Using IPM-CPR as a Management Program for Apple Orchards.

We have demonstrated how management of key orchard pests including the insect invasive species Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) can be accomplished using a systems-level approach termed IPM-CPR (Integrated Pest Management-Crop Perimeter Restructuring) in apple. We conducted on-farm comparisons of IPM-CPR to standard management program for managing H. halys, Cydia pomonella (L.) (Lepidoptera: Tortricidae), Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae) in commercial apple orchards in 2014, 2016, and 2017 in New Jersey, Maryland, and Virginia. The presence and abundance of key pests and fruit injury at harvest were used as a measure of success of the program. We compared the amount of insecticide applied for each management program. In majority of instances, there were no differences in the IPM-CPR and the standard management program in terms of H. halys numbers in baited pyramid traps and stink bug injury at harvest. Damage from C. pomonella and G. molesta in the IPM-CPR treatment was significantly lower than the standard management program in 2014 and 2017. Amount of active ingredient used was on average 62.1% lower in the IPM-CPR treatment compared with standard management program. Despite a reduction in insecticide use, there were minimal impacts on beneficial insects. Overall, IPM-CPR in apples successfully managed key orchard pests, including H. halys, and used significantly less insecticide than a standard insecticide-based management program and could be adopted as a systems-level approach for pest population reduction.

Exercise-induced alterations and loss of sarcomeric M-line organization in the diaphragm muscle of obscurin knockout mice.

We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution of ankyrin B (ankB), disorganization of the subsarcolemmal microtubules, and reduced localization of dystrophin at costameres. In addition, these mice have impaired running endurance and increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach of physiological, morphological, and structural studies in which we further characterize the skeletal muscles of obscurin KO mice. A detailed examination of exercise performance, using different running protocols, revealed that the reduced endurance of obscurin KO animals on the treadmill depends on exercise intensity and age. Indeed, a mild running protocol did not evidence significant differences between control and obscurin KO mice, whereas comparison of running abilities of 2-, 6-, and 11-mo-old mice exercised at exhaustion revealed a progressive age-dependent reduction of the exercise tolerance in KO mice. Histological analysis indicated that heavy exercise induced leukocyte infiltration, fibrotic connective tissue deposition, and hypercontractures in the diaphragm of KO mice. On the same line, electron microscopy revealed that, in the diaphragm of exercised obscurin KO mice, but not in the hindlimb muscles, both M-line and H-zone of sarcomeres appeared wavy and less defined. Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.

Deletion of small ankyrin 1 (sAnk1) isoforms results in structural and functional alterations in aging skeletal muscle fibers.

Muscle-specific ankyrins 1 (sAnk1) are a group of small ankyrin 1 isoforms, of which sAnk1.5 is the most abundant. sAnk1 are localized in the sarcoplasmic reticulum (SR) membrane from where they interact with obscurin, a myofibrillar protein. This interaction appears to contribute to stabilize the SR close to the myofibrils. Here we report the structural and functional characterization of skeletal muscles from sAnk1 knockout mice (KO). Deletion of sAnk1 did not change the expression and localization of SR proteins in 4- to 6-mo-old sAnk1 KO mice. Structurally, the main modification observed in skeletal muscles of adult sAnk1 KO mice (4-6 mo of age) was the reduction of SR volume at the sarcomere A band level. With increasing age (at 12-15 mo of age) extensor digitorum longus (EDL) skeletal muscles of sAnk1 KO mice develop prematurely large tubular aggregates, whereas diaphragm undergoes significant structural damage. Parallel functional studies revealed specific changes in the contractile performance of muscles from sAnk1 KO mice and a reduced exercise tolerance in an endurance test on treadmill compared with control mice. Moreover, reduced Qγ charge and L-type Ca(2+) current, which are indexes of affected excitation-contraction coupling, were observed in diaphragm fibers from 12- to 15-mo-old mice, but not in other skeletal muscles from sAnk1 KO mice. Altogether, these findings show that the ablation of sAnk1, by altering the organization of the SR, renders skeletal muscles susceptible to undergo structural and functional alterations more evident with age, and point to an important contribution of sAnk1 to the maintenance of the longitudinal SR architecture.

Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway.

