Responses to thermal and salinity stress in wild and farmed Pacific oysters Crassostrea gigas.

The Pacific oyster Crassostrea gigas was introduced from Japan to many countries in the world for oyster farming, resulting in the establishment of wild populations in intertidal zones and resource competition with local faunas. This study examined physiological responses of wild oysters and farmed oysters to thermal (15°C, 25°C, 37°C and 44°C) and salinity stress (39, 50 and 60ppt). The wild oysters produced more 72kDa heat shock proteins when the temperature increased from 15°C to 25°C and 37°C and the salinity increased from 39 to 50 and 60ppt. However, the amount of 69kDa heat shock protein was similar between farmed and wild oysters when the temperature increased from 15°C to the sublethal temperature 37°C, but it was lower in wild oysters than in farmed oysters when the temperature increased from 15°C to the lethal temperature 44°C. In the tissues, wild oysters used more glycogen to promote metabolic activities by increasing the level of AEC (adenylate energy charge). The results suggest that farmed oysters might have limited ability to cope with heat stress due to low energy reserve and glycolysis activity for HSP synthesis. This study provides experimental evidence on differential responses between wild and farmed oysters to temperature and salinity changes, leading to a better understanding on the pattern of distribution for invading oyster species in the marine environment and the adaptation of marine invertebrates to the threat of climate change.

Thermal tolerance in juvenile King George whiting (Sillaginodes punctata) reduces as fish age and this reduction coincides with migration to deeper colder water.

Heat shock proteins (HSPs) are sensitive and readily produced under thermal stress in many fish species and thus serve as a useful stress bio-indicator. Two experiments were conducted to test the hypothesis that King George whiting (KGW) Sillaginodes punctata approaching sexual maturity exhibits a decrease in HSP production and that exposure to high temperatures provokes HSP production in juvenile whiting. Both adult and juvenile whiting expressed significant increases in HSP69 in response to temperature shocks of 24, 26, 28 and 30 °C. Juvenile whiting had significantly higher HSP69 than adults and expressed more HSP69 at 24 and 26 °C. No mortalities were observed in juvenile fish at 30 °C while 50% of adults suffered mortality at 30 °C. Following exposure of juveniles to 24, 26 and 28 °C, HSP69 was measured at 24, 96 and 168 h. HSP69 peaked at 96 h and returned to the 24h level after 168 h exposure. This study indicates that juveniles can cope with high temperatures better than adults, which offers a partial explanation to fish movement patterns in nature where younger fish inhabit near shore waters and then migrate to deep water towards maturation. Further, this work implies that KGW growth and recruitment can be affected by increasing temperatures due to global warming.

A pocket-sized disposable device for testing the integrity of sensation in the outpatient setting.

AIMS: To compare the Ipswich Touch Test and the VibraTip with the Neuropathy Disability Score and the vibration perception threshold for detecting the 'at-risk' foot. METHODS: We directly compared the Ipswich Touch Test and the VibraTip with both the Neuropathy Disability Score ≥ 6 and the vibration perception threshold ≥ 25 V indicating 'at-risk' feet in 83 individuals. RESULTS: The vibration perception threshold and Neuropathy Disability Score tests exhibited almost perfect agreement with each other (P < 0.001). The VibraTip and Ipswich Touch Test results were identical (P < 0.001). The VibraTip and Ipswich Touch Test results also exhibited almost perfect agreement with the vibration perception threshold (P < 0.001) and the Neuropathy Disability Score (P < 0.001). CONCLUSIONS: These two simple and efficient tests are easy to teach, reliable and can be used in any setting, and neither requires an external power source. We conclude that both the VibraTip and the Ipswich Touch Test are reliable and sensitive tests for identifying the 'high-risk' foot.

Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation in vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding.

Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to adenosine deaminase (ADA). CD26 is costimulatory for lymphocytes and has a circulating soluble form (sCD26). DPP IV enzyme inhibition is a new successful type 2 diabetes therapy. We examined whether the ADA binding and catalytic functions of sCD26 contribute to its effects on T-cell proliferation. Wildtype soluble recombinant human CD26 (srhCD26), an enzyme inactive mutant (srhCD26E-) and an ADA non-binding mutant (srhCD26A-) were co-incubated in in vitro T-cell proliferation assays with peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA), muromonab-CD3 or Herpes simplex virus antigen (HSV Ag). Both srhCD26 and srhCD26E- enhanced PHA-induced T-cell proliferation dose-dependently in all six subjects tested. srhCD26 and srhCD26A- had no overall effect on anti-CD3-stimulated PBMC proliferation in four of five subjects. srhCD26, srhCD26E- and srhCD26A- enhanced HSV Ag induced PBMC proliferation in low responders to HSV Ag, but had no effect or inhibited proliferation in HSV-high responders. Thus, effects of soluble human CD26 on human T-cell proliferation are mechanistically independent of both the enzyme activity and the ADA-binding capability of sCD26.

Dipeptidyl peptidase 4 inhibitors: Applications in innate immunity?

