starts here. For the commissioning of a new hospital in Minden, training programs were installed in order to maintain patient safety in a new complex environment. The training was planned in three parts: All relevant processes were defined as standard operating procedures (SOP), visualized and then simulated in the new building. In addition, staff members (trainers) in leading positions were trained in CRM in order to train the complete staff. The training programs were analyzed by questionnaires. Selection of topics, relevance for practice and mode of presentation were rated as very good by 73% of the participants. The staff members ranked the topics communication in crisis situations, individual errors and compensating measures as most important followed by case studies and teamwork. Employees improved in compliance to the SOP, team competence and communication. In high technology environments with escalating workloads and interdisciplinary organization, staff members are confronted with increasing demands in knowledge and skills. To reduce errors under such working conditions relevant processes should be standardized and trained for the emergency situation. Human performance can be supported by well-trained interpersonal skills which are evolved in CRM training. In combination these training programs make a significant contribution to maintaining patient safety.

Integrin-cytoskeletal interactions in migrating fibroblasts are dynamic, asymmetric, and regulated.

We have used laser optical trapping and nanometer-level motion analysis to investigate the cytoskeletal associations and surface dynamics of beta 1 integrin, a cell-substrate adhesion molecule, on the dorsal surfaces of migrating fibroblast cells. A single-beam optical gradient trap (laser tweezers) was used to restrain polystyrene beads conjugated with anti-beta 1 integrin mAbs and place them at desired locations on the cell exterior. This technique was used to demonstrate a spatial difference in integrin-cytoskeleton interactions in migrating cells. We found a distinct increase in the stable attachment of beads, and subsequent rearward flow, on the lamellipodia of locomoting cells compared with the retracting portions. Complementary to the enhanced linkage of integrin at the cell lamellipodium, the membrane was more deformable at the rear versus the front of moving cells while nonmotile cells did not exhibit this asymmetry in membrane architecture. Video microscopy and nanometer-precision tracking routines were used to study the surface dynamics of integrin on the lamellipodia of migrating cells by monitoring the displacements of colloidal gold particles coated with anti-beta 1 integrin mAbs. Small gold aggregates were rapidly transported preferentially to the leading edge of the lamellipod where they resumed diffusion restricted along the edge. This fast transport was characterized by brief periods of directed movement ("jumps") having an instantaneous velocity of 37 +/- 15 microns/min (SD), separated by periods of diffusion. In contrast, larger aggregates of gold particles and the large latex beads underwent slow, steady rearward movement (0.85 +/- 0.44 micron/min) (SD) at a rate similar to that reported for other capping events and for migration of these cells. Cell lines containing mutated beta 1 integrins were used to show that the cytoplasmic domain is essential for an asymmetry in attachment of integrin to the underlying cytoskeletal network and is also necessary for rapid, intermittent transport. However, enhanced membrane deformability at the cell rear does not require integrin-cytoskeletal interactions. We also demonstrated that posttranslational modifications of integrin could potentially play a role in these phenomena. These results suggest a scheme for the role of dynamic integrin-mediated adhesive interactions in cell migration. Integrins are transported preferentially to the cell front where they form nascent adhesions. These adhesive structures grow in size and associate with the cytoskeleton that exerts a rearward force on them. Dorsal aggregates more rearward while those on the ventral side remain fixed to the substrate allowing the cell body to move forward. Detachment of the cell rear occurs by at least two modes: (a) weakened integrin-cytoskeleton interactions, potentially mediated by local modifications of linkage proteins, which lead to weakened cell-substratum interactions and (b) ripping of integrins and the highly deformable membrane from the cell body.

Development of an apoptosis-assisted decellularization method for maximal preservation of nerve tissue structure.

Preservation of tissue structure is often a primary goal when optimizing tissue and organ decellularization methods. Many current protocols nonetheless rely on detergents that aid extraction of cellular components but also damage tissue architecture. It may be more beneficial to leverage an innate cellular process such as apoptosis and promote cell removal without the use of damaging reagents. During apoptosis, a cell detaches from the extracellular matrix, degrades its internal components, and fragments its contents for easier clearance. We have developed a method that leverages this process to achieve tissue decellularization using only mild wash buffers. We have demonstrated that treating peripheral nerve tissue with camptothecin induced both an early marker of apoptosis, cleaved caspase-3 expression, as well as a late stage marker, TUNEL+ DNA fragmentation. Clearance of the cellular components was then achieved in an apoptosis-dependent manner using a gentle wash in hypertonic phosphate buffered saline followed by DNase treatment. This wash paradigm did not significantly affect collagen or glycosaminoglycan content, but it was sufficient to remove any trace of the cytotoxic compound based on conditioned media experiments. The resulting acellular tissue graft was immunogenically tolerated in vivo and exhibited an intact basal lamina microarchitecture mimicking that of native, unprocessed nerve. Hence, ex vivo induction of apoptosis is a promising method to decellularize tissue without the use of harsh reagents while better preserving the benefits of native tissue such as tissue-specific composition and microarchitecture. STATEMENT OF SIGNIFICANCE: Tissue decellularization has expanded the ability to generate non-immunogenic organ replacements for a broad range of health applications. Current technologies typically rely on the use of harsh agents for clearing cellular debris, altering the tissue structure and potentially diminishing the pro-regenerative effects. We have developed a method for effectively, yet gently, removing cellular components from peripheral nerve tissue while preserving the native tissue architecture. The novelty of this process is in the induction of programmed cell death - or apoptosis - via a general cytotoxin, thereby enabling antigen clearance using only hypertonic wash buffers. The resulting acellular nerve scaffolds are nearly identical to unprocessed tissue on a microscopic level and elicit low immune responses comparable to an isograft negative control in a model of subcutaneous implantation.

