Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer.

Tissue-resident memory T (TRM ) cells are CD8+ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in TRM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in TRM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate TRM cell phenotypes. We discovered that tumour TRM cells have low DNA methylation in the PRF1 locus (32·9% methylation), which corresponds to increased numbers of perforin-expressing TRM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour TRM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that TRM cells from tumours are not terminally exhausted. Moreover, a high number of TRM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, TRM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies TRM cells as potential new targets for cancer immunotherapy.

Bacterial clearance of biologic grafts used in hernia repair: an experimental study.

BACKGROUND: Biologic grafts used in ventral hernia repair are derived from various sources and undergo different post-tissue-harvesting processing, handling, and sterilization techniques. It is unclear how these various characteristics impact graft response in the setting of contamination. We evaluated four materials in an infected hernia repair animal model using fluorescence imaging and quantitative culture studies. METHODS: One hundred seven rats underwent creation of a chronic hernia. They were then repaired with one synthetic polyester control material (n = 12) and four different biologic grafts (n = 24 per material). Biologic grafts evaluated included Surgisis (porcine small intestinal submucosa), Permacol (crosslinked porcine dermis), Xenmatrix (noncrosslinked porcine dermis), and Strattice (noncrosslinked porcine dermis). Half of the repairs in each group were inoculated with Staphylococcus aureus at 10(4) CFU/ml and survived for 30 days without systemic antibiotics. Animals then underwent fluorescence imaging and quantitative bacterial studies. RESULTS: All clean repairs remained sterile. Rates of bacterial clearance were as follows: polyester synthetic 0%, Surgisis 58%, Permacol 67%, Xenmatrix 75%, and Strattice 92% (P=0.003). Quantitative bacterial counts had a similar trend in bacterial clearance: polyester synthetic 1×10(6) CFU/g, Surgisis 4.3×10(5) CFU/g, Permacol 1.7×10(3) CFU/g, Xenmatrix 46 CFU/g, and Strattice 31 CFU/g (P=0.001). Fluorescence imaging was unable to detect low bacterial fluorescence counts observed on bacterial studies. CONCLUSION: Biologic grafts, in comparison to synthetic material, are able to clear a Staphylococcus aureus contamination; however, they are able to do so at different rates. Bacterial clearance correlated to the level of residual bacterial burden observed in our study. Post-tissue-harvesting processing, handling, and sterilization techniques may contribute to this observed difference in ability to clear bacteria.

Retinoic acid and calcitriol inhibition of growth and NADH oxidase of normal and immortalized human keratinocytes.

Plasma membranes were isolated by aqueous two-phase partition from normal human keratinocytes (HKc) and from human keratinocytes immortalized with human papillomavirus type 16 DNA (HKc/HPV16). The NADH oxidase of plasma membrane vesicles of normal HKc was stimulated by epidermal growth factor whereas that of HKc/HPV16 was not. The NADH oxidase of the plasma membranes from both normal HKc and HKc/HPV16 was inhibited by calcitriol (1 alpha-1,25-dihydroxy vitamin D-3) and retinoic acid. However, with plasma membranes from HKc/HPV16 the NADH oxidase was more susceptible to inhibition by retinoic acid than were membranes from normal HKc. Similarly, clonal growth of HKc/HPV16 was inhibited by retinoic acid at lower concentrations than normal HKc whereas inhibition of clonal growth of normal HKc and HKc/HPV16 by calcitriol showed similar dose-dependencies. Comparing normal HKc and HKc/HPV16, the results demonstrate parallel inhibition of clonal growth and NADH oxidase by both retinoic acid and calcitriol of HKc/HPV16 but not of normal HKc. These results suggest that an increased sensitivity of the plasma membrane NADH oxidase of HKc/HPV16 to retinoic acid may be related to the increased sensitivity of these cells to growth control by retinoic acid. In addition, since plasma membrane NADH oxidase of HKc/HPV16 shows altered responsiveness to growth modulators such as EGF, retinoic acid and calcitriol, it appears that HKc/HPV16 express an NADH oxidase with different characteristics than those of normal HKc.

Revascularization of popliteal and below-knee arteries with polytetrafluoroethylene.

The expanded polytetrafluoroethylene (PTFE) graft (Gore-tex) is the most frequently used synthetic graft when an alternative to autologous saphenous vein is required. Early results have been encouraging. In the present paper we report on 6 years of results from 153 above-knee (AK) femoropopliteal bypass grafts, 74 below-knee (BK) femoropopliteal bypass grafts, and 54 femorotibial/peroneal bypass grafts. The main indication for the vascular reconstruction was severe ischemia. Preventive antibiotics were given to 95% of the patients. Minimum observation time was 1 year after implantation. There was no operative death. Graft infection was seen in less than 5% of patients. The 6-year cumulative limb salvage rate was 87% for patients with severe ischemia in the AK femoropopliteal bypass group, 59% for those in the BK femoropopliteal bypass group, and 57% for those in the femorotibial/peroneal bypass group. The graft patency rate was 88% at 2 years and 78% at 6 years for the AK femoropopliteal bypass group, for whom the operative indication was disabling claudication, and 81% and 68%, respectively, when the indication for the vascular procedure was severe ischemia. The cumulative graft patency rate was 53% and 43% at 2 and 6 years, respectively, after implantation of BK femoropopliteal bypass grafts and 43% and 39% for femorotibial/peroneal bypass procedures. The expanded PTFE (Gore-tex) graft seems therefore to be a good alternative when an autologous vein is not available, even for reconstructions well below the knee joint.

