Excision of Deep Rectovaginal Endometriosis Nodules with Large Infiltration of Both Rectum and Vagina: What Is a Reasonable Rate of Preventive Stoma? A Comparative Study.
To compare postoperative complications and rectovaginal fistula rate in women undergoing excision of large rectovaginal endometriosis requiring concomitant excision of rectum and vagina during 2 time periods with differing policies for preventive stoma confection. Retrospective before-and-after comparative cohort study on data prospectively recorded in a database. Patients managed from September 2018 to March 2020 (first period) were compared with those managed from April 2020 to June 2022 (second period). Endometriosis Institute. One hundred sixty-eight patients presenting with deep endometriosis infiltrating the rectum and vagina, with lesions more than 3 cm in diameter during 2 consecutive time periods with differing policies regarding use of preventive stoma. Rectal disc excision or colorectal resection, concomitantly with large vaginal excision. A total of 87 and 81 women received surgery during the first and the second period, respectively, during which the rate of preventive stoma was, respectively, 32.2% and 8.6%. Deep rectovaginal nodule characteristics were comparable. The mean height (SD) of rectal sutures after disc excision and colorectal resection were, respectively, 6.5 cm (2.3 cm) and 7.2 cm (3.8 cm). Rectovaginal fistula was recorded in 17 patients, corresponding to an overall rate of 10.1%. The rates of rectovaginal fistula in the group of patients with and without preventive stoma, regardless of the period in which surgery was performed, were 11.4% and 9.8%, respectively (p = .76). The rates of fistula recorded during the first and the second period were, respectively, 9.2% and 11.1% (p = .80), and that of overall early main complications were 31% and 29.6% (p = .84). Regression logistic model identified an independent relationship between smoking and rectovaginal fistula (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.1-14) after adjustment for the period (adjusted OR 1.4, 95% CI 0.4-4.9 related to the second period), stoma confection (adjusted OR 1.8, 95% CI 0.5-7.1 related to stoma confection), robotic surgery (adjusted OR 1.7, 95% CI 0.3-10.1 related to robotic assistance), and type of rectal surgery (adjusted OR 0.4, 95% CI 0.1-1.4 related to disc excision when compared with colorectal resection). No statistically significant differences were found concerning risk of rectovaginal fistula in women with rectovaginal endometriosis requiring large rectal and vaginal excision after a decision to no longer routinely perform preventive stoma.


Cyclization of an α,β-unsaturated hydrazone catalyzed by a BINOL-phosphoric acid: Pericyclic or not?
Density functional theory is used to study the mechanism of the title reaction, one of the first catalytic asymmetric 6π-electrocyclizations observed experimentally. The benzylideneacetone-derived phenyl hydrazone is chosen as model substrate for the cyclization reaction, both in the protonated (A) and unprotonated (B) form, while the isoelectronic carbon analogue, 1,5-diphenylpentadienyl anion (C), serves as a reference for comparisons. The barrier to cyclization is computed to be more than 15 kcal/mol lower in A compared with B, in line with the observed acid catalysis. The relevant transition states to cyclization are characterized for A and C using orbital inspection, natural bond orbital analysis, nucleus independent chemical shifts, and stereochemical indicators. The cyclization of C is confirmed to be pericyclic, while that of A can be described as pseudopericyclic ring closure involving an intramolecular nucleophilic addition.


Response2covid19, a dataset of governments' responses to COVID-19 all around the world.
Following the COVID-19 outbreak, governments all around the world have implemented public health and economic measures to contain the spread of the virus and to support the economy. Public health measures include domestic lockdown, school closures and bans on mass gatherings among others. Economic measures cover wage support, cash transfers, interest rates cuts, tax cuts and delays, and support to exporters or importers. This paper introduces 'Response2covid19', a living dataset of governments' responses to COVID-19. The dataset codes the various policy interventions with their dates at the country-level for more than 200 countries from January 1 to October 1, 2020 and is updated every month. The production of detailed data on the measures taken by governments can help generate robust evidence to support public health and economic decision making.


