Ligament augmentation and reconstruction system (LARS) synthetic grafts are safe and effective for medial collateral ligament and posterolateral corner reconstructions in elite athletes.

PURPOSE: This study documents the efficacy and safety of using a Ligament Augmentation and Reconstruction System (LARS) ligament graft to augment extra-articular knee ligament reconstructions in elite athletes by reporting return-to-play (RTP) rates and levels, career longevity and complications. METHODS: A consecutive series of all extra-articular knee ligament reconstructions augmented by LARS ligaments in elite athletes undertaken by three specialist sports knee surgeons between 2013 and 2020 were reviewed. Seventy-six elite athletes, aged over 16 years old, and more than 2 years postsurgery were included. RTP was defined as competing at professional level or national/international level in amateur sport. RESULTS: There were 64 medial collateral ligament (MCL) and 12 posterolateral corner (PLC) reconstructions. Fifty-two (68.4%) underwent concomitant autograft cruciate ligament(s) reconstruction. The mean age was 25.1 years (SD ± 4.5). Most were football (35, 46.1%) or rugby players (35, 46.1%). Sixty-seven athletes (88.2%) RTP with 65 (97.0%) of these playing at the same or higher Tegner level. Fifty-six (83.6%) of the athletes that RTP were still playing at 2 years postsurgery. Twenty (57.1%) of those who had RTP and were more than 5 years postsurgery were still playing at 5 years. Six (7.9%) players required further surgery relating to the LARS/metalwork. One case had soft tissue inflammation adjacent to the proximal end of the synthetic graft, but it is unknown if this was mechanical irritation or a biological reaction. One MCL reruptured 4 years after RTP. CONCLUSION: Utilising LARS to augment extra-articular knee ligament reconstructions allows 88.2% of athletes with a variety of knee ligament injuries to return to elite sport. The low morbidity rates coupled with 57% of athletes still playing 5 years postsurgery demonstrates that the LARS is safe and effective in these cases. Although there are reports of LARS ligaments being used in MCL and PLC reconstructions, there is very little evidence investigating if they are safe and effective. This study demonstrates that LARS synthetic grafts can be safely used for MCL and PLC reconstructions in elite athletes and they permit a high RTP with a low risk of complications. LEVEL OF EVIDENCE: Level IV.

Measurement of Murine Neuromuscular Function Using the In Situ Preparation.

The presence and progression of a neuromuscular pathology can impact on the contractile force production of a muscle. Hence, measurements of force production can be an important tool for the evaluation of disease progression. In this chapter, we describe how to perform in situ function testing on the tibialis anterior muscle using a murine model. Performing neuromuscular in situ function testing allows force measurements to be recorded in a physiologically relevant environment.

Association of cancer with comorbid inflammatory conditions and treatment in patients with Lynch syndrome.

BACKGROUND: Individuals with Lynch syndrome (LS) and hereditary non-polyposis colorectal cancer (HNPCC) are at increased risk of both colorectal cancer and other cancers. The interplay between immunosuppression, a comorbid inflammatory condition (CID), and HNPCC on cancer risk is unclear. AIM: To evaluate the impact of CIDs, and exposure to monoclonal antibodies and immunomodulators, on cancer risk in individuals with HNPCC. METHODS: Individuals prospectively followed in a hereditary cancer registry with LS/HNPCC with the diagnosis of inflammatory bowel disease or rheumatic disease were identified. We compared the proportion of patients with cancer in LS/HNPCC group with and without a CID. We also compared the proportion of patients who developed cancer following a CID diagnosis based upon exposure to immunosuppressive medications. RESULTS: A total of 21 patients with LS/HNPCC and a CID were compared to 43 patients with LS/HNPCC but no CID. Cancer occurred in 84.2% with a CID compared to 76.7% without a CID (P = 0.74) with no difference in age at first cancer diagnosis 45.5 ± 14.6 vs 43.8 ± 7.1 years (P = 0.67). LS specific cancers were diagnosed in 52.4% with a CID vs 44.2% without a CID (P = 0.54). Nine of 21 (42.9%) patients were exposed to biologics or immunomodulators for the treatment of their CID. Cancer after diagnosis of CID was seen in 7 (77.8%) of exposed individuals vs 5 (41.7%) individuals unexposed to biologics/immunomodulators (P = 0.18). All 7 exposed compared to 3/5 unexposed developed a LS specific cancer. The exposed and unexposed groups were followed for a median 10 years and 8.5 years, respectively. The hazard ratio for cancer with medication exposure was 1.59 (P = 0.43, 95%CI: 0.5-5.1). CONCLUSION: In patients with LS/HNPCC, the presence of a concurrent inflammatory condition, or use of immunosuppressive medication to treat the inflammatory condition, might not increase the rate of cancer occurrence in this limited study.

