A comparative evaluation of iliac crest bone graft with and without injectable and advanced platelet rich fibrin in secondary alveolar bone grafting for cleft alveolus in unilateral cleft lip and palate patients: A randomized prospective study.

PURPOSE: Platelet rich fibrin enhances bone healing and results in better graft intake and helps in faster periodontal healing. In this study we have used a combination of two newly developed forms of platelet rich fibrin: injectable and advanced along with iliac bone graft for secondary alveolar bone grafting and compared it with cases in which only iliac bone graft was used. METHODS: 30 patients with alveolar cleft, with age group of ≥7 years, having complete unilateral cleft alveolus were included and divided into 2 groups of 15 patients each randomly. In Group A, secondary alveolar bone grafting was done using iliac bone graft along with injectable and advanced palate rich fibrin and in Group B, secondary alveolar bone grafting was done only with iliac bone graft. Success of the treatment was assessed using radiographic and clinical methods which included: The bone resorption of the interalveolar septum height of the teeth adjacent to the cleft, evaluated as per Bergland classification, assessment of periodontal status of the teeth adjacent to cleft alveolus. RESULTS: After 3 months and 6 months postoperatively: study group had better overall scores as per Bergland criteria. Periodontal status improved in both groups but was more in study group compared to control group. For both evaluations the data was clinically favorable in the study group. CONCLUSION: On preliminary investigations it shows that combination of injectable and advanced platelet rich fibrin seems to enhance bone formation in alveolar clefts when admixed with autologous cancellous bone harvested from the iliac crest than using iliac bone graft alone. It also reduces the chances of bone resorption and show higher percentage of bone volume. Secondary alveolar grafting improves periodontal health around the cleft alveolus.

Comparison of efficacy of sodium hyaluronate and normal saline arthrocentesis in the management of internal derangement of temporomandibular joints - A prospective study.

PURPOSE: The aim of the present study was to evaluate the efficacy of arthrocentesis with and without sodium hyaluronate (SH) injection in the treatment of patients with temporomandibular joint (TMJ) internal derangement. MATERIALS AND METHODS: The study consisted of 20 patients with chief complaints of limited mouth opening, TMJ pain, and jaw deviation. Patients with disc displacement with reduction and closed lock were randomly divided into two groups. In Group 1, only arthrocentesis was performed, and in Group 2, arthrocentesis plus intra-articular injection of SH was performed. Arthrocentesis was performed under aseptic conditions using normal saline. Clinical evaluation was done for maximum mouth opening (MMO), TMJ pain, and jaw deviation before the procedure and 1 week, 2 weeks, 1 month, and 3 months following arthrocentesis. RESULTS: The mean visual analog scale (VAS) score change was statistically significant in Group 1 and Group 2 for within the group analysis. There was statistically significant difference in VAS score between Group 1 and Group 2 at all time intervals postoperatively. The increase in MMO from preoperative to 3 months postoperatively was statistically significant for within the group analysis. There was a reduction in mandibular deviation in both Group 1 and Group 2, but the difference was not statistically significant. There was no statistically significant difference in deviation between the two groups. CONCLUSION: Arthrocentesis with SH is superior to arthrocentesis alone in treating patients suffering with TMJ internal derangement, who are refractory to conservative treatment.

Evaluation of the Sternoclavicular Graft for the Reconstruction of Temporomandibular Joint After Gap Arthroplasty.

INTRODUCTION: Ankylosis may be defined as the fusion of the articular surfaces with bony or fibrous tissue. The treatment of temporomandibular joint ankylosis poses a significant challenge because of the high incidence of recurrence. A number of interpositional materials have been used including alloplastic materials (acrylic, proplast-teflon, silastic), and autogenous tissues (temporalis muscle flaps, buccal fat pad, dermis, costochondral grafts, metatarsal, fibula, tibia, iliac crest, cranial bone and Sternoclavicular graft SCG and cartilage). Literature suggests that rather than growth centre, we need adaptive centre. SCG is presumed to be a more suitable material for interpositional arthroplasty because Sternoclavicular Joint (SCJ) and TMJ are very similar developmentally, histologically and morphologically throughout the growth period. MATERIAL AND METHOD: Patients with TMJ ankylosis (8 males, 2 females) underwent release of the ankylosed joint by the senior author, between June 2013 and Novemeber 2015. The age of the patients ranged from 10 to 19 years. Pre- and post- operative assessment included a thorough history and physical examination to determine the cause of ankylosis, the maximal incisal opening, etiology and type of the ankylosis, recurrence rate. RESULT: MIO at 6 months follow up was 37.4±2.633 mm (range 32-40 mm), greater than MIO achieved in immediate postoperatively {34.4±2.22 mm (range 30-38 mm). After reconstruction of temporomandibular joint with sternoclavicular graft in the growing child there was a significant increase in the growth of mandible which was stunned due to ankylosis. And the ramal height also increased. CONCLUSION: The articular reconstruction with alloplastic or autogenous grafts, or gap arthroplasty for the treatment of ankylosis is shown to be efficient in relation to the post-operative maximal incisal opening, recurrence and articular function.