Performance evaluation of a continuous packed bed bioreactor: Bio-kinetics and external mass transfer study.
The biodegradation of naphthalene using low-density polyethylene (LDPE) immobilized Exiguobacterium sp. RKS3 (MG696729) in a packed bed bioreactor (PBBR) was studied. The performance of a continuous PBBR was evaluated at different inlet flow rates (IFRs) (20-100 mL/h) under 64 days of operation. The maximum naphthalene removal efficiency (RE) was found at low IFR, and it further decreased with increasing IFRs. In a continuous PBBR, the external mass transfer (EMT) aspect was analysed at various IFRs, and experimental data were interrelated between Colburn factor (JD) and Reynolds number (NRe) as [Formula: see text] . A new correlation [Formula: see text] was obtained to predict the EMT aspect of naphthalene biodegradation. Andrew-Haldane model was used to evaluate the bio-kinetic parameters of naphthalene degradation, and kinetic constant νmax, Js, and Ji were found as 0.386 per day, 13.6 mg/L, and 20.54 mg/L, respectively.


Noise robust automatic heartbeat classification system using support vector machine and conditional spectral moment.
Heartbeat classification is central to the detection of the arrhythmia. For the effective heartbeat classification, the noise-robust features are very significant. In this work, we have proposed a noise-robust support vector machine (SVM) based heartbeat classifier. The proposed classifier utilizes a novel noise-robust morphological feature which is based on the conditional spectral moment (CSM) of the heartbeat. In addition to the proposed CSM feature, we have also employed the existing RR interval, the wavelets, and the higher-order statistics (HOS) based temporal and morphological feature sets. The noise-robustness test of the proposed CSM and all the studied feature sets is performed for the SVM based heartbeat classifier. Further, we have studied the significance of combining these temporal and morphological features on the final classification performance. For this purpose, the individual SVMs were trained for each of the feature set. The final classification is based on the ensemble of these individual SVMs. Various combining scheme such as sum, majority, and product rules are employed to ensemble the result of the individually trained SVMs. The experimental results show the noise-robustness of the proposed CSM feature. The proposed classifier gives improved overall performance compared to the existing heartbeat classification systems.


[On eye changes associated with the pigmented spots syndrome (Peutz-Jeghers) (author's transl)].
After a survey of cases of the pigmentpolyposis (Peutz-Jeghers) in the literature reported, a woman with an abortive form of this syndrome (pigmentanomaly ) and a bilateral embryotoxon posterius (Axenfeld) is described. Both signs are heritable in the autosomal-dominant manner. The association of pigmentpolyposis and embryotoxon is not yet observed. Possibly there is present a new-mutation. The examination of the family detected no other special cases. For the future on had in cases of pigmentpolyposis possible ocular changes more in view than till now.


Elimination of furosemide in healthy subjects and in those with renal failure.
Furosemide was administered intravenously to 5 healthy volunteers and 15 patients with various degrees of renal failure. Two patients were given the drug orally. The plasma half-life of furosemide averaged 0.79 hr in the healthy subjects. Although most patients with kidney disease had a prolonged half-life (t1/2), up to 24.58 hr, some with advanced renal failure had an almost normal t1/2. The plasma clearance of furosemide, which in the normal subjects averaged 194 ml/min, decreased proportionally with decreasing creatinine clearance, as did the renal clearance, which in the healthy subjects averaged 95 ml/min. There was no correlation between kidney function and the apparent volume of distribution or of nonrenal clearance. One patient was given 35S-labeled furosemide intravenously. Although the furosemide plasma t1/2 was essentially normal, the elimination rate of metabolites was decreased. Unlike that of healthy subjects, the main route of excretion of label was in the feces.


Surgical treatment of isolated abdominal wall metastasis in colorectal cancer.
Isolated abdominal wall recurrence, following resection of a primary large bowel adenocarcinoma, is an infrequent finding. Over a ten year period, 22 patients were submitted to en bloc resection of such localized neoplastic foci. In 13 cases, recurrent tumor was located in a previous midline or para median incision. Nine patients underwent palliative radiotherapy and/or chemotherapy once the recurrent disease was identified, and were operated on when uncontrolled progression was clinically evident. In all cases, 4-5 cm disease-free margins were obtained. In eight patients it was possible to close the defect primarily and 14 patients required marlex mesh. Twelve patients were alive at two years and ten patients at five-years follow-up mark. Mucin-producing or poorly differentiated adenocarcinoma had the worse prognosis. Synthetic prosthesis allowed for adequate resections with little morbidity and acceptable cosmesis. Symptomatic relief and long-term palliation can be achieved with aggressive surgery. The role of adjuvant chemotherapy and radiation therapy still needs to be evaluated. The aggressiveness of poorly differentiated and the mucin producing adenocarcinoma should temper radical surgical exercises.


