Cardiopulmonary Exercise Performance in the Pediatric and Young Adult Population Before and During the COVID-19 Pandemic.

Physical activity (PA) decreased and sedentary behavior (SB) increased in the pediatric population during the Coronavirus Disease 2019 (COVID-19) pandemic. We examined the effects of PA and SB on cardiopulmonary exercise performance in children, adolescents and young adults both with and without underling cardiac disease, and hypothesized that there will be a change in aerobic and physical working capacity during the pandemic. This was a single-center retrospective longitudinal cohort study in patients age 6-22 years who underwent serial maximal cardiopulmonary exercise stress testing before and during the COVID-19 pandemic. Metabolic variables were obtained; PA and SB data were extracted from clinic notes. A total of 122 patients (60% male) underwent serial exercise testing with a median age of 14 years at the first CPET. Predicted peak aerobic capacity significantly decreased among both females and males during the pandemic, even after adjusting for changes in somatic growth. There was no significant change in physical working capacity during the pandemic. Patients who were more aerobically fit experienced a greater decrease in aerobic capacity during the pandemic compared to those less fit. In conclusion, cardiopulmonary exercise performance, notably aerobic activity, decreased during the COVID-19 pandemic in children, adolescents and young adults compared to pre-pandemic values. This decline was most notable in those with the highest pre-pandemic aerobic capacity values and was independent of somatic growth or changes in BMI. This study has public health implications and demonstrates the importance of PA on overall cardiovascular health.

The influence of mechanical Circulatory support on post-transplant outcomes in pediatric patients: A multicenter study from the International Society for Heart and Lung Transplantation (ISHLT) Registry.

BACKGROUND: Mechanical circulatory support (MCS) is increasingly being used as a bridge to transplant in pediatric patients. We compare outcomes in pediatric patients bridged to transplant with MCS from an international cohort. METHODS: This retrospective cohort study of heart-transplant patients reported to the International Society for Heart and Lung Transplantation (ISHLT) registry from 2005-2017 includes 5,095 patients <18 years. Pretransplant MCS exposure and anatomic diagnosis were derived. Outcomes included mortality, renal failure, and stroke. RESULTS: 26% of patients received MCS prior to transplant: 240 (4.7%) on extracorporeal membrane oxygenation (ECMO), 1,030 (20.2%) on ventricular assist device (VAD), and 54 (1%) both. 29% of patients were <1 year, and 43.8% had congenital heart disease (CHD). After adjusting for clinical characteristics, compared to no-MCS and VAD, ECMO had higher mortality during their transplant hospitalization [OR 3.97 & 2.55; 95% CI 2.43-6.49 & 1.42-4.60] while VAD mortality was similar [OR 1.55; CI 0.99-2.45]. Outcomes of ECMO+VAD were similar to ECMO alone, including increased mortality during transplant hospitalization compared to no-MCS [OR 4.74; CI 1.81-12.36]. Patients with CHD on ECMO had increased 1 year, and 10 year mortality [HR 2.36; CI 1.65-3.39], [HR 1.82; CI 1.33-2.49]; there was no difference in survival in dilated cardiomyopathy (DCM) patients based on pretransplant MCS status. CONCLUSION: Survival in CHD and DCM is similar in patients with no MCS or VAD prior to transplant, while pretransplant ECMO use is strongly associated with mortality after transplant particularly in children with CHD. In children with DCM, long term survival was equivalent regardless of MCS status.

Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders.

BACKGROUND: Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a 'low GABA marker' (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders. METHOD: Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects. RESULTS: Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype. CONCLUSIONS: These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

Effects of Border Crops and Intercrops on Control of Cucurbit Virus Diseases.

In five field trials over 3 years, control of aphid-transmitted, nonpersistent virus diseases on pumpkin, caused mostly by the potyviruses Watermelon mosaic virus (WMV) and Papaya ringspot virus type-W (PRSV-W), was achieved by intercropping with grain sorghum, as opposed to clean tillage. Reductions in disease incidence ranged from 43 to 96% (P ≤ 0.05). Surrounding pumpkin plots with borders of peanut, soybean, or corn was not effective. Borders of grain sorghum were effective, but disease control was generally less than for the intercrop treatment. Intercropping soybean and peanut with pumpkin reduced disease incidence by 27 to 60% (P ≤ 0.05), but disease control generally was less than for grain sorghum. Peak periods of alate aphid immigration generally preceded virus disease outbreaks by 7 to 14 days. However, alate landing rates, as measured in green tile traps, did not differ among treatments. Marketable yield was not increased by the intercrop treatments, and yield was reduced by up to 50% for the intercrop treatment with grain sorghum in two trials. The use of grass-selective herbicide applied along pumpkin rows, reduced seeding rates of the intercrops, or mowing did not alleviate the adverse effects of competition between pumpkin and the grain sorghum intercrop on yield.