Optimizing neurotrophic factor combinations for neurite outgrowth.

Most neurotrophic factors are members of one of three families: the neurotrophins, the glial cell-line derived neurotrophic factor family ligands (GFLs) and the neuropoietic cytokines. Each family activates distinct but overlapping cellular pathways. Several studies have shown additive or synergistic interactions between neurotrophic factors from different families, though generally only a single combination has been studied. Because of possible interactions between the neurotrophic factors, the optimum concentration of a factor in a mixture may differ from the optimum when applied individually. Additionally, the effect of combinations of neurotrophic factors from each of the three families on neurite extension is unclear. This study examines the effects of several combinations of the neurotrophin nerve growth factor (NGF), the GFL glial cell-line derived neurotrophic factor (GDNF) and the neuropoietic cytokine ciliary neurotrophic factor (CNTF) on neurite outgrowth from young rat dorsal root ganglion (DRG) explants. The combination of 50 ng ml(-1) NGF and 10 ng ml(-1) of each GDNF and CNTF induced the highest level of neurite outgrowth at a 752 +/- 53% increase over untreated DRGs and increased the longest neurite length to 2031 +/- 97 microm compared to 916 +/- 64 microm for untreated DRGs. The optimum concentrations of the three factors applied in combination corresponded to the optimum concentration of each factor when applied individually. These results indicate that the efficacy of future therapies for nerve repair would be enhanced by the controlled release of a combination of neurotrophins, GFLs and neuropoietic cytokines at higher concentrations than used in previous conduit designs.

Functionalizing micro-3D-printed protein hydrogels for cell adhesion and patterning.

The extracellular matrix has been shown to profoundly influence both cell morphology and numerous cellular processes - including adhesion, differentiation, and alignment - through a range of chemical, mechanical, and topographical features. In these studies, we investigate a versatile platform for functionalizing micro-3D-printed (µ-3DP) protein hydrogels via multiphoton excitation of benzophenone-biotin, a photoactivatable ligand capable of reacting with the hydrogel matrix, which is subsequently linked to a biotinylated cell-adhesive peptide through a NeutrAvidin® bridge. This functionalization strategy is potentially applicable to a broad range of hydrogel platforms, enabling biomolecules to be precisely patterned at specified locations within 3D materials. As proof-of-concept of this strategy's utility, we demonstrate that chemical modifications can be made to µ-3DP protein hydrogels that enable Schwann cells to be patterned without altering the mechanical or topographical properties of the hydrogel to an extent that influences SC cell adhesion. The ability to independently control potential cellular cues within in vitro cellular microenvironments is essential to investigating decoupled effects of biomaterial properties on cell-matrix interactions. In addition, we demonstrate feasibility for generating arbitrary immobilized chemical gradient profiles, a result that opens important opportunities for understanding and controlling haptotactic behaviors, such as directed migration, that are key to various tissue regeneration applications.

Factors influencing sexual function in patients with rectal cancer.

Only few studies have investigated the impact of surgery for rectal cancer on sexual function. Little of that research included quality of life (QoL) aspects and hardly any study analyzed the impact of age, gender and type of surgery on sexual function. The aim of the presented study was to address these issues. Over a 5 y period, EORTC-QLQ-C-30 and a tumor-specific module were prospectively administered to patients before surgery, at discharge, 3, 6, 12 and 24 months postoperatively. Comparisons were made between patients receiving abdominoperineal resection (APR), anterior resection (AR) with or without Pouch and Sigmoid resection. Furthermore, effects of surgery on female and male patients, and age groups were analyzed. A total of 819 patients participated in the study: 412 were males and 407 were females. The groups were comparable in terms of adjuvant treatment, tumor stage and histology. Patients after APR and AR with Pouch had worst sexual function. Men reported significantly more difficulties with sexual enjoyment; furthermore, over time, sexual problems created high levels of strain in men that were worse than baseline levels in the early postoperative period. These problems tended to remain. Patients aged 69 y and younger scored higher for problems with loss of sexual function and sexuality-related strain than patients aged 70 y and older. The findings in this study confirm that QoL changes postsurgery and that factors like type of surgery, gender and age have tremendous impact on sexual function and sexual enjoyment. APR and AR with Pouch affect sexual function more than AR and resection of the lower sigmoid. Through impaired sexual enjoyment, men are put more under strain than women. Patients aged 69 y and younger experience more stress through deteriorated sexual function.

Surface modification of neural electrodes with pyrrole-hyaluronic acid conjugate to attenuate reactive astrogliosis in vivo.

Surface of neural probes were electrochemically modified with a non-cell adhesive and biocompatible conjugate, pyrrole-hyaluronic acid (PyHA), to reduce reactive astrogliosis. Poly(PyHA)-modified wire electrodes were implanted into rat motor cortices for three weeks and were found to markedly reduce the expression of glial fibrillary acidic protein compared to uncoated electrodes.

Gelsolin overexpression enhances neurite outgrowth in PC12 cells.

The rational design of therapies for treating nerve injuries requires an understanding of the mechanisms underlying neurite extension. Neurite motility is driven by actin polymerization; however, the mechanisms are not clearly understood. One actin accessory protein, gelsolin, is involved with remodeling the cytoskeleton, although its role in cell motility is unclear. We report a two-fold upregulation of gelsolin upon differentiation with nerve growth factor. Cells that were genetically modified to overexpress gelsolin have longer neurites and a greater neurite motility rate compared to controls. These data suggest that gelsolin plays an important role in neurite outgrowth.