The adaptive immune response to porous regenerated keratin as a bone graft substitute in an ovine model.

Reconstituted keratin is a novel bone graft material when prepared as a rigid scaffold. Understanding the immunogenicity of this material is important to determine whether this substance is a viable surgical option. Previous studies have shown no innate immune system activation in response to reconstituted keratin implants. To examine antibody-mediated immune responses to reconstituted keratin implants, bone and blood samples were taken from twelve sheep with surgically created tibial defects containing such implants. RT-PCR was used to detect mRNA of the inflammatory marker SOCS 3 in local bony tissue, and a novel immunohistochemistry assay developed to detect antikeratin antibodies in serum. Two animals were sacrificed per time-point at weeks 1, 2, 4, 6, 8 and 12. Time points for serum analysis included baseline (pre-surgery) and all other time points; mRNA analysis examined samples from all time points. No upregulation in antikeratin antibodies or SOCS 3 mRNA was observed at any time point, indicating that reconstituted keratin implants do not trigger an adaptive immune response in vivo in an ovine model. These findings provide the platform for further development of keratin implants in other mammalian models to define its immunogenic profile and safety.

Nissen Fundoplication-Preserving Laparoscopic Sleeve Gastrectomy.

Gastroesophageal reflux disease (GERD) is significantly more prevalent in obese patients. Nissen fundoplication alleviates symptoms in those refractory to dietary changes and optimal medical management. The need for concomitant treatment of GERD and obesity is becoming more prevalent. The objective of this study was to determine whether Nissen-preserving laparoscopic sleeve gastrectomy (SG) is a safe and effective weight loss option for patients with pre-existing Nissen fundoplication. The study was conducted at the Hospital Corporation of America, Memorial Health, Savannah, Georgia, academic institution. We retrospectively reviewed five patients who underwent laparoscopic Nissen-preserving SG between 2011 and 2017. We compared pre- and postoperative subjective GERD symptoms, occurrence of any immediate postoperative complications, change in BMI, and excess weight loss. Of the five patients, four were female and one was male. The mean age was 50.6 years. The mean preoperative BMI was 44.8 ± 5.4, one-month postoperative BMI was 41.2 ± 6.1 (P < 0.001), and six-month postoperative BMI was 37.5 ± 8.1 (P < 0.009), with mean excess weight loss at six months of 33.9 ± 23 per cent. There were no immediate postoperative complications. Subjective GERD symptoms were unchanged in two patients and improved in the other three. We demonstrate the early feasibility of Nissen-preserving SG for surgical weight loss in patients with existing Nissen fundoplication. Although our results are early, we feel encouraged by mean excess weight loss to date and control of GERD symptoms.

α-galactosidase A deficiency promotes von Willebrand factor secretion in models of Fabry disease.

Fabry disease results from loss of activity of the lysosomal enzyme α-galactosidase A (GLA), leading to the accumulation of globoseries glycosphingolipids in vascular endothelial cells. Thrombosis and stroke are life-threatening complications of Fabry disease; however, the mechanism of the vasculopathy remains unclear. We explored the relationship between GLA deficiency and endothelial cell von Willebrand factor (VWF) secretion in in vivo and in vitro models of Fabry disease. Plasma VWF was significantly higher at two months and increased with age in Gla-null compared to wild-type mice. Disruption of GLA in a human endothelial cell line by siRNA and CRISPR/Cas9 resulted in a 3-fold and 5-fold increase in VWF secretion, respectively. The increase in VWF levels was associated with decreased endothelial nitric oxide synthase (eNOS) activity in both in vitro models. Pharmacological approaches that increase nitric oxide bioavailability or decrease reactive oxygen species completely normalized the elevated VWF secretion in GLA deficient cells. In contrast, the abnormality was not readily reversed by recombinant human GLA or by inhibition of glycosphingolipid synthesis with eliglustat. These results suggest that GLA deficiency promotes VWF secretion through eNOS dysregulation, which may contribute to the vasculopathy of Fabry disease.

Use of a keratin-based wound dressing in the management of wounds in a patient with recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa is a rare, autosomal recessive blistering condition. The authors successfully treated a patient with a novel keratin-based dressing. Starting at 11 months, 1 hand and 1 foot of the patient was treated, and significant improvement was observed. Thereafter, keratin treatment was applied to both hands and feet.