Evaluating the use of octyl-2-cyanoacrylate in unilateral cleft lip repair.

BACKGROUND: Facial cosmetic results are one of the most concerning issues for the parents who get their children operated for cleft lip. Moreover, the postoperative care of the surgical site, the discomfort associated with the suture removal, and additional visit for suture removal are other reasons which encourages one to use any new technologies that may replace the need for suture placement. In this study, we used octyl-2-cyanoacrylate, a tissue adhesive which offers a viable alternative to traditional techniques without compromising optimal wound closure. OBJECTIVE: To perform a comprehensive comparison of the outcomes from the use of Dermabond in patients undergoing primary repair of congenital cleft lip ± palate anomalies. MATERIALS AND METHODS: Twenty patients, in the age group of 3-18 months were treated surgically for unilateral cleft lip deformity using Millard rotation-advancement flap. Pre- and post-operative photographs of the patients were taken at 1 week, 2 week, 1 month, 6 months, and 1 year postoperatively and were evaluated using Vancouver scar scale which was given by Sullivan in 1990. Paired t-test was used for statistical analysis. RESULTS: Increased vascularity (hyperemia) was seen in the 1st and 2nd week in 35% and 30% patients, respectively which gradually reduced to normal in subsequent follow-ups. The scar was flat in 85% of patients in 1st week, and the number decreased to 10% at the end of 1 year. No wound dehiscence was found in any patients. Statistical analysis showed that among all the follow-ups, only the difference between the first and second follow-ups. Comparison of the results of 1 week with all other follow-ups yielded no significant results. CONCLUSION: Octyl-2-cyanoacrylate can be used for cleft lip closure effectively. The procedure is relatively painless and quick. Added to this are benefits of protection from wound infection since the material is bacteriostatic.

6-0 nylon versus 6-0 vicryl rapide in chieloplasty.

CONTEXT: Facial cosmetic result is one of the most concerning issues for the parents who get their children operated for cleft lip. Moreover, the discomfort associated with the suture removal encourages one to use any new technology that may replace the need for suture placement. The type of suture material used in surgery has been a long-standing debate among surgeons. In this study, we compared rapidly absorbable suture material (Vicryl Rapide™) with nonabsorbable suture material (nylon). AIMS: The aim of this study is to compare the appearance and course of scar, wound infection, and patient's parent perception using Vicryl Rapide and nylon in nonsyndromic congenital cleft lip repair. SETTINGS AND DESIGN: This was a randomized prospective controlled clinical trial. MATERIALS AND METHODS: Twenty patients, in the age group of 3-18 months treated for unilateral congenital cleft lip deformity, were included and randomly allocated to two groups with ten patients each. Skin suturing was done with 6-0 polyamide and 6-0 irradiated polyglactin in Groups A and B, respectively. Patients were evaluated at 1 week, 1, 3, 6 months, and 1 year postoperatively in person by the observer as well as by the patient's parent. STATISTICAL ANALYSIS USED: Descriptive statistical analysis was done using SPSS 20, and Student's t-test was applied. RESULTS: It was found that Vicryl Rapide showed more hypopigmented scars and raised scars than nylon at the end of 1 year though overall appearance was comparable between the groups. CONCLUSIONS: Vicryl Rapide showed poorer cosmetic outcomes in terms of height and pigmentation of car as compared to nylon suture of same thickness. However, since scars tend to improve with time, a bigger sample size and a longer follow-up are required to generalize this statement.