Axillofemoral bypass reconstructions in sixty-one patients with leg ischemia.

During a 5-year period, 61 axillofemoral bypass operations have been performed in patients regarding as poor risks for conventional bifurcations procedures with arteriosclerotic occlusive disease and in patients with graft infections. Velour-Dacron grafts and expanded polytetrafluoroethylene (PTFE)-grafts have been used. The results are encouraging with a 3 year graft patency rate of 75% and a 3 year limb salvage rate of 90%. The expanded PTFE graft is a suitable graft for this purpose, and the use of axillofemoral bypass grafting is recommended as an alternative to the conventional aortoiliac/femoral bypass graft when dealing with high risk patients and patients with graft infections.

The prevalence and predictability of depression in infertile women.

OBJECTIVE: To determine the prevalence, severity, and predictability of depression in infertile women compared with a control sample of healthy women. DESIGN: Subjects were assessed while waiting to see their physician: infertility patients before a visit with an infertility specialist and control subjects before seeing either a gynecologist or internist for a routine gynecological examination. Subjects completed a demographic form and two depression scales. SETTING: A group infertility practice affiliated with an academic medical center, a hospital-based gynecology practice, and a health maintenance organization internal medicine clinic. PARTICIPANTS: 338 infertile women and 39 healthy women. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The Beck Depression Inventory and the Center for Epidemiological Studies Depression Scale. RESULTS: The infertile women had significantly higher depression scores and twice the prevalence of depression than the controls; women with a 2- to 3-year history of infertility had significantly higher depression scores compared with women with infertility durations of < 1 year or > 6 years; women with an identified causative factor for their infertility had significantly higher depression scores than women with unexplained or undiagnosed infertility. CONCLUSIONS: Depressive symptoms are common in infertile women. Psychological interventions aimed at reducing depressive symptoms need to be implemented, especially for women with a definitive diagnosis and for those with durations of 2 to 3 years of infertility.

Herniography in athletes with groin pain.

In the years 1974 to 1981, herniography was performed in 78 athletes with groin pain. The investigation comprised 101 painful groin sides in 23 athletes with bilateral symptoms. Before herniography, a hernia was palpated in only eight (7.9 percent) groins with pain. Hernias were found at herniography in 84.2 percent of the symptomatic groin sides and in 49.1 percent of the asymptomatic groin sides. Sixty-three hernia operations were performed. The herniographic and operative diagnoses corresponded well. Direct hernias dominated among the operated athletes, and were found in 55.6 percent of those below 30 years of age. Altogether 69.8 percent of the operated patients were cured by hernia repair and another 20.6 percent were improved. Tenoperiostitis of the adductor muscles was the most frequent diagnosis in those not cured by operation and among the nonoperated patients. Herniography was of great value in selecting those patients who needed a repair. A broad differential diagnostic approach when examining these patients is of the utmost importance.

Herniography.

With some experience with the technique, herniography is easy to perform and involves very little inconvenience to the patient. This direct method for exact evaluation of the lower part of the abdominal wall and pelvic floor is useful and valuable for this common group of patients with symptoms in the groin or pelvis.

Ligation of the hernial sac?

In a prospective randomized study, the need for a high ligature of the hernial sac at operation for indirect hernia was studied. Herniectomy without ligation of the sac did not increase the recurrence rate. In addition, the nonligated patients had less pain in the postoperative period. Herniography was used pre- and postoperatively to improve the diagnostics.

Ironic effects of trying to relax under stress.

Two studies found that intentional relaxation under conditions of mental load or stress produces ironic increases in skin conductance level (SCL). In Experiment 1, participants instructed to relax under the high mental load of rehearsing a long number had higher SCL than those instructed to relax under low load, and tended to have higher SCL than those under high load not instructed to relax. In Experiment 2, participants were instructed to relax or were not so instructed while they answered questions described either as measures of IQ or as unimportant. Those in the more loading and stressful situation who were asked to relax had greater SCL during the questions than those not asked to relax.

Immediate and long-term outcomes after lateral pancreaticojejunostomy for chronic pancreatitis.