Keratin-hydroxyapatite composites: biocompatibility, osseointegration, and physical properties in an ovine model.

Reconstituted keratin has shown promise as an orthopaedic biomaterial. This in vivo study investigates the biological response of composite materials prepared from reconstituted keratin containing a high content of hydroxyapatite (HA) (40 wt % HA), implanted for up to 18 weeks in the long bones of sheep. Keratin-HA composites were compared with a commercially available polylactic acid (PLA) HA composite (BIO RCI HA®, Smith and Nephew). Porous keratin-HA materials displayed excellent biocompatibility and osseointegration, with full integration into bone by 12 weeks. Dense keratin-HA materials also showed excellent biocompatibility, with a more limited osseointegration, involving the penetration of new bone into the periphery of the implant after eight weeks. In contrast, the PLA-HA implant did not integrate with surrounding tissue. Microindentation showed that porous keratin-HA implants were initially soft, but became stiffer as new bone penetrated the implant from four weeks onwards. In contrast, although the initial rigidity of dense keratin-HA composites was maintained for at least two weeks, the implant material weakened after four weeks. The PLA-HA implant maintained its physical properties throughout the course of the trial. This study demonstrates the increased osseointegration/osteoconduction capacity of keratin-HA composites and provides further evidence supporting the suitability of keratin-based materials, such as bone graft substitutes and soft tissue fixation devices.

Biocompatibility and osseointegration of reconstituted keratin in an ovine model.

Reconstituted keratin has potential as a raw material for orthopaedic applications. The aim of this study was to investigate the in vivo biocompatibility and osseointegration of keratin materials in an ovine model. Six different modifications of the keratin polymer, based on porous or dense constructs, regenerated by either neutral or acidic treatment, with or without hydroxyapatite, were made as small rods and inserted into drilled round defects in the femur and tibia of sheep. Histology was carried out on samples taken at different time points up to 24 weeks postsurgery. All keratin implants showed similar histological profiles, which included granulation tissue surrounding and infiltrating the implants, followed by new bone formation radiating from the existing bone. By 8 weeks, new bone had grown to within a short distance of the implant surface, and in some places was in direct apposition to the keratin implant. In the 12 to 24-week period, there was peripheral resorption and infiltration of bony trabeculae with regard to the porous constructs only. The tissue reaction appeared to model that of a fairly inert material. Further work on improving the extent of osseointegration and acceleration of the biodegradation rate of reconstituted keratin is underway.

Tissue reaction to matrices of reconstituted keratin polymer implanted subcutaneously in sheep.

Four different modifications of the keratin polymer were made as small rods and inserted into the subcutaneous tissue of the hind limbs of adult female sheep. Material 1 was porous, whereas materials 2, 3, and 4 had little or no internal porosity. The tissue response to each material was determined with regard to the extent of the inflammatory reaction and formation of a fibrous capsule around the implant, and the integrity and morphological appearance of the implant was assessed. An inflammatory cell infiltrate and fibrous capsule formed at an early stage around implants of material 1. Subsequently the inflammation decreased, the fibrous capsule became more mature, and the implants became cavitated and invaded by mono- and multi-nucleated macrophages, fibroblasts and blood vessels, with breakdown of the implant material occurring at its periphery. Similar changes were observed for implants made of materials 2 and 4. Implants of material 3 were remarkable in that, while surrounded by an inflammatory infiltrate and a fibrous capsule, they did not show any disturbance even at 24 weeks. The fibrous capsule around material 3 was thinner than that around material 1 at 6 to 24 weeks (both materials prepared using ammonium thioglycollate). No difference in capsule thickness was found for materials 2 and 4 (both materials prepared using thioglycollic acid).

Effect of the night float system on operative case volume for senior surgical residents.