Spatial pattern and sequential sampling of squash bug (Heteroptera: Coreidae) adults in watermelon.

Spatial distribution patterns of adult squash bugs were determined in watermelon, Citrullus lanatus (Thunberg) Matsumura and Nakai, during 2001 and 2002. Results of analysis using Taylor's power law regression model indicated that squash bugs were aggregated in watermelon. Taylor's power law provided a good fit with r2 = 0.94. A fixed precision sequential sampling plan was developed for estimating adult squash bug density at fixed precision levels in watermelon. The plan was tested using a resampling simulation method on nine and 13 independent data sets ranging in density from 0.15 to 2.52 adult squash bugs per plant. Average estimated means obtained in 100 repeated simulation runs were within the 95% CI of the true means for all the data. Average estimated levels of precision were similar to the desired level of precision, particularly when the sampling plan was tested on data having an average mean density of 1.19 adult squash bugs per plant. Also, a sequential sampling for classifying adult squash bug density as below or above economic threshold was developed to assist in the decision-making process. The classification sampling plan is advantageous in that it requires smaller sample sizes to estimate the population status when the population density differs greatly from the action threshold. However, the plan may require excessively large sample sizes when the density is close to the threshold. Therefore, an integrated sequential sampling plan was developed using a combination of a fixed precision and classification sequential sampling plans. The integration of sampling plans can help reduce sampling requirements.

Effect of temperature on efficacy of insecticides to differential grasshopper (Orthoptera: Acrididae).

The effect of temperature on activity of insecticides for controlling grasshoppers in leafy green vegetables was evaluated. Insecticides evaluated had differing modes of action and included diflubenzuron, azadirachtin, Beauveria bassiana, spinosad, endosulfan, esfenvalerate, and naled. We evaluated these insecticides for efficacy to third instars of differential grasshopper, Melanoplus differentialis (Thomas), at temperatures ranging from 10 to 35 degrees C. In the laboratory, treatment with esfenvalerate resulted in 100% mortality at temperatures of 10 to 35 degrees C, and efficacy was not temperature dependent. Treatment with spinosad resulted in similar mortality as with esfenvalerate at all temperatures except 10 degrees C. The activity of B. bassiana was greatest at 25 degrees C and was adversely affected by high and low temperatures. Treatment with diflubenzuron resulted in increased mortality at high temperatures, and at 35 degrees C its activity was similar to that of esfenvalerate and spinosad. The activity of azadirachtin ranged from 19 to 31% and was not influenced by temperature. In field studies, spinosad, diflubenzuron, and esfenvalerate provided differing levels of mortality both at application and when nymphs were exposed to 1-h-old residues. However, only spinosad and diflubenzuron provided similar levels of mortality when nymphs were exposed to 24-h-old residues. The residual activity of endosulfan, naled, esfenvalerate, and spinosad decreased with increasing time (0-24 h) after exposure to sunlight and high summer temperatures. Compared with other insecticides, naled had a short residual activity period and activity was dependent upon immediate contact with the nymphs or their substrate. B. bassiana was inactive under high temperatures and intense sunlight as occurs in summer.

Comparison of management strategies for squash bugs (Hemiptera: Coreidae) in watermelon.