A High-End Estimate of Sea Level Rise for Practitioners.

Sea level rise (SLR) is a long-lasting consequence of climate change because global anthropogenic warming takes centuries to millennia to equilibrate for the deep ocean and ice sheets. SLR projections based on climate models support policy analysis, risk assessment and adaptation planning today, despite their large uncertainties. The central range of the SLR distribution is estimated by process-based models. However, risk-averse practitioners often require information about plausible future conditions that lie in the tails of the SLR distribution, which are poorly defined by existing models. Here, a community effort combining scientists and practitioners builds on a framework of discussing physical evidence to quantify high-end global SLR for practitioners. The approach is complementary to the IPCC AR6 report and provides further physically plausible high-end scenarios. High-end estimates for the different SLR components are developed for two climate scenarios at two timescales. For global warming of +2°C in 2100 (RCP2.6/SSP1-2.6) relative to pre-industrial values our high-end global SLR estimates are up to 0.9 m in 2100 and 2.5 m in 2300. Similarly, for a (RCP8.5/SSP5-8.5), we estimate up to 1.6 m in 2100 and up to 10.4 m in 2300. The large and growing differences between the scenarios beyond 2100 emphasize the long-term benefits of mitigation. However, even a modest 2°C warming may cause multi-meter SLR on centennial time scales with profound consequences for coastal areas. Earlier high-end assessments focused on instability mechanisms in Antarctica, while here we emphasize the importance of the timing of ice shelf collapse around Antarctica. This is highly uncertain due to low understanding of the driving processes. Hence both process understanding and emission scenario control high-end SLR.

Effects of foam rolling for delayed onset muscle soreness on loaded military task performance and perceived recovery.

OBJECTIVE: The purpose of this investigation was to evaluate the effects of foam rolling (FR) and passive recovery (PR) on symptoms of delayed-onset muscle soreness (DOMS) and military-specific performance. METHODS: Twenty men and women (age: 23.6 ± 4.1 years, height: 176.4 ± 5.6 cm, and body mass: 84.7 ± 13.4 kg) completed a DOMS-inducing exercise protocol (DIP), followed by FR or PR. Four loaded military tasks (LMT) were performed 24 h later. Rating of perceived exertion (RPE) was measured during DIP and after each LMT. Rating of muscle pain (RMP) was measured prior to the LMTs and after the recovery protocols. A repeated measure analysis of variance and partial eta squared were used to compare LMT performance across baseline, FR and PR sessions. Friedman tests compared perceptual variables across baseline, FR, and PR. Wilcoxon matched-pairs signed-ranks test evaluated RPE during DIP, post-DIP, and post-recovery RMP between FR and PR. RESULTS: LMT performance times were significantly faster after FR compared to PR (stair climb: p = .038, cover position sprint: p = .011, simulated ammunition can carry: p = .003, Shuttle Run: p = .034). RPE measured during LMTs was similar across all data points. Post-recovery RMP for FR (3.0 (2.3, 4.0)) and PR (4.0 (3.0, 6.0)) were not significantly different. CONCLUSION: FR reduced the impact of DOMS on three loaded tactical performance tasks without significant reduction in perceived soreness.

Surveillance pouchoscopy for dysplasia: Cleveland Clinic Ileoanal Pouch Anastomosis Database.