PURPOSE: In response to the Accreditation Council for Graduate Medical Education (ACGME) mandated 80-hour workweek, the night float coverage model was one system created to comply with the work-hour restriction. However, concern has risen as to the operative case volume achieved with this model. The purpose of this study is to determine which system of call (night float vs traditional rotating call) provided the senior surgical resident with the greatest surgical case volume while in compliance with the 80-hour workweek. METHODS: A nonrandomized sequential study to evaluate the ACGME surgical operative logs (SOLs) for surgical chief residents at Memorial University Medical Center (MUMC), which is a level 1 trauma center, from 2006 to 2008 was conducted. The night float system (NFS) consisted of a PGY-4 or -5 assigned to in-house general surgery and trauma call from 6:00 pm to 6:00 am Monday through Friday morning and a 24-hour shift from 6:00 am on Sunday to 6:00 am Monday morning. Two months of night call rotations (nights) are performed each year per resident with the other 10 months devoted to daytime rotations (days). Conversely, the traditional rotating call schedule (TCS) placed each resident on-call every sixth night for a 30-hour period. The TCS required the resident to average approximately 3 weekday and 2 weekend calls per month. The data examined include all cases on the ACGME SOL submitted by each PGY-4 and 5 residents over a 2-year span. Specific designation of cases between night and day rotations was evaluated while on the NFS, and the total cases volume performed on the NFS and the TCS were analyzed. RESULTS: An evaluation of the 2006-2007 (NFS) year demonstrates an average of 16 cases per month while on nights as compared with 20 cases per month while on day rotations. The caseload on the night rotation was less than day rotations at the PGY-4/5 level. An analysis of the 2006-2007 (NFS) and 2007-2008 (TCS) for PGY-4/5 residents revealed an average total caseload of 224 and 276, respectively. A statistically significant total case difference of 52 cases over the entire year between the 2 systems of call was appreciated. CONCLUSIONS: Because of the work-hour restrictions, maximizing surgical education has become a necessity. With the various call systems used throughout general surgery programs, this study specifically compares a traditional 1-in-6 call schedule versus an NFS. Senior residents lost significant operative experience while operating under an NFS as compared with a TCS. Evidence suggests that the more hours spent by a chief resident during normal operative time elicits more operative experience.

Age differences in sexual partners and risk of HIV-1 infection in rural Uganda.

OBJECTIVES: To assess whether differences in age between sexual partners affect the risk of HIV infection in female adolescents and young adults. METHODS: A total of 6177 ever sexually active women aged 15 to 29 years completed a sociodemographic and sexual behavior questionnaire and provided a blood sample for HIV-1 serology. The age difference between partners was categorized as men 0 to 4 years older (referent group), 5 to 9 years older and 10 or more years older. HIV prevalence and incidence were assessed, and adjusted RR was estimated by multivariate regression. RESULTS: Prevalent HIV-1 infection in female participants increased with older male sexual partners. Among women aged 15 to 19 years, the adjusted risk of HIV infection doubled (RR = 2.04; 95% CI: 1.29-3.22) among those reporting male partners 10 or more years older compared with those with male partners 0 to 4 years older; among women 20 to 24 years of age, the RR was 1.24 (95% CI: 0.96-1.60). The attributable fraction (exposed) of prevalent HIV infection in women aged 15 to 24 years associated with partners 10 or more years older was 9.7% (95% CI: 5.2-14.0). HIV incidence did not increase with differences in age of partners. CONCLUSION: The age difference between young women and their male partners is a significant HIV risk factor, suggesting that high HIV prevalence in younger women is caused, in part, by transmission from older male partners.

Effects of mother-son incest and positive perceptions of sexual abuse experiences on the psychosocial adjustment of clinic-referred men.

OBJECTIVE: The primary objective was to examine the long-term impact of mother-son incest and positive initial perceptions of sexual abuse experiences on adult male psychosocial functioning. METHOD: Sixty-seven clinic-referred men with a history of sexual abuse participated. The participants completed self-report measures regarding their current psychosocial functioning and described the nature of their sexual and physical abuse experiences during childhood. RESULTS: Seventeen men reported mother-son incest, and these men endorsed more trauma symptoms than did other sexually abused men, even after controlling for a history of multiple perpetrators and physical abuse. Mother-son incest was likely to be subtle, involving behaviors that may be difficult to distinguish from normal caregiving (e.g., genital touching), despite the potentially serious long-term consequences. Twenty-seven men recalled positive or mixed initial perceptions of the abuse, including about half of the men who had been abused by their mothers. These men reported more adjustment problems than did men who recalled purely negative initial perceptions. CONCLUSIONS: Mother-son incest and positive initial perceptions of sexual abuse experiences both appear to be risk factors for more severe psychosocial adjustment problems among clinic-referred men.