Elucidation of the structure of retroviral proteases: a reminiscence.

Determinations of only a very few protein structures had consequences comparable to the impact exerted by the structure of the protease encoded by HIV-1, published just over 25 years ago. The structure of this relatively small protein and its cousins from other retroviruses provided a clear target for a spectacularly successful structure-assisted drug design effort that offered new hope for controlling the then-escalating AIDS epidemic. This reminiscence is limited primarily to work conducted at the National Cancer Institute, and is not meant to be a comprehensive history of the field, but is rather an attempt to provide a very personal account of how the structures of this most thoroughly studied crystallographic target were determined.

Assessment of facial nerve injury with "House and Brackmann facial nerve grading system" in patients of temporomandibular joint ankylosis operated using deep subfascial approach.

BACKGROUND: Preservation of the functional integrity of the facial nerve (FN) is a critical measure of success in temporomandibular joint (TMJ) surgery. In spite of the development of a myriad of surgical approaches to the TMJ, FN remains at risk. The deep subfascial approach provides an additional layer of protection (the deep layer of the temporalis fascia and the superficial temporal fat pad) to the temporal and zygomatic branches of the FN and thus, is the safest method to avoid FN injury. OBJECTIVES: To assess FN injury following TMJ surgery using deep subfascial approach and measuring it on House and Brackman facial nerve grading system (HBFNGS). MATERIALS AND METHODS: Twenty TMJs in 18 patients were operated for TMJ ankylosis, using "the deep subfascial approach." FN function was assessed postoperatively at 24 h, 1 week, 1 month, 3 months, 6 months using HBFNGS. Statistical analysis was done using SPSS 16.0. RESULTS: Of 20 surgical sites 3 sites showed Grade III (moderate) FN injury and 17 sites showed Grade II (mild) FN injury at 24 h. The condition improved with time with full recovery of FN at all surgical sites at 6 months. CONCLUSION: The deep subfascial approach has a distinct advantage over the conventional approaches when dissecting the temporal region and is the safest method to avoid injury to FN.

Evaluation of Retro Mandibular Approach to Open Reduction and Internal Fixation of Condylar Fractures: A Cross-sectional Study.

PURPOSE: The present study was carried out to evaluate the usefulness of mini retromandibular approach on accessibility, scarring and stability in open reduction and internal fixation of sub condylar fractures. MATERIALS AND METHODS: Fifteen patients underwent open reduction and rigid fixation of middle and low subcondylar fractures, with mini-retro mandibular approach. RESULTS: No signs of infection were observed in any patient postoperatively. Surgical scar was imperceptible and esthetically acceptable in all the cases. Out of 15 patients, only one patient had discrepancy in occlusion and after 2 months satisfactory centric occlusion was achieved. Salivary fistula (parotid fistula) was observed in 3 cases within 1 week postoperatively, which was treated spontaneously with the use of hypertonic saline. Transient facial nerve weakness was observed in 2 patients, in one patient it resolved in 4 weeks postoperatively and in second patient 3 months postoperatively. Mouth opening increased in all the patients with time. Average mouth opening at 1 week interval was 19.6 mm, at 2 months interval 28.2 mm, and after 6 months 38.33 mm suggesting that mouth opening gradually increased with time. At the end of 2 months postoperatively none of the patients had any restriction in lateral movements. At 2 months postoperatively 4 patients had deviation but none of the patients had any deviation 6 months postoperatively. CONCLUSION: It is evident from the results of our study that open reduction and internal fixation using mini-retromandibular approach is good treatment option in management of mandibular condylar fractures.

Comparative study of 2 palatoplasty techniques to assess speech and fistula in primary cleft palate patients.

PURPOSE: To assess the Quality of speech and the incidence of post operative fistula in each technique after 6 months follow up study. METHODS: This prospective study consists of 24 patients in the age group of 18 to 36 months, male 12 and female 12. All the patients were divided into two groups-Group I-12 patients for two layer closure, Group II-12 patients for three layer closure. Exclusion criteria was submucous clefts, any identified syndrome and patients with hearing loss. All the patients have undergone pre-operative speech assessment by the speech therapist. At end of 6 months, speech analysis was done based on three parameters, i.e. nasality (A), Articulation (B) and intelligibility (C). RESULTS: Patients with radical muscle dissection (three layer) group had statistically significant (P=0.023) improvement in nasal resonance compared to the conservative technique (two layer) in the younger age group. But there was no statistically significant difference in the articulation and the intelligibility of speech. CONCLUSION: Radical dissection and palatal muscle reconstruction confers better functional results regarding nasal resonanace, especially in younger age group. Quality of speech in the elder group, patients 25-36 months old in both the technique groups was almost the same. The incidence of fistula was slightly more in the radical dissection group.