BACKGROUND: No formal guidelines exist for surveillance pouchoscopy following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. METHODS: All adults who had previously had IPAA for ulcerative colitis, and underwent a pouchoscopy between 1 January 2010 and 1 January 2020, were included. RESULTS: A total of 9398 pouchoscopy procedures were performed in 3672 patients. The majority of the examinations were diagnostic (8082, 86·0 per cent; 3260 patients) and the remainder were for routine surveillance (1316, 14·0 per cent; 412 patients). Thirteen patients (0·14 per cent of procedures) were found to have biopsy-proven neoplasia at the time of pouchoscopy; seven had low-grade dysplasia (LGD) (0·07 per cent; all located in the anal transition zone), none had high-grade dysplasia (HGD) and six (0·06 per cent) had invasive adenocarcinoma (4 in anal transition zone and 6 in pouch). Of the six patients with adenocarcinoma, four had neoplasia at the time of proctocolectomy (2 adenocarcinoma, 1 LGD, 1 HGD); all six were symptomatic with anal bleeding or pelvic pain at the time of pouchoscopy, had a negative surveillance pouchoscopy examination within 2 years of diagnosis of adenocarcinoma, had palpable masses on digital rectal examination, and had visible lesions at the time of pouchoscopy. CONCLUSION: Surveillance pouchoscopy is not recommended in asymptomatic patients because significant neoplasia following IPAA for ulcerative colitis is rare.

ANTECEDENTES: No existen unas recomendaciones formales para vigilancia endoscópica en pacientes a los que se les ha realizado un reservorio ileoanal (ileal pouch anal anastomosis, IPAA) por una colitis ulcerosa (ulcerative colitis, UC). MÉTODOS: Se incluyeron todos los pacientes adultos a los que se les había realizado previamente un IPAA por UC y se sometieron a una endoscopia del reservorio. RESULTADOS: Se realizaron un total de 9.398 procedimientos endoscópicos en 3.672 pacientes entre el 1/1/2010 y el 1/1/2020. La mayoría de las exploraciones fueron diagnósticas (n = 8.082; 86%; 3.260 pacientes) y el resto fueron de seguimiento (n = 1.316; 14%; 412 pacientes). Se descubrió que 13 pacientes tenían una neoplasia demostrada por biopsia (0,14%) en el momento de la endoscopia; siete pacientes tenían displasia de bajo grado (low-grade displasia, LGD) (0,074%; localizada en todos los casos en la zona de transición anal), ninguno tenía displasia de alto grado (high-grade displasia, HGD) y seis (0,064%) tenían un adenocarcinoma invasivo (cuatro en la zona de transición anal) y dos en el reservorio). De los seis pacientes con adenocarcinoma, 4 tenían neoplasia en el momento de la proctocolectomía (2 adenocarcinoma, uno LGD, uno HGD). Todos estos pacientes tenían síntomas de hemorragia anal o dolor pélvico en el momento de la endoscopia, se les había practicado una endoscopia previa reciente del reservorio en los dos años anteriores, presentaban una masa palpable en la exploración digital rectal, así como lesiones visibles en la endoscopia del reservorio. CONCLUSIÓN: La vigilancia endoscópica del reservorio no se recomienda en pacientes asintomáticos porque es raro que aparezca una neoplasia después del IPAA por UC.

The relationship between mesorectal grading and oncological outcome in rectal adenocarcinoma.

AIM: The prognostic association between mesorectal grading and oncological outcome in patients undergoing resection for rectal adenocarcinoma is controversial. The aim of this retrospective chart review was to determine the individual impact of mesorectal grading on rectal cancer outcomes. METHOD: We compared oncological outcomes in patients with complete, near-complete and incomplete mesorectum who underwent rectal excision with curative intent from 2009 to 2014 for Stage cI-III rectal adenocarcinoma. We also assessed the independent association of mesorectal grading and oncological outcome using multivariate models including other relevant variables. RESULTS: Out of 505 patients (339 men, median age of 60 years), 347 (69%) underwent a restorative procedure. There were 452 (89.5%), 33 (6.5%) and 20 (4%) patients with a complete, near-complete and incomplete mesorectum, respectively. Local recurrence was seen in 2.4% (n = 12) patients after a mean follow-up of 3.1 ± 1.7 years. Unadjusted 3-year Kaplan-Meier analysis by mesorectal grade showed decreased rates of overall, disease-free and cancer-specific survival and increased rates of overall and distant recurrence with a near-complete mesorectum, while local recurrence was increased in cases of an incomplete mesorectum (all P < 0.05). On multivariate analyses, a near-complete mesorectum was independently associated with decreased cancer-specific survival (hazard ratio 0.26, 95% CI 0.1-0.7; P = 0.007). There were no associations between mesorectal grading and overall survival, disease-free survival, overall recurrence or distant recurrence (all P > 0.05). CONCLUSION: Mesorectal grading is independently associated with oncological outcome. It provides unique information for optimizing surgical quality in rectal cancer.