Dipeptidyl peptidase (DPP)-4 inhibitors are a class of orally available, small molecule inhibitors that prolong the insulinotropic activity of the incretin hormone glucagon-like peptide-1 (GLP-1) and are highly effective for the treatment of Type-2 diabetes. DPP4 can also cleave several immunoregulatory peptides including chemokines. Emerging evidence continues to implicate DPP4 inhibitors as immunomodulators, with recent findings suggesting DPP4 inhibitors modify specific aspects of innate immunity. This review summarises recent insights into how DPP4 inhibitors could be implicated in endothelial, neutrophil and monocyte/macrophage mediated immunity. Additionally, this review highlights additional avenues of research with DPP4 inhibitors in the context of the COVID-19 pandemic.

A single beta-globin locus control region element (5' hypersensitive site 2) is sufficient for developmental regulation of human globin genes in transgenic mice.

The beta-globin gene complex is regulated by an upstream locus control region (LCR) which is responsible for high-level, position-independent, erythroid-cell-specific expression of the genes in the cluster. Its role in the developmental regulation of beta-like globin gene transcription remains to be established. We have examined the effect of a single LCR element, hypersensitive site 2 (HS2), on the developmental regulation of the human fetal gamma and adult beta genes in transgenic mice. In mice bearing HS2A gamma beta and HS2G gamma A gamma-117 delta beta human globin gene constructs, switching from gamma- to beta-gene expression begins at about day 13.5 of gestation and is largely completed shortly after birth. The larger construct also demonstrates a switch in G gamma- to A gamma-gene expression during the gamma-to-beta switch similar to that observed during normal human development. We conclude that HS2 alone is sufficient for developmental regulation of the human beta-globin genes.

An analysis of dynamic forces transmitted through the foot in diabetic neuropathy.

OBJECTIVE: Biomechanical studies in diabetic neuropathy have clearly demonstrated abnormal foot pressures, but information on other aspects of gait is limited. This study aimed to investigate and describe the forces transmitted through the foot during walking in diabetic subjects with varying degrees of peripheral neuropathy and to determine if abnormalities in these forces might contribute to the risk of plantar ulceration. RESEARCH DESIGN AND METHODS: Subjects from the following groups were included: healthy control subjects (C); diabetic control subjects (D); subjects with diabetic neuropathy (DN); subjects with previous neuropathic ulceration (DNU); and subjects with Charcot neuro-arthropathy (CH). Gait analysis was performed as subjects walked over a Kistler force plate. Peak forces were measured (as percent body weight) in the vertical and horizontal planes. Comparisons were made between all of the groups and between each diabetic group and a healthy control group matched for walking speed. RESULTS: There were 181 subjects studied. In comparison with that of the speed-matched controls, the mean peak vertical force was higher in each of the diabetic groups, especially in the most neuropathic subjects (DNU, 113 vs. 110%, P < 0.01). This increase was entirely due to higher forces during heel contact (DNU, 111 vs. 106%, P < 0.001). The single peak force occurred during heel strike (rather than during foot push-off) in 23-38% of footsteps of healthy and diabetic control subjects but in 53-73% of footsteps of neuropathic subjects. There was also a trend for higher peak medial forces (CH, 6.2 vs. 5.5%, P < 0.05). CONCLUSIONS: Diabetic neuropathy is associated with a change in the time pattern of the forces transmitted through the foot and an increase in the vertical forces through the heel. The magnitude of the changes is small in absolute terms, but these changes may contribute to the risk of plantar foot ulceration.

Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration.

OBJECTIVE: To investigate longitudinally prognostic factors for foot ulceration in a large population of diabetic patients with established neuropathy. RESEARCH DESIGN AND METHODS: A double-blind multicenter study of a potential new agent for diabetic neuropathy provided the opportunity for this 1-year investigation since intervention demonstrated no efficacy in the condition. A total of 1,035 patients with NIDDM and IDDM were included. Inclusion criteria were vibration perception threshold (VPT) at the great toe > or = 25 V in at least one foot and < or = 50 V in both feet, normal peripheral circulation, and no previous foot ulceration. VPT and clinical components of the Michigan diabetic polyneuropathy (DPN) score were assessed at baseline and subsequent visits. RESULTS: After 1 year, the incidence of first foot ulcers for the total population was 7.2%. Neuropathy parameters were the same between the treatment and placebo groups at baseline and were unchanged at 1 year; therefore, baseline data were combined for multiple regression analysis. VPT, age, and Michigan DPN scores for muscle strength and reflexes were significant independent predictors for first foot ulceration (P < 0.01). For each 1-U increase in VPT values at baseline, the hazard of the first foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength and reflex components of the Michigan DPN scores, the hazard of the first foot ulcer increased by 5.0%. CONCLUSIONS: Tests of VPT and Michigan DPN scores for muscle strength and reflexes are useful clinical predictors for foot ulceration in diabetic patients with established neuropathy. The rate of subsequent ulceration in the following year was alarmingly high, however, despite standardized foot care education at baseline and regular follow-up visits.

A foot care program for diabetic unilateral lower-limb amputees.