During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway. Our findings suggest that during ageing there is no downregulation of IGF1/Akt pathway and that sarcopenia is not due to FoxO activation and upregulation of the proteolytic systems. A potentially interesting result was the increased phosphorylation of the ribosomal protein S6, indicative of increased activation of mTOR complex1 (mTORC1), in aged mice. This result may provide the rationale why rapamycin treatment and caloric restriction promote longevity, since both interventions blunt activation of mTORC1; however, this change was not statistically significant in humans. Finally, genetic perturbation of these pathways in old mice aimed at promoting muscle hypertrophy via Akt overexpression or preventing muscle loss through inactivation of the ubiquitin ligase atrogin1 were found to paradoxically cause muscle pathology and reduce lifespan, suggesting that drastic activation of the IGF1-Akt pathway may be counterproductive, and that sarcopenia is accelerated, not delayed, when protein degradation pathways are impaired.

Role of satellite cells in muscle growth and maintenance of muscle mass.

Changes in muscle mass may result from changes in protein turnover, reflecting the balance between protein synthesis and protein degradation, and changes in cell turnover, reflecting the balance between myonuclear accretion and myonuclear loss. Myonuclear accretion, i.e. increase in the number of myonuclei within the muscle fibers, takes place via proliferation and fusion of satellite cells, myogenic stem cells associated to skeletal muscle fibers and involved in muscle regeneration. In developing muscle, satellite cells undergo extensive proliferation and most of them fuse with myofibers, thus contributing to the increase in myonuclei during early postnatal stages. A similar process is induced in adult skeletal muscle by functional overload and exercise. In contrast, satellite cells and myonuclei may undergo apoptosis during muscle atrophy, although it is debated whether myonuclear loss occurs in atrophying muscle. An increase in myofiber size can also occur by changes in protein turnover without satellite cell activation, e.g. in late phases of postnatal development or in some models of muscle hypertrophy. The relative role of protein turnover and cell turnover in muscle adaptation and in the establishment of functional muscle hypertrophy remains to be established. The identification of the signaling pathways mediating satellite cell activation may provide therapeutic targets for combating muscle wasting in a variety of pathological conditions, including cancer cachexia, renal and cardiac failure, neuromuscular diseases, as well as aging sarcopenia.

Follow-up on the treatment of panic disorder with or without agoraphobia: a quantitative review.

We conducted a meta-analysis to update the knowledge of long-term efficacy of different treatments in panic disorder with or without agoraphobia. Included were 68 studies pertaining to 106 treatment conditions and 1346 patients. Effect sizes Cohen's d were calculated within the treatment conditions at posttest and at follow-up for panic and agoraphobia. A comparison was made between six treatments: high-potency benzodiazepines, antidepressants, psychological panic management, exposure in vivo, antidepressants combined with exposure, and psychological panic management combined with exposure in vivo. The mean (+/- SD) duration of the follow-up period was 62 +/- 89 weeks. In the majority of the studies (84%), follow-up had a naturalistic character. The lack of information about treatments received between posttest and follow-up limits the interpretation of the results. For all conditions, the treatment gains at posttest were maintained during the follow-up period. The mean (+/- SD) d for panic was 1.11 +/- 0.70 at posttest and 1.28 +/- 0.61 at follow-up; for agoraphobia, the mean d at posttest was 1.36 +/- 1.10 and at follow-up it was 1.41 +/- 0.82. Significant differences were found in efficacy on agoraphobic measures at follow-up between the combination of antidepressants and exposure in vivo versus psychological panic management, exposure in vivo, and the combination of psychological panic management and exposure. Overall, the data suggest that different treatment options for panic disorder with or without agoraphobia are effective at both posttest and follow-up. Research on long-term treatment, discontinuation of therapies, and interventions between posttest and follow-up need more attention, for pharmacotherapy as well as psychotherapy.

A meta-analysis of the treatment of panic disorder with or without agoraphobia: a comparison of psychopharmacological, cognitive-behavioral, and combination treatments.

To compare short-term efficacy of benzodiazepines, antidepressants, psychological panic management, exposure in vivo, and combination treatments in panic disorder with or without agoraphobia (PA), a meta-analysis was conducted. Included were 106 studies, pertaining to 222 treatment conditions, 5,011 patients at pretest and 4,016 at posttest. Pre/post effect sizes Cohen's d were calculated within the treatment conditions for four clinical variables: panic, agoraphobia, depression, and general anxiety. Seven large treatment conditions were used in the main analyses: high-potency benzodiazepines, antidepressants, psychological panic management, exposure in vivo, pill-placebo combined with exposure, antidepressants combined with exposure, and psychological panic management combined with exposure in vivo. First, these treatments were compared with a control condition, consisting of pill-placebo, attention placebo, and waiting list. Next, a comparison was made between the treatments. Antidepressants, psychological panic management, high-potency benzodiazepines, and antidepressants combined with exposure in vivo were superior to the control condition for panic attacks. Exposure in vivo alone was not effective for panic attacks. With regard to agoraphobic avoidance, all seven treatments were superior to the control condition. When comparing the various treatment conditions, no differences concerning panic attacks were found. For agoraphobic avoidance, the combination of antidepressants with exposure in vivo was superior to the other conditions. The combination of antidepressants with exposure in vivo is the most potent short-term treatment of PA.