Hypoxic preconditioning of myoblasts implanted in a tissue engineering chamber significantly increases local angiogenesis via upregulation of myoblast vascular endothelial growth factor-A expression and downregulation of miRNA-1, miRNA-206 and angiopoietin-1.

Vascularization is a major hurdle for growing three-dimensional tissue engineered constructs. This study investigated the mechanisms involved in hypoxic preconditioning of primary rat myoblasts in vitro and their influence on local angiogenesis postimplantation. Primary rat myoblast cultures were exposed to 90 min hypoxia at <1% oxygen followed by normoxia for 24 h. Real time (RT) polymerase chain reaction evaluation indicated that 90 min hypoxia resulted in significant downregulation of miR-1 and miR-206 (p < 0.05) and angiopoietin-1 (p < 0.05) with upregulation of vascular endothelial growth factor-A (VEGF-A; p < 0.05). The miR-1 and angiopoietin-1 responses remained significantly downregulated after a 24 h rest phase. In addition, direct inhibition of miR-206 in L6 myoblasts caused a significant increase in VEGF-A expression (p < 0.05), further establishing that changes in VEGF-A expression are influenced by miR-206. Of the myogenic genes examined, MyoD was significantly upregulated, only after 24 h rest (p < 0.05). Preconditioned or control myoblasts were implanted with Matrigel™ into isolated bilateral tissue engineering chambers incorporating a flow-through epigastric vascular pedicle in severe combined immunodeficiency mice and the chamber tissue harvested 14 days later. Chambers implanted with preconditioned myoblasts had a significantly increased percentage volume of blood vessels (p = 0.0325) compared with chambers implanted with control myoblasts. Hypoxic preconditioned myoblasts promote vascularization of constructs via VEGF upregulation and downregulation of angiopoietin-1, miR-1 and miR-206. The relatively simple strategy of hypoxic preconditioning of implanted cells - including non-stem cell types - has broad, future applications in tissue engineering of skeletal muscle and other tissues, as a technique to significantly increase implant site angiogenesis.

Colorectal surveillance after segmental resection for young-onset colorectal cancer: is there evidence for extended resection?

AIM: Although sporadic colorectal cancer (CRC) usually occurs in patients aged over 50, recent evidence suggests that the incidence is increasing in younger patients. Such patients are theoretically at high risk of metachronous neoplasia and may be candidates for extended prophylactic colectomy. This study aimed to define the risk of metachronous cancer/adenomas during follow-up of younger patients who underwent segmental colectomy for CRC. METHOD: A CRC database was used to identify patients aged under 50 who underwent surgery for CRC between 1994 and 2010. Patients diagnosed with hereditary cancer or inflammatory bowel disease were excluded. The primary end-points were frequency of extended resection and the rates of metachronous cancer and high-risk adenomas during follow-up. RESULTS: There were 284 young patients with a resectable primary tumour, of whom 280 (98.6%) underwent segmental resection, 3 (1%) extended resection and 1 (0.4%) local resection. Endoscopic follow-up was available for 150 of the patients who had segmental colectomy, with a mean age of 42.6 (±5.8) years at diagnosis and median follow-up time of 68 months (interquartile range 45-105). Out of these 150 patients, 4 (2.7%) developed metachronous colonic adenocarcinoma at 24, 71, 151 and 228 months after index surgery. Thirty additional patients had at least one adenoma identified during surveillance, and three had sessile serrated polyps. Out of the three patients undergoing extended resection, none had metachronous cancer or advanced adenomas at an average follow-up of 17 years. CONCLUSION: A segmental colectomy or proctectomy is adequate treatment for patients presenting with CRC under the age of 50.

Restorative proctocolectomy: an example of how surgery evolves in response to paradigm shifts in care.