Two watermelon pest management practices, a squash trap crop and a standard recommendation using soil-applied carbofuran, were compared using large-scale field plots to assess trap crop suitability as a replacement for the standard in 2000, 2001, and 2002. In both systems, foliar insecticide applications were used to control squash bugs when populations exceeded threshold levels. During 2001 and 2002, a treatment of untreated watermelon was used. Early season adult insects, from seedling to fruit set, are most critical for watermelon. Significantly fewer early adult bugs were found on watermelon in the trap crop than in the standard recommended practice in 1 of 3 yr. In both years, significantly fewer adult squash bugs were found in watermelon in the trap crop than in untreated fields. The standard recommended practice significantly reduced adult squash bugs in watermelon compared with the untreated in 1 of 2 yr. There was no significant correlation of watermelon yield and squash bug density, indicating that squash bug densities were too low to impact yield. Although squash bugs were reduced significantly by the trap crop, marketable watermelon yields were lower in the squash trap crop than in untreated watermelon, suggesting that pest management treatments may interfere with crop productivity factors other than squash bug colonization. Results suggest that mid-season production squash bug should be managed by monitoring populations and using insecticides as needed rather than using at-plant treatment. Further research is needed to compare treatments during early-season production.

The bony anatomy of clavicular malunions.

The majority of clavicle fractures heal with some degree of malunion. There has been an increased appreciation that malunion with significant shortening may lead to clinical symptoms. In a review of a large number of clavicle specimens, 73 fractures with 54 malunions were found. Distinctive patterns of malunion were identified. Shortening usually comprised a combination of overlapping and angulation of fracture fragments in a predictable fashion. An appreciation of these fracture patterns will be of interest to surgeons attempting to minimize or correct complications from such injuries.

Watermelon growth, fruit yield and plant survival as affected by squash bug (Hemiptera: Coreidae) feeding.

Adult squash bugs, Anasa tristis (De Geer) (Heteroptera: Coreidae), were confined on watermelon plants at differing phenological stages and at densities of zero to four per plant in one trial and zero to 32 per plant in three additional trials. Squash bugs were allowed to feed on the plants until plants died or fruit matured. Plant foliage, roots, and fruit were harvested and weighed to determine effects on growth and productivity. Growth and fruit production was regressed on number of squash bugs and results indicated that an increasing density of squash bugs feeding on vining and flowering stage plants resulted in significant reductions in plant growth and fruit yield. When plants were infested at the fruit set stage of growth, there was either less effect or no effect on plant growth and fruit production. Plant mortality increased as the density of squash bugs increased regardless of the stage of growth when plants were infested with squash bugs.

Watermelon seedling growth and mortality as affected by Anasa tristis (Heteroptera: Coreidae).

Adult squash bugs, Anasa tristis (De Geer), were confined on seedling watermelon plants at densities of zero, one, two, and four per plant. Squash bugs were allowed to feed on the plants until plants died or reached 30 cm in height. Number of leaves and length of plant vine were recorded at 2- or 3-d intervals. Seedling foliage, stems, and roots were harvested and dried after plants reached 30 cm in height. Growth of seedlings was regressed on number of squash bugs and results indicated that an increasing density of squash bugs feeding on seedlings resulted in a significant reduction in plant growth. Additionally, increased density of squash bugs resulted in reduced weight of foliage and root dry biomass. Seedling mortality increased as the density of squash bugs increased.

Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common, progressive respiratory disease that causes great morbidity and mortality despite treatment. There is evidence for airway inflammation in COPD. Cilomilast is an orally active, potent, selective phosphodiesterase type 4 inhibitor, which in vitro can affect cells thought to be of clinical importance in COPD. Our aim was to assess the safety, efficacy, and dose response of cilomilast in the treatment of patients with this disease. METHODS: We did a 6-week, randomised, dose-ranging study in 424 patients with COPD (forced expiratory volume in 1 s [FEV(1)] 46.8% of predicted, FEV(1)/forced vital capacity [FVC] 54.6%, and postsalbutamol reversibility 5.4%). We randomly assigned individuals at 60 European centres to receive cilomilast 5 (n=109), 10 (n=102), or 15 (n=107) mg twice daily, or placebo (n=106). The main outcome measure was trough FEV(1) before and after use of a bronchodilator. Analyses were by intention to treat. FINDINGS: Cilomilast 15 mg twice daily significantly improved FEV(1) compared with placebo (mean 130 mL vs -30 mL [95% CI 90-240] at week 6, p<0.0001). FVC and peak expiratory flow were also improved (p=0.001 and p<0.0001, respectively). Quality of life measures did not differ significantly between the groups. There were no significant differences in serious adverse events between the groups. INTERPRETATION: Cilomilast 15 mg twice daily might be an effective maintenance treatment for COPD. Further clinical studies are underway.