Bacterial translocation in D-galactosamine-treated rats in a burn model.

Bacteria and endotoxins can pass through the gut barrier under certain conditions. This process of bacterial translocation (BT) may occur after thermal injury in animals and is thought to play a role in the pathogenesis of septic complications in severely burned patients. The current study was performed to determine the role of endotoxin-related cytokines in the pathogenesis of burn-induced BT. Wistar rats were used in which enhanced sensitivity to TNF/LPS reactions was achieved by treatment with galactosamine (GalN). The GI tracts of these rats were antibiotic decontaminated with oral bacitracin and neomycin and were colonized with a neomycin resistant (NR)-Escherichia coli strain. The rats were divided into four groups, 30 per cent TBSA scald with GalN (Burn+GalN) pretreatment; 30 per cent TBSA scald without GalN (Burn); or sham injury with (GalN) and without GalN (Sham) pretreatment. On day 2, the animals were killed and liver, spleen, lung, heart and the peritoneal cavity were cultured. Blood samples were taken and the concentrations of LPS, TNF, IL-6 and ALAT were determined. Mortality was significantly increased in the Burn+GalN group compared to the other groups. In all groups, the incidences of BT were increased compared to the sham-treated group, although BT was most pronounced in the Burn+GalN group. In the latter group it was accompanied by highly elevated IL-6 and ALAT levels. The results of this study suggest that endotoxin mediators like TNF and IL-6 could play a role in the phenomenon of BT and that the function of the liver is an important clearing mechanism.

Dextran-magnetite particles: contrast-enhanced MRI of blood-brain barrier disruption in a rat model.

Dextran-magnetite particles (DMP) were studied for their use as a MR contrast agent to visualize lesions with a blood-brain barrier (bbb) disruption. A freezing injury to the rat cerebral cortex was used as a model of bbb disruption. The biodistribution of iv-injected DMP was studied using atomic absorption spectrophotometry, electron microscopy, and MRI. One hour after injection, focal accumulation of the particles in capillary endothelial cells could be demonstrated in the freezing lesion. Despite the observation that the relaxivity of DMP in vivo appears to be less well pronounced than that in vitro, the MR imaging studies show that DMP can be used to visualize bbb disruption with adequate contrast.

Major abdominal operations in acquired immunodeficiency syndrome.

Twenty-one major abdominal operations performed on 20 patients with Acquired Immunodeficiency Syndrome (AIDS) were reviewed. Fourteen operations were for therapeutic indications, eight were emergent. The array of pathology encountered included opportunistic infection with Mycobacterium avium intracellulare, Cytomegalovirus, Cryptosporidium, abdominal tuberculosis, lymphoma, Kaposi's sarcoma, AIDS-related immune thrombocytopenia, perforated appendicitis and colonic pseudo-obstruction. Hospital mortality was 20 per cent. Major morbidity occurred in 15 per cent of patients and was more common following emergency operations. Preoperative demographic, hematologic, or nutritional parameters examined or the presence of single-organ system dysfunction did not predict outcome. Fifty-three per cent of hospital survivors are alive with a nine-month median postoperative follow-up. It is concluded that major abdominal procedures in patients with AIDS should not be withheld due to fear of excessive morbidity or mortality. General surgeons are involved in the evaluation and treatment of increasing numbers of patients with HIV infection. Appropriate management requires recognition of a wide range of surgical pathology and attention to details of safe intraoperative conduct.

Passage of DMP across a disrupted BBB in the context of antibody-mediated MR imaging of brain metastases.

