Platypnea Orthodeoxia Due to a Patent Foramen Ovale and Intrapulmonary Shunting After Severe COVID-19 Pneumonia.

BACKGROUND Platypnea orthodeoxia syndrome (POS) presents with positional dyspnea and hypoxemia defined as arterial desaturation of at least 5% or a drop in PaO2 of at least 4 mmHg. Causes of POS include a variety of cardiopulmonary etiologies and has been reported in patients recovering from severe COVID-19 pneumonia. However, clinical presentation and outcomes in a patient with multiple interrelated mechanisms of shunting has not been documented. CASE REPORT An 85-year-old man hospitalized for hypertensive emergency and severe COVID-19 pneumonia was diagnosed with platypnea orthodeoxia on day 28 of illness. During his disease course, the patient required supplemental oxygen by high-flow nasal cannula but never required invasive mechanical ventilation. Chest imaging revealed evolving mixed consolidation and ground-glass opacities with a patchy and diffuse distribution, involving most of the left lung. Echocardiography was ordered to evaluate for intracardiac shunt, which revealed a patent foramen ovale. Closure of the patent foramen ovale was not pursued. Management included graded progression to standing and supplemental oxygen increases when upright. The patient was discharged to a skilled nursing facility and his positional oxygen requirement resolved on approximately day 78. CONCLUSIONS The present case highlights the multiple interrelated mechanisms of shunting in patients with COVID-related lung disease and a patent foramen ovale. Eight prior cases of POS after COVID-19 pneumonia have been reported to date but none with a known patent foramen ovale. In patients with persistent positional oxygen requirements at follow-up, quantifying shunt fraction over time through multiple modalities can guide treatment decisions.

Downregulation of CD40L-CD40 attenuates seizure susceptibility and severity of seizures.

Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40-CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate seizures and status epilepticus (SE) respectively. In mice, anti-CD40L antibody was administered intranasally before PTZ. Brain samples from human TLE and post-seizure mice were processed to determine CD40-CD40L expression using histological and molecular techniques. CD40 expression was higher in hippocampus from human TLE and in cortical neurons and hippocampal neural terminals after experimental seizures. CD40-CD40L levels increased after seizures in the hippocampus and in the cortex. After SE, CD40L/CD40 levels increased in cortex and showed an upward trend in the hippocampus. CD40KO mice demonstrated reduction in seizure severity and in latency compared to WT mice. Anti-CD40L antibody limited seizure susceptibility and seizure severity. CD40L-CD40 interaction can serve as a target for an immuno-therapy for TLE.

Barrett's oesophagus and oesophageal cancer following oesophageal atresia repair: a systematic review.

BACKGROUND: Concern exists that patients born with oesophageal atresia (OA) may be at high risk for Barrett's oesophagus (BO), a known malignant precursor to the development of oesophageal adenocarcinoma. Screening endoscopy has a role in early BO identification but is not universal in this population. This study aimed to determine prevalence of BO after OA repair surgery, to quantify the magnitude of this association and inform the need for screening and surveillance. METHODS: A systematic review, undertaken according to PRISMA guidelines, was preregistered on PROSPERO (CRD42017081001). PubMed and EMBASE were interrogated using a standardized search strategy on 31 July 2020. Included papers, published in English, reported either: one or more patients with either BO (gastric/intestinal metaplasia) or oesophageal cancer in patients born with OA; or long-term (greater than 2 years) follow-up after OA surgery with or without endoscopic screening or surveillance. RESULTS: Some 134 studies were identified, including 19 case reports or series and 115 single- or multi-centre cohort studies. There were 13 cases of oesophageal cancer (9 squamous cell carcinoma, 4 adenocarcinoma) with a mean age at diagnosis of 40.5 (range 20-47) years. From 6282 patients under long-term follow-up, 317 patients with BO were reported. Overall prevalence of BO was 5.0 (95 per cent c.i. 4.5 to 5.6) per cent, with a mean age at detection of 13.8 years (range 8 months to 56 years). Prevalence of BO in series reporting endoscopic screening or surveillance was 12.8 (95 per cent c.i. 11.3 to 14.5) per cent. CONCLUSION: Despite a limited number of cancers, the prevalence of BO in patients born with OA is relatively high. While limited by the quality of available evidence, this review suggests endoscopic screening and surveillance may be warranted, but uncertainties remain over the design and effectiveness of any putative programme.