AIM: Surgical technique constantly evolves in response to the pressure of progress. Ileal pouch anal anastomosis (IPAA) is a good example. We analysed the effect of changes in practice on the technique of IPAA and its outcomes. METHOD: Patients undergoing primary IPAA at this institution were divided into three groups by date of the IPAA: those operated from 1983 to 1993, from 1994 to 2004 and from 2005 to 2015. Demographics, patient comorbidity, surgical techniques, postoperative outcomes, pouch function and quality of life were analysed. RESULTS: In all, 4525 patients had a primary IPAA. With each decade, increasing numbers of surgeons were involved (decade I, 8; II, 16; III, 31), patients tended to be sicker (higher American Society of Anesthesiologists score) and three-staged pouches became more common. After an initial popularity of the S pouch, J pouches became dominant and a mucosectomy rate of 12% was standard. The laparoscopic technique blossomed in the last decade. 90-day postoperative morbidity by decade was 38.3% vs 50% vs 48% (P < 0.0001), but late morbidity decreased from 74.2% through 67.1% to 30% (P < 0.0001). Functional results improved, but quality of life scores did not. Pouch survival rate at 10 years was maintained (94% vs 95.2% vs 95.2%; P = 0.06). CONCLUSION: IPAA is still evolving. Despite new generations of surgeons, a more accurate diagnosis, appropriate staging and the laparoscopic technique have made IPAA a safer, more effective and enduring operation.

Genetic influences on hormonal markers of chronic hypothalamic-pituitary-adrenal function in human hair.

BACKGROUND: Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function. METHOD: In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80-19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type. RESULTS: Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone. CONCLUSIONS: Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.

Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot.

Undifferentiated fever, or bovine respiratory disease complex (BRDc), is a challenging multi-factorial health issue caused by viral/bacterial pathogens and stressors linked to the transport and mixing of cattle, negatively impacting the cattle feedlot industry. Common practice during processing at feedlots is administration of antibiotic metaphylaxis to reduce the incidence of BRDc. Nitric oxide (NO) is a naturally occurring nano-molecule with a wide range of physiological attributes. This study evaluated the metaphylactic use of intranasal NO releasing spray (NORS) to control BRDc incidence in calves at low-moderate risk of developing BRDc, arriving at a commercial feedlot as compared to conventional antibiotic metaphylaxis. One thousand and eighty crossbred, multiple-sourced, commingled, commercial, weaned beef calves were screened, enrolled, randomized and treated upon arrival. Animals appearing sick were pulled (from their pen) by blinded pen keepers then assessed for BRDc symptoms; blood samples were taken for haptoglobin quantification and the animals were rescued with an antibiotic. After 35 days both groups showed no significant difference in BRDc incidence (5.2% of animals from NORS group and 3.2% from antibiotic group). Average daily weight gain of animals at day 150 for the NORS cohort was 1.17kg compared to 1.18kg for the antibiotic group (p>0.05). There was no significant difference in mortality in the first 35 days (p=0.7552), however, general mortality over 150 days trended higher in the antibiotic cohort. NORS treatment was shown to be safe, causing neither distress nor adverse effects on the animals. This large randomized controlled study in low-moderate BRDc incidence risk calves demonstrates that NORS treatment, as compared to conventional metaphylactic antibiotics, is non-inferior based on BRDc incidence and other metrics like weight and mortality. These data justify further studies in higher BRDc incidence risk populations to evaluate NORS as an alternative strategy to reduce sub-therapeutic metaphylaxis antibiotic use in beef cattle production.

Short-term outcomes of laparoscopic versus open total colectomy with ileorectal anastomosis: a case-matched analysis from a nationwide database.

BACKGROUND: In the current study, we aimed to compare peri- and postoperative 30-day outcomes of patients undergoing laparoscopic versus open total colectomy with ileorectal anastomosis in a case-matched design using data procedure-targeted database. METHODS: Patients who underwent elective total colectomy with ileorectal anastomosis in 2012 and 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into two groups according to the type of surgical approach (laparoscopic and open). Laparoscopic and open groups were matched (1:1) based on age, gender, diagnosis, body mass index, and American Society of Anesthesiologists classification. Comorbidities, perioperative, and short-term (30-day) postoperative outcomes were compared between the matched groups. RESULTS: We identified 1442 patients-549 in the laparoscopic group and 893 patients in the open group. After case matching, there were 326 patients in each group. There were 48 (14.7%) patients who had conversion in the laparoscopic group. The open group had a higher proportion of patients with ascites [0 (0%) vs. 7 (2.1%) p = 0.015], preoperative weight loss [26 (8.0%) vs. 45 (13.8%) p = 0.018], and contaminated wound classifications [Clean/Contaminated 261 (80%) vs. 240 (74%), Contaminated 55 (16.9%) vs. 54 (16.6%), and Dirty/Infected 8 (2.5%) vs. 28 (8.6%), (p = 0.003)]. The laparoscopic group had a significantly longer operative time (242 ± 98 vs. 202 ± 116 min, p < 0.001), shorter hospital stay (9.4 ± 8.5 vs. 13.3 ± 10.7 days, p < 0.001), and lower ileus rate (23.9 vs. 31.0%, p = 0.045) than the open group. After adjusting for covariates, the differences in terms of operative time and hospital stay remained significant [odds ratio (OR): 0.79, confidence interval (CI) 0.74-0.85 and OR 1.36, CI 1.21-1.52, p < 0.001, respectively]. CONCLUSIONS: Laparoscopic approach for total colectomy with ileorectal anastomosis is associated with a shorter hospital stay but longer operative time compared with an open approach.