To study the possible application of monoclonal antibody/dextran-magnetite conjugates in specific MR imaging of brain metastases, both components of these conjugates were tested for their ability to penetrate the endothelium during conditions of local blood-brain barrier (BBB) impairment. The passage of dextran-magnetite particles (DMP) across a disrupted blood-brain barrier was studied in a freezing lesion model using electron microscopy (EM) and MR imaging. One hour after i.v. injection, focal accumulation of DMP in capillary endothelial cells within the freezing lesion was shown by EM. In parallel with this, MR imaging indicated a strong contrast enhancement in the lesion. EM observations showed that the particles were still present in the endothelial cells four and eight hours after injection. The passage of an anti-small cell lung cancer (SCLC) monoclonal antibody across the endothelium of intracerebrally xenografted human SCLC was studied using immunohistological techniques. It was found that passage across endothelial cell occurred in the tumor within four hours after injection.

Monocyte functional studies in asymptomatic, human immunodeficiency disease virus (HIV)-infected individuals.

Various aspects of monocyte-associated function were evaluated in the peripheral blood mononuclear cells of male homosexuals who were infected with the human immunodeficiency disease virus (HIV). The functional assessments included indomethacin-sensitive regulation of blastogenesis and lymphokine-activated killer (LAK)-cell induction, chemiluminescent responses of mononuclear leukocytes to opsonized zymosan, and the expression of HLA-DR antigen on CD-14-positive monocytes. The results obtained demonstrate that each of these functions is abnormal in asymptomatic individuals who have HIV core antigen (p24) in their circulation. These results suggest that monocyte abnormalities which could contribute to immune dysfunction in HIV-infected patients can be detected early during the course of HIV infection and are associated with the expression of serum HIV antigen.

Diagnosis of human immunodeficiency virus infection in seronegative homosexuals presenting with an acute viral syndrome.

Early diagnosis of acute human immunodeficiency virus (HIV) infection is difficult because patients may be seronegative for HIV at the time of presentation. We have used a serum HIV antigen (HIV-Ag) enzyme immunoassay (EIA) to diagnose acute HIV infection in four high-risk patients. The clinical syndrome in these four patients was characterized by fever (four), rash (three), myalgias-arthralgias (three), and pharyngitis (two). All patients had spontaneous resolution of their symptoms within eight to 12 days. Serum HIV antibody, as measured by a commercially available screening EIA and by Western blot analysis, was negative in all patients at time of presentation and all seroconverted on subsequent testing. Human immunodeficiency virus was isolated from two of two patients during the acute illness. Initial serum samples from all four patients were positive for HIV-Ag. Serum samples of three of four patients became negative for HIV-Ag and positive for HIV antibody. These data suggest that serum HIV-Ag detection by EIA may be useful in the diagnosis of the acute syndrome caused by HIV infection.

Correlation of serum HIV antigen and antibody with clinical status in HIV-infected patients.

An enzyme immunoassay (EIA) has been developed which detects antigen(s) (Ag) of the human immunodeficiency virus (HIV) in the serum of patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and patients at high risk for HIV infection. The test has a sensitivity of approximately 50 pg/ml of HIV protein. The specificity of the assay was determined with various virus infected cell lines, normal human sera/plasma, and serum from patients not known to be at risk for HIV infection. No false-positive HIV-Ag results were seen. Sera from 69% of patients with AIDS were positive for HIV-Ag as were 46% of patients with ARC and 19% of asymptomatic, HIV-antibody-positive individuals. There were significant associations between the stage of HIV infection--ie, AIDS vs ARC vs asymptomatic--and the detection of HIV-Ag in serum (p less than 0.0001) and the lack of detection of antibody to HIV core Ag (p less than 0.0001). HIV-Ag was also found in the serum of two asymptomatic antibody-negative individuals who were at high risk for AIDS and who later developed HIV antibody. The presence of HIV-Ag in sera was confirmed by an inhibition procedure. Thus, HIV-Ag can be detected in the serum of infected individuals prior to antibody production and correlates with the clinical stage of HIV infection.

Sensitivity and specificity of an HIV antibody assay.

We have evaluated a new enzyme immunoassay (EIA) to measure IgG antibodies (Abs) to HIV in patients with AIDS, AIDS-related complex (ARC), AIDS contacts (AC), and low risk controls. Twenty-nine (94%) of 31 AIDS, 27 (96%) of 26 ARC, 12 (54%) of 22 AC, and 1 (2%) of 60 control patients were anti-HIV Ab positive by this assay. Positive results were confirmed by Western blot analysis. The EIA for anti-HIV evaluated in this study is sensitive and specific in identifying individuals who have been infected by this retrovirus.