Obturator hernia: a case report.

BACKGROUND: Obturator hernia is rare and accounts for less than 1% of all abdominal wall hernias. It represents a diagnostic challenge due to its nonspecific signs and symptoms. CASE PRESENTATION: We present a case of an 89-year-old caucasian female with a 12-hour history of right medial thigh pain. Computed tomography scan revealed a right obturator hernia with small bowel obstruction. The hernia was successfully repaired laparoscopically without any need for small bowel resection. She was discharged on postoperative day 2 with an uneventful recovery and zero complications. CONCLUSION: This case report highlights the importance of rapid diagnosis and repair of obturator hernia even in the setting of an improving clinical picture. It also demonstrates the safety of laparoscopic repair in this setting.

Clonal diversity and spatial genetic structure in the long-lived herb, Prairie trillium.

Combining population genetic studies with demographic surveys in long-lived clonal herbs can yield insight into the population dynamics of clonal plant populations. In this study, we assayed clonal diversity and spatial genetic structure in a population of a long-lived understory herb, Trillium recurvatum, that has been the focus of a demographic study spanning 26 years at the Meeman Biological Station in Memphis, Tennessee, USA. Using a set of five newly developed simple sequence repeat markers first reported here, we assessed 1) the extent of clonal diversity within the Meeman site, 2) the degree to which genetic diversity varies with stage class (juvenile, non-flowering, and flowering adults) at this site, 3) whether there is spatial genetic structure at the Meeman site, and 4) how measures of genetic diversity and inbreeding at the Meeman site compare to two additional nearby populations. Along with these analyses, we calculated and compared traditional population genetic metrics with information theory-based diversity indices. Although clonal propagation was present, the focal population displayed moderate levels of clonal diversity comprising 81 genets from the 174 individuals sampled. In the focal site, we also found that genetic diversity was highest in the flowering stage class when compared to the non-flowering and juvenile classes. We report that genets exhibited spatial genetic structure in the focal site exhibiting values for the Sp statistic of 0.00199 for linear distance and 0.0271 for log distance. Measures of unbiased gene diversity and the inbreeding coefficient were comparable across the sampled populations. Our results provide complementary genetic data to previous demographic studies in T. recurvatum, and these findings provide data for future studies aimed at integrating the degree of clonality, genetic variation, and population dynamics in this species. Our findings suggest that T. recurvatum at the focal Meeman site displays higher levels of sexual reproduction than were previously suggested, and spatial genetic structure estimates were comparable to other plant species with mixed and outcrossing mating strategies.

Trace metal contamination of the aquatic plant Hydrilla verticillata and associated sediment in a coastal Alabama creek (Gulf of Mexico-USA).

The objectives of this study were to (i) assess trace metal concentrations in Hydrilla verticillata and sediment from an estuarine creek in Alabama (USA), where high metal levels in biota were previously reported, and (ii) investigate the relationship between metal concentrations in H. verticillata and the sediment compartment. Our results indicate that sediment and H. verticillata exhibit moderate metal concentrations in the study area. We found that levels in plant tissues can be up to five times higher than in the sediment (e.g., Cd), suggesting that H. verticillata can take up and store several trace metals (Cd, Hg, Ni, and Zn) from this compartment. Together with studies focused on the uptake and accumulation of trace metals from the surrounding water, laboratory- and field-based studies are needed to better evaluate this plant's ability to acquire metals from the sediment that constitutes a contaminant sink in human-impacted coastal regions.

Comparison of morphology and photo-physiology with metal/metalloid contamination in Vallisneria neotropicalis.