The Use of Sonographically Guided Botulinum Toxin Type A (Dysport) Injections Into the Tensor Fasciae Latae for the Treatment of Lateral Patellofemoral Overload Syndrome.

BACKGROUND: Pain in the anterior and lateral parts of the knee during exercise is a common clinical problem for which current management strategies are often unsuccessful. PURPOSE: To investigate the effect of an ultrasound-guided botulinum toxin (BT) injection into the tensor fasciae latae (TFL), followed by physical therapy, in patients classified with lateral patellofemoral overload syndrome (LPOS) who failed to respond to conventional treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 45 patients (mean ± SD age, 32.4 ± 8.6 years) who met the inclusion criteria of (1) activity-related anterolateral knee symptoms, (2) symptoms lasting longer than 3 months, (3) a pathological abnormality confirmed by magnetic resonance imaging, and (4) previous failed physical therapy received an ultrasound-guided injection of BT into the TFL followed by physical therapy. Patient-reported outcomes were collected at 5 intervals: before the injection; at 1, 4, and 12 weeks after the injection; and at a mean 5 years after the injection. In 42 patients, relative iliotibial band (ITB) length changes were assessed using the modified Ober test at the first 4 time points. A computational model was run to simulate the effect of TFL weakening on gluteus medius (GMed) activity. Statistical analysis was undertaken using 1-way analysis of variance and paired t tests with Bonferroni post hoc correction. RESULTS: There was a significant improvement in Anterior Knee Pain Scale scores from before the injection (61 ± 15) to 1 (67 ± 15), 4 (70 ± 16), and 12 weeks (76 ± 16) after the injection and in 87% of patients (39/45 patients available for follow-up) at approximately 5 years (from 62.9 ± 15.4 to 87.0 ± 12.5) after the injection (all P < .010). A significant effect on the modified Ober test was identified as a result of the intervention, with an increase in leg drop found at 1 (3° ± 5°), 4 (4° ± 5°), and 12 (7° ± 6°) weeks after the injection compared with before the injection (all P < .010). Simulating a progressive reduction in TFL strength resulted in corresponding increases in GMed activity during gait. CONCLUSION: An injection of BT into the TFL, combined with physical therapy, resulted in a significant improvement of symptoms in patients with LPOS, which was maintained at 5-year follow-up. This may result from reduced lateral TFL/ITB tension or to an increase in GMed activity in response to inhibition of the TFL.

The development of a non-invasive behavioral model of thermal heat stress in laboratory mice (Mus musculus).

BACKGROUND: Many behavioral and physiological studies of laboratory mice employ invasive methods such as radio telemetry to measure key aspects of behavior and physiology. Radio telemetry requires surgical implants, which may impact mouse health and behavior, and thus reduce the reliability of the data collected. NEW METHOD: We developed a method to measure key aspects of thermoregulatory behavior without compromising animal welfare. We examined the thermoregulatory response to heat stress in a custom-built arena that permitted the use of simultaneous and continuous infrared thermography (IRT) and video capture. This allowed us to measure changes in surface body temperature and determine total distance traveled using EthoVision XT animal tracking software. RESULTS: Locomotor activity and surface body temperature differed between heat-stressed mice and mice kept within their thermal comfort zone. The former had an increase in surface body temperature and a decline in locomotor activity, whereas the latter had a stable surface body temperature and showed greater activity levels. METHODS: Surface body temperature and locomotor activity are conventionally quantified by measurements taken at regular intervals, which limit the use and accuracy of the data. We obtained data of high resolution (i.e., recorded continuously) and accuracy that allowed for the examination of key physiological measurements such as energy expenditure and peripheral vasomotor tone. CONCLUSIONS: This novel experimental method for studying thermoregulatory behavior in mice using non-invasive tools has advantages over radio-telemetry and represents an improvement in laboratory animal welfare.