Lateral pancreaticojejunostomy (LPJ) is the recommended surgical treatment of intractable pain from chronic pancreatitis (CP) with obstruction and ductal dilatation. This study evaluated the etiology, morbidity, mortality, hospital costs, and quality of life (QL) for patients with LPJ for CP. Medical records of 60 patients undergoing LPJ for CP between 1988 and 1996 were reviewed. Long-term QL was assessed by the Short Form 36 Health Survey and analyzed against control populations of patients who underwent pancreatic debridement for necrosis and patients with laparoscopic cholecystectomy for cholelithiasis. CP etiologies included 52 per cent alcoholic, 28 per cent idiopathic, 13 per cent pancreatic divisum, and 7 per cent familial pancreatitis. Peri- and postoperative morbidity and mortality were 25 and 0 per cent respectively. Average hospital cost was $13,530 with mean postoperative hospital stay of 12.1 days. Overall physical and mental QL were diminished compared with both the debridement group and cholecystectomy group with particular detriments in areas of physical role (P < 0.05), bodily pain (P < 0.001), social function (P < 0.001), and mental health (P < 0.001). We conclude that LPJ for CP is a relatively safe procedure with low morbidity and mortality but results in a significantly diminished long-term QL relative to other surgical patients with pancreatic or biliary disease. This difference prevails in both physical and mental aspects of health.

Simplest tasks have greatest dual task interference with balance in brain injured adults.

Attention difficulties and poor balance are both common sequel following a brain injury. This study aimed to determine whether brain injured adults had greater difficulty than controls in performing a basic balance task while concurrently completing several different cognitive tasks varying in visuo-spatial attentional load and complexity. Twenty brain injured adults and 20 age-, sex- and education level-matched controls performed a balance-only task (step stance held for 30 s), five cognitive-only tasks (simple and complex non-spatial, visuo-spatial, and a control articulation task), and both together (dual tasks). Brain injured adults showed a greater centre of pressure (COP) excursion and velocity in all conditions than controls. Brain injured adults also demonstrated greater interference with balance when concurrently performing two cognitive tasks than control subjects. These were the control articulation and the simple non-spatial task. It is likely that distractibility during these simple tasks contributed to an increase in COP motion and interference with postural stability in stance. Performing visuo-spatial tasks concurrently with the balance task did not result in any change in COP motion. Dual task interference in this group is thus unlikely to be due to structural interference. Similarly, as the more complex tasks did not uniformly result in increased interference, a reduction in attentional capacity in the brain injured population is unlikely to be the primary cause of dual task interference in this group.

The late results after axillo-femoral bypass grafts in patients with leg ischaemia.

The late results--up to six years--after axillo-femoral bypass reconstruction are reported for 85 patients with leg ischaemia who were regarded as poor-risk patients for aortic bypass surgery, or who had aortic graft infection. Velour-Dacron grafts and expanded polytetrafluoroethylene (PTFE, Gore-Tex)--grafts have been used. The cumulative patency rate (life table) six years after graft implantation was 64% (PTFE-grafts) and 58% (Velour-Dacron grafts). The corresponding cumulative limb salvage rate six years after graft implantation was 88% when PTFE grafts were used and 77% when Velour-Dacron grafts were used. Our results demonstrate that axillo-femoral reconstruction is a useful procedure with a good patency rate 6 years after implantation. This procedure should be considered when dealing with poor risk patients with severe leg ischaemia.

Permanent genetic resources added to Molecular Ecology Resources Database 1 August 2011-30 September 2011.

This article documents the addition of 299 microsatellite marker loci and nine pairs of single-nucleotide polymorphism (SNP) EPIC primers to the Molecular Ecology Resources (MER) Database. Loci were developed for the following species: Alosa pseudoharengus, Alosa aestivalis, Aphis spiraecola, Argopecten purpuratus, Coreoleuciscus splendidus, Garra gotyla, Hippodamia convergens, Linnaea borealis, Menippe mercenaria, Menippe adina, Parus major, Pinus densiflora, Portunus trituberculatus, Procontarinia mangiferae, Rhynchophorus ferrugineus, Schizothorax richardsonii, Scophthalmus rhombus, Tetraponera aethiops, Thaumetopoea pityocampa, Tuta absoluta and Ugni molinae. These loci were cross-tested on the following species: Barilius bendelisis, Chiromantes haematocheir, Eriocheir sinensis, Eucalyptus camaldulensis, Eucalyptus cladocalix, Eucalyptus globulus, Garra litaninsis vishwanath, Garra para lissorhynchus, Guindilla trinervis, Hemigrapsus sanguineus, Luma chequen. Guayaba, Myrceugenia colchagüensis, Myrceugenia correifolia, Myrceugenia exsucca, Parasesarma plicatum, Parus major, Portunus pelagicus, Psidium guayaba, Schizothorax richardsonii, Scophthalmus maximus, Tetraponera latifrons, Thaumetopoea bonjeani, Thaumetopoea ispartensis, Thaumetopoea libanotica, Thaumetopoea pinivora, Thaumetopoea pityocampa ena clade, Thaumetopoea solitaria, Thaumetopoea wilkinsoni and Tor putitora. This article also documents the addition of nine EPIC primer pairs for Euphaea decorata, Euphaea formosa, Euphaea ornata and Euphaea yayeyamana.