The overarching goal of this in situ study was to investigate the integrated impact(s) that metal/metalloid contamination might have on the overall health and performance of the ecologically important aquatic macrophyte, Vallisneria neotropicalis. Morphological (i.e., shoot growth-based endpoints) and photo-physiological (i.e., photosynthetic activity measured as chlorophyll a fluorescence and oxygen exchange) variables, along with aboveground tissue metal/metalloid concentrations, were measured in natural populations of V. neotropicalis that differed with respect to their anthropogenic pressure. With the exception of an overall negative effect on growth, our results suggest that there were no detrimental effects of low/moderate contamination of V. neotropicalis by trace elements (i.e., arsenic As and mercury Hg; 1.04-2.77 µg g(-1) dry wt. and 3.76-15.18 ng g(-1) dry wt., respectively) on the photosynthetic physiological performance of this species. V. neotropicalis appears to tolerate low/moderate levels of trace element contamination with little impact on plant health and performance.

Arsenic and mercury bioaccumulation in the aquatic plant, Vallisneria neotropicalis.

Arsenic (As) and mercury (Hg) are among the most toxic metals/metalloids. The overall goal of this study was to investigate the bioaccumulation of these trace elements in Vallisneria neotropicalis, a key trophic species in aquatic environments. For this purpose, As and Hg concentrations were determined in sediments and natural populations of V. neotropicalis in sub-estuaries of Mobile Bay (Alabama, USA), differing with respect to past and present anthropogenic impact. Analyses indicate that the Fish River is the most contaminated among the sub-estuaries investigated; levels of As found in Fish River sediments fall within a range that could potentially cause adverse effects in biota. Sediment As concentrations were only moderately correlated with those in V. neotropicalis; no correlation was found between sediment and plant Hg levels. However, several parameters could have masked such potential relationships (e.g., differences in sediment characteristics and "biological dilution" phenomena). Results presented herein highlight the numerous parameters that can influence metal/metalloids accumulation in aquatic plants as well as species-specific responses to trace element contamination. Finally, this study underscores the need for further investigation into contaminant bioaccumulation in ecologically and economically important coastal environments.

Role of patient education level in predicting macrosomia among women with gestational diabetes mellitus.

OBJECTIVE: To evaluate the role of education level in predicting the risk of macrosomia among women with gestational diabetes mellitus. STUDY DESIGN: Women with gestational diabetes, who were referred to the California Diabetes and Pregnancy Sweet Success Program between June 2001 and December 2002, were included in the study. Multiple logistic regression was used estimate the risk of macrosomia, defined as a birth weight >4000 g. RESULTS: Compared to college-educated women, high school- and middle school-educated women were 21% (relative risk (RR), 1.21; 95% confidence intervals (CI), 1.01-1.44) and 35% (RR, 1.35; 95% CI, 1.09-1.70) more likely to deliver a macrosomic infant, respectively. CONCLUSION: Gestational diabetics with a lower level of educational attainment appear to have an increased risk of macrosomia. Future studies are necessary to determine whether this finding reflects a variation in adherence to recommended treatments by education/literacy level, or if it is a surrogate marker for intrinsic, biological differences or differences in lifestyle.

Nuclear ribosomal DNA internal transcribed spacer 1 (ITS1) in Picea (Pinaceae): sequence divergence and structure.

The nrDNA ITS1 of Picea is 2747-3271 bp, the longest known of all plants. We obtained 24 cloned ITS1 sequences from six individuals of Picea glehnii, Picea mariana, Picea orientalis, and Picea rubens. Mean sequence divergence within these individuals (0.018+/-0.009) is more than half that between the species (0.031+/-0.011) and may be maintained against concerted evolution by separation of Picea 18S-26S rDNA repeats on multiple chromosomes. Picea ITS1 contains three subrepeats with a motif (5'-GGCCACCCTAGTC) that is conserved across Pinaceae. Two subrepeats are tandem, remote from the third, and more closely related and significantly more similar to one another than either is to the third subrepeat. This correlation between similarity and proximity may be the result of subrepeat duplication or concerted evolution within rDNA repeats. In inferred secondary structures, subrepeats generally form long hairpins, with a portion of the Pinaceae conserved motif in the terminal loop, and tandem subrepeats pair with one another over most of their length. Coalescence of ITS1 sequences occurs in P. orientalis but not in the other species.