OBJECTIVE: To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees. RESEARCH DESIGN AND METHODS: Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of approximately 3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient. RESULTS: For the patients referred to the foot care program, there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle-brachial pressure index was significantly lower for the bilateral amputees (0.75 +/- 0.04) compared with the unilateral amputees (0.90 +/- 0.03, mean +/- SEM, P < 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 +/- 2.16 vs. 31.20 +/- 0.85 mmHg, P < 0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient. CONCLUSIONS: PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies.

Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity.

Dipeptidyl peptidase IV (DPP IV) is a member of the prolyl oligopeptidase family and modifies the biological activities of certain chemokines and neuropeptides by cleaving their N-terminal dipeptides. This paper reports the identification and possible significance of a novel conserved sequence motif Asp-Trp-(Val/Ile/Leu)-Tyr-Glu-Glu-Glu (DW(V/I/L)YEEE) in the predicted beta propeller domain of the DPP IV-like gene family. Single amino acid point mutations in this motif identified two glutamates, at positions 205 and 206, as essential for the enzyme activity of human DPP IV. This observation suggests a novel role in proteolysis for residues of DPP IV distant from the Ser-Asp-His catalytic triad.

Is paraoxonase related to atherosclerosis.

Human serum paraoxonase is responsible for the hydrolysis of organophosphate anticholinesterases, however, whether the enzyme has a physiological role other than the detoxication of insecticides and nerve gases has remained uncertain. Recently, evidence has begun to accumulate of a relationship between the serum activity of paraoxonase and atherosclerosis. Paraoxonase may a fundamental role in lipoprotein metabolism, preventing oxidative changes to low-density lipoprotein which render the particle atherogenic.

Post-proline-cleaving peptidases having DP IV like enzyme activity. Post-proline peptidases.

DP IV has been studied extensively in disease and in the immune system by the use of enzyme assays which detect hydrolysis of Gly-Pro or Ala-Pro substrate. In addition many studies have used inhibitors of DP IV enzyme activity. The characterisation of a novel DP IV like protein, DPP4R, and of other proteases which have a substrate specificity similar to DP IV or that bind DP IV inhibitors suggests that these studies require further evaluation.

Relating structure to function in the beta-propeller domain of dipeptidyl peptidase IV. Point mutations that influence adenosine deaminase binding, antibody binding and enzyme activity.

Point mutations in human CD26/DP IV were analysed for adenosine deaminase (ADA) binding, monoclonal antibody (mAb) binding and DP IV enzyme activity. Point mutations at either Leu294 or Val341 ablated ADA binding. Binding by mAbs that inhibit ADA binding was found to involve both Leu340 to Arg343 and Thr440/Lys441. Glu205 and Glu206 were found to be essential for enzyme activity. All residues of interest were mapped onto a model of the beta-propeller domain of DP IV. These data led us to suggest that in DP IV and related peptidases ligand and antibody binding sites are non-linear and that enzyme activity depends on charged sidechains that surround the entrance to the central tunnel of the beta-propeller.

Intraoperative nursing activities performed by surgical technologists.

In this study of delegated intraoperative nursing activities performed by surgical technologists (STs) in low-risk and high-risk surgical procedures, 343 OR directors, perioperative nurses, and STs from rural, community, and medical center hospitals reported that STs frequently perform activities related to surgical counts, the sterile field, and equipment and supplies. Surgical technologists do not frequently perform tasks related to patient transportation, teaching, medication administration, OR environment, patient monitoring, and patients' rights. The investigator used nine competency statements of intraoperative nursing as a framework for the research instrument. Data analysis determined that the levels of risk in patient situations affects how frequently STs perform transportation, teaching, sterile field, OR environment, and patients' rights activities.

The impaired nurse. Part II: Management strategies.

The perioperative nurse manager faces an ethical dilemma when faced with an impaired colleague. An effort to support impaired practitioners and to ensure patient safety and quality of care seem incompatible. To facilitate both, violations of the state nurse practice act must be reported, and the employee terminated if your documentation is adequate and treatment options you offer are not pursued. This harsh approach is necessary when the impaired practitioner puts patient care at risk. Kindness promotes chemical dependency, and the harsh action may be the only event that breaks through the denial. Fifteen percent of impaired practitioners who receive coordinated, supportive, and confrontational management are not motivated to seek treatment. Nurses must remember, however, that the remaining 85% respond positively to an established and comprehensive chemical dependency policy. Defined decision-making strategies concerning chemical dependency at the state and local level motivate practitioners to seek treatment to avoid licensure action. Perioperative nurses must meet the challenge to effectively manage chemical dependency. Employing recovering nurses in a structured framework is creative resource management. The ability to conserve talented and skilled practitioners preserves the nurturing strength of nurses and increases professional cohesion.

Delegating intraoperative activities. A pilot study.

The purpose of phase one of this descriptive study was to obtain information about the research process. We identified problems associated with the pilot and examined the feasibility of completing phase two of the study at the national level. The pilot provided insight into the weaknesses and strengths of the tool design. It also identified interesting trends and data regarding delivery of intraoperative nursing care. The pilot study supported the ultimate goals of the research project, and we plan to continue with phase two of the study. Further research is needed to substantiate the findings and solidify the implications for perioperative nursing.