Comparing perineal repairs for rectal prolapse: Delorme versus Altemeier.

PURPOSE: Data comparing surgical outcomes and quality of life (QOL) following perineal repair of rectal prolapse are limited. The aim of our study was to compare the short-term outcome and QOL of two perineal procedures in patients with rectal prolapse. METHODS: All patients with full-thickness rectal prolapse admitted to our institution and undergoing Delorme and Altemeier procedures from 2005 to 2013 were identified using an institutional, IRB-approved rectal prolapse database. Short-term outcomes and QOL were compared. RESULTS: Seventy-five patients (93% female) underwent rectal prolapse surgery: 22 Altemeier and 53 Delorme, mean age 72 ± 15 years. Sixty-six percentage of patients were ASA grade III or IV (Table 1). The median hospital stay was longer in Altemeier's group [4 (1­44) days vs. 3 (0­14) days; p = 0.01]. After a median follow-up of 13 (1­88) months, the rate of recurrent prolapse was 14% (n = 11) [Altemeier 2 (9%) vs. Delorme 9 (16%) p = 0.071]. Postoperative complication rate was 12% (n = 9) [Altemeier 5 (22%) vs. Delorme 4 (7%), p = 0.04]. There was no mortality. The Cleveland Global Quality of Life scores in each group were 0.6 ± 0.2 and 0.5 ± 0.3, respectively (p = 0.59), and were not changed by the surgery. CONCLUSIONS: In patients where abdominal repair of rectal prolapse is judged to be unwise, a Delorme procedure offers short-term control of the prolapse with low risk of complications and with reasonable function. In addition, patients that recur after a Delorme procedure can undergo another similar transanal procedure without compromising the vascular supply of the rectum.

Demonstration of High Performance in Layered Deuterium-Tritium Capsule Implosions in Uranium Hohlraums at the National Ignition Facility.

We report on the first layered deuterium-tritium (DT) capsule implosions indirectly driven by a "high-foot" laser pulse that were fielded in depleted uranium hohlraums at the National Ignition Facility. Recently, high-foot implosions have demonstrated improved resistance to ablation-front Rayleigh-Taylor instability induced mixing of ablator material into the DT hot spot [Hurricane et al., Nature (London) 506, 343 (2014)]. Uranium hohlraums provide a higher albedo and thus an increased drive equivalent to an additional 25 TW laser power at the peak of the drive compared to standard gold hohlraums leading to higher implosion velocity. Additionally, we observe an improved hot-spot shape closer to round which indicates enhanced drive from the waist. In contrast to findings in the National Ignition Campaign, now all of our highest performing experiments have been done in uranium hohlraums and achieved total yields approaching 10^{16} neutrons where more than 50% of the yield was due to additional heating of alpha particles stopping in the DT fuel.

Polymorphisms in a desaturase 2 ortholog associate with cuticular hydrocarbon and male mating success variation in a natural population of Drosophila serrata.

Elucidating the nature of genetic variation underlying both sexually selected traits and the fitness components of sexual selection is essential to understanding the broader consequences of sexual selection as an evolutionary process. To date, there have been relatively few attempts to connect the genetic variance in sexually selected traits with segregating DNA sequence polymorphisms. We set out to address this in a well-characterized sexual selection system--the cuticular hydrocarbons (CHCs) of Drosophila serrata--using an indirect association study design that allowed simultaneous estimation of the genetic variance in CHCs, sexual fitness and single nucleotide polymorphism (SNP) effects in an outbred population. We cloned and sequenced an ortholog of the D. melanogaster desaturase 2 gene, previously shown to affect CHC biosynthesis in D. melanogaster, and associated 36 SNPs with minor allele frequencies > 0.02 with variance in CHCs and sexual fitness. Three SNPs had significant multivariate associations with CHC phenotype (q-value < 0.05). At these loci, minor alleles had multivariate effects on CHCs that were weakly associated with the multivariate direction of sexual selection operating on these traits. Two of these SNPs had pleiotropic associations with male mating success, suggesting these variants may underlie responses to sexual selection due to this locus. There were 15 significant male mating success associations (q-value < 0.1), and interestingly, we detected a nonrandom pattern in the relationship between allele frequency and direction of effect on male mating success. The minor-frequency allele usually reduced male mating success, suggesting a positive association between male mating success and total fitness at this locus.