Interleukin-1beta stimulation of c-Jun NH(2)-terminal kinase activity in insulin-secreting cells: evidence for cytoplasmic restriction.

Cytokines have been shown to have dramatic effects on pancreatic islets and insulin-secreting beta-cell lines. It is well established that cytokines such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and gamma-interferon (IFN-gamma) inhibit beta-cell function and are cytotoxic to human and rodent pancreatic islets in vitro. Despite the pleiotropic effects of cytokines on beta-cells, the specific signal transduction pathways and molecular events involved in beta-cell dysfunction remain largely unresolved. In this report, we have examined IL-1beta stimulation of c-Jun NH(2)-terminal kinase (JNK) activity in insulin-secreting clonal cell lines. We demonstrate that IL-1beta transiently activates 46- and 54-kDa isoforms of JNK in cultured RINm5F beta-cells. Furthermore, IL-1beta stimulation of JNK activity is specific, because TNF-alpha and IFN-gamma were without effect. Stable overexpression of JNK1 in RINm5F cells increased levels of activated JNK without affecting kinase activity. JNK-interacting protein (JIP) associates with endogenous as well as overexpressed JNK, suggesting that JIP may serve to regulate JNK activity. Finally, we demonstrate that activated JNK is fully retained in cytoplasmic and membrane compartments without any nuclear translocation. Together, these data indicate that IL-1beta-stimulated JNK activity may be distinctly targeted to cytoplasmic and/or membrane compartments in clonal insulin-producing cells, and that JIP may serve to localize JNK activity to specific substrates.

Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation.

BACKGROUND: Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal. METHODS: An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls. RESULTS: Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months. CONCLUSIONS: Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.

Estimating the size of hard-to-reach populations: a novel method using HIV testing data compared to other methods.

OBJECTIVE: To estimate population size of hard-to-reach groups such as injecting drug users and men who have sex with men. DESIGN: Several different methods were used to estimate the size of these populations in Canada's three largest cities (Toronto, Montreal and Vancouver). METHODS: A novel method (referred to as the indirect method) was developed for use in Toronto and Vancouver that combines HIV serodiagnostic information with data on HIV testing behavior. Population size estimates were obtained by dividing the number of injecting drug users or men who have sex with men recorded in HIV serodiagnostic databases in a given year by the proportion of the corresponding group that reported being tested in a 1-year period. Results of this method were compared with four other methods: (1) population surveys; (2) capture-recapture (for injecting drug users only); (3) a modified Delphi technique; and (4) a method based on the proportion of never-married men aged 45 and over (for men who have sex with men only). Only these other methods were used in Montreal. RESULTS: The survey method gave the lowest estimates which are best viewed as minimum estimates given the relative inability of surveys to access these populations and the reluctance of participants to admit to sensitive behaviors. The indirect method produced results more closely comparable with those obtained by other methods, but they are probably slight overestimates, at least for injecting drug users, due to possible underestimation of the proportion tested for HIV. Point estimates using the indirect method were 17,700 and 17,500 for injecting drug users in Toronto and Vancouver, respectively, and 39,100 and 15,900 for men who have sex with men. In Toronto, results for the other methods ranged from 12,300-13,360 for injecting drug users and 18,800-35,000 for men who have sex with men. For Vancouver, these ranges were 6400-11,670 and 7000-26,500, respectively. In Montreal, ranges were 4300-12,500 for injecting drug users and 18,500-40,000 for men who have sex with men. CONCLUSIONS: This novel method provides estimates of population size of hard-to-reach groups such as injecting drug users and men who have sex with men that are comparable with results derived by other methods. These estimates may be useful for the purposes of planning, implementing and evaluating prevention and care services, especially when they are combined with the results of other estimation methods to improve the degree of confidence in the resulting estimates.

A comparison of echocardiography and pulmonary artery catheterization for evaluation of pulmonary artery pressures in pregnant patients with suspected pulmonary hypertension.