Management of parotid fistula using hypertonic saline.

Parotid fistula is a very rare, unpleasant and painful complication following surgery in the maxillofacial region. Although there is consensus in the literature that acute parotid injury must be explored primarily and all injured structures be repaired accurately, the treatment of the chronic injury is controversial. Numerous methods of treatment, conservative as well as aggressive, have been described with varying success and morbidity. This paper presents a simple but effective and conservative method of treating this complication with the use of hot hypertonic saline.

Esthetic correction of depressed frontal bone fracture.

Depressed frontal bone fractures are occasionally seen in maxillofacial trauma patient. If untreated, they look un-esthetic. Although there are numerous options available for correction of these defects, use of bone cement (polymethylmethacrylate or PMMA) is simple and reliable. This is the report of one such case.

Visit-specific expectations and patient-centered outcomes: a literature review.

BACKGROUND: Primary care patients often have certain expectations when visiting physicians, many of which may be undetected. These unmet expectations can affect outcomes such as satisfaction with care. We performed a formal literature review to examine the effect of fulfillment of patients' visit-specific expectations on their satisfaction as well as on health status and compliance. PATIENTS AND METHODS: Included studies were conducted in primary care settings, systematically recruited patients, elicited previsit and/or postvisit expectations relative to specific visits, and measured patient-centered outcomes. Two reviewers abstracted information on study characteristics; types, timing, and method of expectation ascertainment; and outcomes. Disagreements were resolved by consensus. RESULTS: Twenty-three studies were reviewed including 7 trials, 4 cohort studies, and 12 cross-sectional studies. Patients frequently expected information rather than specific physician actions, but physicians often did not accurately perceive patients' visit-specific expectations. In 19 studies that assessed postvisit patient satisfaction, a positive association between meeting patient expectations and overall satisfaction was demonstrated in 11 studies, inconclusive in 3, and not established in 5. In 2 studies assessing physician satisfaction, physicians with access to patients' expectations were more satisfied than those without access. Other outcomes (symptom or disease improvement, health status, test ordering, health care costs, psychological symptoms) were measured in only a few studies, and the results were inconclusive. CONCLUSIONS: Addressing patients' visit-specific expectations appears to affect satisfaction to a modest degree. Future studies should evaluate methods that efficiently elicit, prioritize, and provide patients' previsit expectations for physicians and should examine the longitudinal effect of expectation fulfillment on patient outcomes. Arch Fam Med. 2000;9:1148-1155

Age-related hippocampal changes in Bcl-2:Bax ratio, oxidative stress, redox-active iron and apoptosis associated with aluminum-induced neurodegeneration: increased susceptibility with aging.

We propose that aging is an important factor in the susceptibility of neurons to oxidative stress and to subsequent apoptosis. In the present report we demonstrate that aged rabbits treated intracisternally with aluminum maltolate exhibit intense intraneuronal silver positivity indicative of the formation of neurofilamentous aggregates, together with oxidative stress. These changes occur in the CA1 region of the hippocampus as well as in cerebral cortical areas. Apoptosis, measured by the TUNEL in situ technique, colocalizes with oxidative stress. Young animals treated with aluminum show few of these alterations, while age-matched controls are essentially negative. Further studies on the time course of these and related changes demonstrate that oxidative stress and redox-active iron accumulation in hippocampal neurons occur very rapidly, within a period of 3 hours, and increased in intensity at 72 hours. Changes suggestive of apoptosis are seen by 24 hours and are pronounced at 72 hours. In aged animals there is an initially intense immunopositivity at 3 hours for Bcl-2, with negative staining for Bax. By 72 hours, when apoptosis is strongly evident, Bcl-2 is negative and Bax strongly positive. In contrast to the aged rabbits, young animals treated similarly with aluminum exhibit much less oxidative stress with no apoptosis, and maintain Bcl-2 immunopositivity and negative Bax staining. Our findings strongly support the key role that oxidative damage plays in the process of neurodegeneration and in the increased vulnerability to aluminum-induced injury in the aged animal. These are novel observations which may have important implications for aiding in our understanding of the pathogenesis of neurodegeneration occurring in Alzheimer's disease.