Expanding the epidemiologic profile: risk factors for active tuberculosis in people immigrating to Ontario.

BACKGROUND: Many people immigrating to Canada come from countries with a high burden of tuberculosis. The aim of this study was to develop a detailed epidemiologic profile of foreign-born people with tuberculosis living in Ontario. METHODS: In this population-based case-control study, cases of tuberculosis diagnosed in 1994-1995 were identified from the database of the Ontario Reportable Disease Information Service and were considered eligible for analysis if a record of landing (receipt of permission to establish residence in Canada) from the period 1986-1995 was found in the Citizenship and Immigration Canada (CIC) database, if the person was at least 11 years of age at the time their visa was issued, and if the person had not been diagnosed with tuberculosis before becoming legally landed in Canada. Control subjects, who met the same criteria as the case subjects but who did not have tuberculosis in 1994-1995, were identified from a CIC database for landed immigrants. RESULTS: A total of 1341 cases of tuberculosis in foreign-born people were reported in Ontario in 1994-1995. A record of landing was found in CIC databases for 1099 of these people, 224 of whom were not legally landed at the time of diagnosis. In total, 602 cases met the inclusion criteria. The 2 strongest determinants of risk among those who had become landed within the preceding 10 years were referral for medical surveillance by immigration officials (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.6-6.0) and world region of origin (Somalia [OR 67.7, 95% CI 31.3-154.9], Vietnam [OR 25.0, 95% CI 12.5-50.0], the Philippines [OR 11.9, 95% CI 6.0-23.3], other sub-Saharan African countries [OR 11.6, 95% CI 5.7-23.2], India [OR 9.7, 95% CI 4.9-18.9], China [OR 6.1, 95% CI 3.1-12.1], other Asian countries [OR 4.7, 95% CI 2.4-9.1], the Middle East [OR 4.1, 95% CI 2.0-8.3], Latin America [OR 1.9, 95% CI 0.9-3.8), and the former socialist countries of Europe [OR 1.8, 95% CI 0.8-3.8]; the reference category was countries with established market economies). Low socioeconomic status was an independent risk factor. INTERPRETATION: The risk of tuberculosis in groups of people migrating to Ontario is highly variable and is influenced by several factors. Successful population-based tuberculosis prevention strategies will need to accommodate this variability.

Production of tumour necrosis factor alpha by primary cultured rat alveolar epithelial cells.

Tumour necrosis factor alpha(TNF-alpha) is one of the most important pro-inflammatory cytokines, which plays an important role in host defense and acute inflammation related to tissue injury. The major source of TNF-alpha has been shown to be immune cells such as macrophages and neutrophils. In the present study, we demonstrated that LPS-treatment on alveolar epithelial cells isolated from adult rat lungs also induced a dose- and time-dependent release of TNF-alpha. The purity and identity of these cells were examined by immunofluorescent staining and confocal microscopy with antibodies for cytokeratin and pro-surfactant protein C, markers for epithelial cells and type II pneumocytes respectively. Positive staining of TNF-alpha was observed throughout the cell layer and localized intracellularly. LPS-induced TNF-alpha production from alveolar epithelial cells was blocked not only by cycloheximide, an inhibitor of protein translation, but also by actinomycin D, an inhibitor of gene transcription. The mRNA of TNF-alpha rapidly increased within 1 h of LPS stimulation. These data suggest that LPS-induced TNF-alpha production from alveolar epithelial cells is primarily regulated at the transcriptional level, which is different from that of macrophages and neutrophils. TNF-alpha produced by alveolar epithelial cells may function as an alert signal in host defense to induce production of other inflammatory mediators.

Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation.