OBJECTIVE: This study was undertaken to compare the accuracy of echocardiography versus pulmonary artery catheterization to estimate pulmonary artery pressures in pregnant women with suspected pulmonary hypertension. STUDY DESIGN: A retrospective chart review was performed between January 1990 and February 2000 for all pregnant patients with cardiac disease. Patients with pulmonary artery pressure values estimated by cardiac catheterization and echocardiography during pregnancy were included. Pulmonary hypertension is defined as pulmonary artery systolic pressure >30 mm Hg. RESULTS: Twenty-seven patients were included in the study. There was a significant overestimation of the mean pulmonary artery pressure with echocardiography compared with catheterization (55.4 vs 51.1 mm Hg; P <.005). Of the 20 patients, pulmonary artery pressure was significantly greater when estimated by echocardiography than when measured by catheterization (59.6 vs 54.8 mm Hg; P <.004). Thirty-two percent (8/25) of the patients had pulmonary hypertension when estimated by echocardiography but had normal pulmonary artery pressures on subsequent catheterization. CONCLUSION: Echocardiography significantly overestimated pulmonary artery pressures compared with catheterization in pregnant patients with suspected pulmonary hypertension. Patients with structural cardiac defects appear to have a significantly greater difference in pulmonary artery pressures. Thirty-two percent of pregnant patients with normal pulmonary artery pressures may be misclassified as having pulmonary artery hypertension when measured by echocardiography alone.

Safety of the Canadian blood supply in 1980-85: using a paediatric cohort for risk assessment of human immunodeficiency virus (HIV) infection.

The risk of HIV from transfusions in Canada in the period 1980-85 was estimated, using the information from a transfused paediatric cohort. Children who were transfused between January 1980 and November 1985 at a tertiary care paediatric hospital were contacted by letter. With this notification, HIV testing for recipients was recommended. HIV testing histories were obtained. The number tested for HIV was estimated from the questionnaire responses and from data matching with the HIV-testing laboratory. Cases of HIV infection were identified through multiple sources. In this cohort, 11,028 children were transfused a mean of 21 units. Of the 10,220 living recipients, the estimated proportion tested for HIV was 86% to 91%. Thirty-one cases of HIV infection were identified, representing 0.28% of the cohort but 0.34% of those expected to have been tested. The estimated HIV incidence per 1,000 units transfused ranged from 0.028 [95% CI 0.0007, 0.155] in 1980 to 0.445 [95% CI 0.2592, 0.712] in 1985. This suggests that the risk of HIV from transfusions in Canada continued to rise until the implementation of HIV testing of donors in November 1985.

Controversial and special situations in the management of preterm premature rupture of membranes.

The management of preterm premature rupture of membranes is one of the many controversial areas of medicine. Many of the protocols used to manage preterm premature rupture of membranes are not based on solid data. Other situations are rarely encountered, making it very difficult to arrive at a management scheme on which all can agree. This article presents five such areas along with available literature and discusses treatment options involving these controversial or special topics.

Accuracy of self-monitoring of blood glucose: impact on diabetes management decisions during pregnancy.

PURPOSE: This study tested the hypothesis that the accuracy of self-monitoring of blood glucose (SMBG) values of patients with diabetes during pregnancy deviates substantially from reference values. METHODS: The patients' glucose values were measured on 6 different SMBG meters; reference values were from the HemoCue B Glucose Analyzer. Over a 5-year period, 1973 comparisons between SMBG values and reference values were recorded during clinic visits and used for this study. Data were analyzed for percent of values that varied more than +/- 10.5% and +/- 15.5% from the reference value. Out-of-range data at each variance level were analyzed to determine the impact on medical management if decisions were based solely on SMBG values. RESULTS: One third of SMBG readings deviated significantly, which could adversely affect treatment for half of these patients if diabetes management was based on SMBG values. At the 10.5% deviation level, 34% of SMBG meter readings were out of range; 54% of these would have implied erroneous treatment. At the 15.5% deviation level, 18% were out of range; 63% of these would have implied erroneous management. CONCLUSIONS: The accuracy of home meters should be verified at regular intervals, and SMBG values should not be the sole criterion for diabetes management during pregnancy.