Use of complementary therapies for arthritis among patients of rheumatologists.

BACKGROUND: Use of complementary and alternative medicine (CAM) is common among persons with chronic conditions. OBJECTIVE: To identify correlates of and describe patients' perspective on use of CAM for rheumatologic conditions. DESIGN: Telephone survey. SETTING: Three university practices and three private rheumatology practices. PATIENTS: 232 of 428 eligible consecutive patients (54%) with scheduled appointments. MEASUREMENTS: Patients answered questions on CAM use, functional status, pain, provider satisfaction, and health services utilization. Chart reviews provided demographic information and rheumatologic diagnoses. Bivariate analyses identified correlates of four CAM outcomes (history, magnitude, and frequency of CAM use and communication about CAM use with a physician), and multiple logistic regression identified independent correlates of regular CAM use. RESULTS: Approximately two thirds of the respondents (n = 146) had used CAM. Of these 146 respondents, 82 (56%) currently used CAM and 132 (90%) regularly used CAM or had done so in the past. Fifty-five respondents (24%) had used three or more types of CAM. In multivariate analyses, persons who used CAM regularly were more likely to have osteoarthritis (odds ratio, 5.6 [95% CI, 1.9 to 16.8]), severe pain (odds ratio, 2.5 [CI, 1.4 to 4.8]), and a college degree (odds ratio, 2.6 [CI, 1.3 to 5.4]) than patients who had never used CAM. Nearly half of the respondents discussed CAM use with their physicians. The most common reasons for not disclosing CAM use were that the physician had not asked about it and that the patient forgot to tell the physician; fear of disapproval was rarely cited. Discussions about CAM use between patient and physician occurred more frequently among patients with fibromyalgia and persons who regularly used CAM or used several types of CAM. CONCLUSIONS: Patients with rheumatologic conditions frequently use CAM. Severe pain and osteoarthritis predict regular use of CAM but do not predict a greater likelihood of discussing CAM use with physicians. Routine inquiry by physicians will probably detect CAM use.

Crystal structure of rabbit muscle creatine kinase.

The crystal structure of rabbit muscle creatine kinase, solved at 2.35 A resolution by X-ray diffraction methods, clearly identified the active site with bound sulfates surrounded by a constellation of arginine residues. The putative binding site of creatine, which is occupied by a sulfate group in this analysis, has been tentatively identified. The dimeric interface of the enzyme is held together by a small number of hydrogen bonds.

Using focus groups to understand arthritis patients' perceptions about unconventional therapy.

OBJECTIVE: To understand arthritis patients' use of unconventional therapies (UT). METHODS: Thirty-three rheumatoid arthritis and osteoarthritis patients followed in university clinics participated in 5 focus groups to discuss: their beliefs about arthritis and UT; UT they have used; reasons for using UT; effectiveness of UT; sources of information on UT; and communication about UT with the physician. Two investigators analyzed focus group transcripts to identify common themes. RESULTS: All patients believed arthritis to be incurable by conventional regimens or UT. Over one-half had used UT to relieve pain; cost was unimportant. Patients trusted information about UT from family, friends, and others with arthritis, but not supermarket tabloids or television commercials. Most discussed UT use with their physician, primarily to prevent interactions with prescribed treatments. Physicians' reactions ranged from ridicule to giving permission to continue using UT. CONCLUSIONS: These results provide an understanding of arthritis patients' motives for using UT and for discussing this behavior with their physician.

Limitations of the 1990 American College of Rheumatology classification criteria in the diagnosis of vasculitis.