Pycnodysostosis (Pycno) is an autosomal recessive osteosclerotic skeletal dysplasia that is caused by the markedly deficient activity of cathepsin K. This lysosomal cysteine protease has substantial collagenase activity, is present at high levels in osteoclasts, and is secreted into the subosteoclastic space where bone matrix is degraded. In vitro studies revealed that mutant cathepsin K proteins causing Pycno did not degrade type I collagen, the protein that constitutes 95% of organic bone matrix. To determine the in vivo effects of cathepsin K mutations on bone metabolism in general and osteoclast-mediated bone resorption specifically, several bone metabolism markers were assayed in serum and urine from seven Pycno patients. Two markers of bone synthesis, type I collagen carboxy-terminal propeptide and osteocalcin, were normal in all Pycno patients. Tartrate-resistent acid phosphatase, an osteoclast marker, was also normal in these patients. Two markers that detect type I collagen telopeptide cross-links from the N and C termini, NTX and CTX, respectively, were low in Pycno. A third marker which detects a more proximal portion of the C terminus of type I collagen in serum, ICTP, was elevated in Pycno, a seemingly paradoxical result. The finding of decreased osteoclast-mediated type I collagen degradation as well as the use of alternative collagen cleavage sites by other proteases, and the accumulation of larger C-terminal fragments containing the ICTP epitope, established a unique biochemical phenotype for Pycno.

Attachment style, traumatic bonding, and developing relational capacities in a long-term trauma group for women.

Adults with histories of severe childhood abuse often experience considerable difficulties with interpersonal trust. At the same time, they may strongly desire to be less alone with the painful aftereffects of their traumatic pasts. Psychotherapy groups have often been recommended as important components of treatment for reducing survivors' feelings of isolation and shame. We propose that an understanding of attachment styles and of traumatic bonding helps to clarify the specific manifestations of interpersonal distrust as they may emerge in a survivors' group. In addition, we suggest guidelines for determining what kind of group may be appropriate for a given individual at a particular point in treatment.

The future of health care, Part 2. The PPMC debate. Panel discussion.

In Part 2 of this second annual panel discussion, Jeff Goldsmith, Barbara LeTourneau, Uwe Reinhardt, and physician executives from three physician practice management companies (PPMCs) examine this burgeoning new industry. They grapple with questions (and occasionally with each other), such as: Are PPMCs delivering what they promise? What will separate successful PPMCs from the rest? When PPMCs win, who loses? What value do PPMCs add to health care? What lies ahead for this industry? Could Wall Street pressure cause PPMCs to put profit ahead of physicians and patients? And, what roles will physician executives play in PPMCs?

Effects of the stress response in septic rats and LPS-stimulated alveolar macrophages: evidence for TNF-alpha posttranslational regulation.

We have previously demonstrated that induction of the stress response, by heat stress or sodium arsenite, administered 18 h before initiation of sepsis in rats, significantly decreased mortality and lung injury. As a possible mechanism underlying this effect, we hypothesized that the induction of the stress response, prior to bacterial endotoxin (lipopolysaccharide, LPS) stimulation, would cause a decrease in synthesis and/or release of tumor necrosis factor-alpha (TNF-alpha), making the animals more resistant to sepsis. Rats exposed to Salmonella typhosa LPS demonstrated a rise in plasma TNF-alpha. In contrast, rats exposed to heat stress or to sodium arsenite 18 h prior to LPS had significantly lower levels of plasma TNF-alpha. To examine the mechanisms by which the stress response mediates this decrease, we studied cultured alveolar macrophages. Similar to in vivo studies, TNF released into supernatants of alveolar macrophages treated with LPS was significantly higher than from cells exposed to the stress response prior to LPS. The decrease in TNF-alpha protein release was not accompanied by a similar decrease in TNF-alpha mRNA levels or by a decrease in cell-associated TNF-alpha, suggesting possible posttranslational regulation of TNF-alpha. To determine whether the decrease in TNF-alpha release was due to binding and sequestration by heat shock proteins (HSP), TNF-alpha was purified by immunoprecipitation. Under these conditions, TNF-alpha and HSP72kDa coprecipitated from cells that had received stress treatment prior to LPS. These data implicate HSP in posttranslational control of TNF-alpha release in LPS-stimulated alveolar macrophages exposed to the stress response.

Bony changes of the glenoid as a consequence of shoulder instability.

Among 500 skeletons of mature individuals, 27 showed signs of shoulder instability as indicated by the presence of a glenoid rim avulsion fracture, a bony Bankart lesion, with an anterior or posterior Hill-Sachs defect. Twenty-two of these glenoid lesions were anterior, and five were posterior. This is a higher prevalence than reported in clinical studies. With few exceptions the pathologic changes in the bony glenoid were well circumscribed and not found in conjunction with diffuse arthritic changes. These findings do not support prophylactic shoulder stabilization to avoid the development of arthritic changes of a generalized and major degree.