BACKGROUND: The American College of Rheumatology (ACR) established criteria to discriminate among patients with seven types of vasculitis. Although designated as "classification criteria" for research, these criteria are often used for diagnosis. OBJECTIVE: To examine the operating characteristics of the 1990 ACR classification criteria in the diagnosis of Wegener granulomatosis, giant-cell arteritis, polyarteritis nodosa, and hypersensitivity vasculitis. DESIGN: Prospective cohort study. SETTING: University medical center and Veterans Affairs medical center. PATIENTS: 198 consecutive patients referred to rheumatologists for evaluation of possible vasculitis. MEASUREMENTS: Blinded chart audits were done to classify patients according to the 1990 ACR classification criteria for Wegener granulomatosis, polyarteritis nodosa, giant-cell arteritis, and hypersensitivity vasculitis on the basis of the patients' initial presentation. Chart audits done 2 to 8 months after baseline provided the patients' final diagnoses, which were considered the gold standard, as in the development of the ACR criteria. Test operating characteristics of the ACR classification criteria were calculated according to 2 x 2 tables for the entire cohort and for only the patients with a final diagnosis of vasculitis. RESULTS: Vasculitis was diagnosed in 51 (26%) patients. Thirty-eight (75%) of 51 patients with vasculitis and 31 (21%) of 147 patients without vasculitis met ACR criteria for one or more types of vasculitis. The positive predictive values for the four vasculitides according to ACR criteria were 17% to 29% for the entire cohort and 29% to 75% for only the patients with a final diagnosis of vasculitis. CONCLUSION: The 1990 ACR classification criteria function poorly in the diagnosis of specific vasculitides.

Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy.

OBJECTIVE: To determine whether treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate hydrochloride or pemoline diminishes the response to growth hormone (GH) therapy in patients with idiopathic GH deficiency (IGHD) or idiopathic short stature (ISS). METHODS: The National Cooperative Growth Study database was used to identify patients between 3 and 20 years of age with IGHD or ISS and those within these groups who were treated with methylphenidate or pemoline for ADHD. Their growth in response to GH treatment (change in height standard deviation score [SDS]) was compared with that of patients with IGHD or ISS who were not treated for ADHD, by using a stepwise multiple regression analysis. RESULTS: In the IGHD cohort, there were 184 patients who were being treated for ADHD and 2313 who were not. In the ISS cohort there were 117 patients who were being treated for ADHD and 1283 who were not. There was a higher percentage of males being treated for ADHD in both cohorts. In the IGHD cohort, the change in height SDS was positively associated with the number of years of GH treatment, parents' heights, body mass index, and GH injection schedule, and was negatively associated with height SDS at the initiation of GH therapy, age, and maximum stimulated GH level. The use of methylphenidate or pemoline had a negative effect on the change in height SDS, but the magnitude of the effect was small. Similar effects were noted in the ISS cohort, but body mass index and the use of methylphenidate or pemoline had no effect on the change in height SDS. CONCLUSIONS: Concurrent ADHD therapy is associated with a slight decrease in the change in height SDS during GH treatment in patients with IGHD but not in those with ISS. Even in IGHD, the magnitude of the effect is small and should not deter the use of such concurrent therapy.

Modifications to the in situ TUNEL method for detection of apoptosis in paraffin-embedded tissue sections.

The in situ detection of cells undergoing apoptosis is increasingly important in the analysis of injury and degeneration in the central nervous system. Limited information is presently available on the quantification of apoptosis in paraffin-embedded brain tissue sections, a technique which would be most useful in the evaluation of archival tissue for diagnostic and experimental purposes. In this report, optimized conditions for tissue digestion and permeabilization using Proteinase K and Triton X and a quantification method for apoptosis detection are described using brain sections from aluminum maltolate-treated aged and young rabbits as compared to untreated matched controls. This method provides optimal staining of apoptotic cells without the problem of tissue destruction, and should prove useful in evaluating the process of apoptosis in neurodegenerative disorders.

Experimental aluminum encephalomyelopathy. Relationship to human neurodegenerative disease.

Alzheimer's disease has a complex pathogenesis and is a devastating neurologic disorder, predominantly of the elderly human population. Neuronal cell loss and neuritic pathology are a major neuropathologic feature of Alzheimer's disease, but there is no established mechanism to explain the degenerative process. The development of suitable animal systems would be of great value in helping to understand the basic mechanisms underlying the disease. We propose that the aluminum maltolate-treated elderly rabbit is a potentially useful animal system to model Alzheimer's disease neurofibrillary pathology. Details of such an experimental aluminum encephalopathy produced in the rabbit are discussed, along with other aspects of aluminum-induced neurodegeneration.