Erythrocyte Li+/Na+ and Na+/H+ exchange, cardiac anatomy and function in insulin-dependent diabetics.
It has been proposed that an increased activity of cell membrane Na+/H+ exchange, mirrored by increased erythrocyte Li+/Na+ exchange, may facilitate cell hypertrophy and hyperplasia. Patients with insulin-dependent diabetes mellitus may develop a specific cardiomyopathy with systolic and diastolic abnormalities and increased thickness of the left ventricle. Therefore, we have investigated the relationships between erythrocyte Li+/Na+ and Na+/H+ exchange and echocardiographic parameters in 31 male insulin-dependent diabetics (aged 17-68), in good metabolic control. Three had untreated mild hypertension. In all patients the urinary albumin excretion rate was less than 200 micrograms min-1. Ten patients had a Li+/Na+ countertransport higher than 0.37 mmol l-1 cell h-1, the upper normal limit for our laboratory (0.49 +/- 0.10, mean +/- SD). In comparison with the patients with normal countertransport, they had increased interventricular septum thickness and relative wall thickness (h/r). End diastolic volume and cardiac index were reduced while blood pressure and urinary albumin excretion rate were similar. In the whole study group, interventricular septum thickness was significantly correlated to Li+/Na+ exchange (r = 0.61, P less than 0.001) and Na+/H+ exchange (r = 0.35, P less than 0.05), independently of the effect of age and blood pressure. Posterior wall thickness was correlated to Li+/Na+ exchange (r = 0.38, P less than 0.05) and h/r to Li+/Na+ exchange (r = 0.41, P less than 0.05) and to Na+/H+ exchange (r = 0.44, P less than 0.05). Li+/Na+ exchange was negatively correlated to cardiac index (r = -0.37, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Persistent suppression of contact hypersensitivity, and altered T-cell parameters in F344 rats exposed perinatally to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
The outcome of perinatal low-level TCDD exposure on the T-cell-mediated contact hypersensitivity (CHS) response in adult F344 rats was investigated. Suppression of the 2,4-dinitrofluorobenzene (DNFB)-specific contact hypersensitivity reponse occurred in mature offspring of dams dosed by gavage with 1microg or 3microg TCDD/kg on gestation day (GD) 14. To determine if this effect was correlated with altered distribution or activation of major T-cell subtypes, cells of the auricular lymph node draining the hapten-treated skin were evaluated by flow cytometry for expressed phenotype, including activation markers, 24h after challenge. Six-month-old female offspring with significantly decreased CHS and born to dams given 3microg TCDD/kg, had significantly greater proportion of CD4(+) T cells expressing a naive phenotype marker, CD45RC(hi), in their draining nodes. The greater relative frequency of this CD4(+) subset in peripheral lymphoid tissues associated with a reduced CHS in these rats may be attributed to a reduction in the proportion of CD4(+) T cells maintaining or recruited into an activated state. The CHS proved to be a valuable bioassay for investigating long-term immunotoxic effects of perinatal TCDD exposure in rats.


Long-term cadmium exposure impairs cognitive function by activating lnc-Gm10532/m6A/FIS1 axis-mediated mitochondrial fission and dysfunction.
Cadmium (Cd), a ubiquitous environmental contaminant, is deemed a possible aetiological cause of cognitive disorders in humans. Nevertheless, the exact mechanism by which chronic exposure to Cd causes neurotoxicity is not fully understood. In this study, mouse neuroblastoma cells (Neuro-2a cells) and primary hippocampal neurons were exposed to low-dose (1, 2, and 4 μM for Neuro-2a cells or 0.5, 1, and 1.5 μM for hippocampal neurons) cadmium chloride (CdCl2) for 72 h (h), and male mice (C57BL/6J, 8 weeks) were orally administered CdCl2 (0.6 mg/L, approximately equal to 2.58 μg/kg·bw/d) for 6 months to investigate the effects and mechanism of chronic Cd-induced neurotoxicity. Here, chronic exposure to Cd impaired mitochondrial function by promoting excess reactive oxygen species (ROS) production, altering mitochondrial membrane potential (Δψm) and reducing adenosine triphosphate (ATP) content, contributing to neuronal cell death. Specifically, microarray analysis revealed that the long noncoding RNA Gm10532 (lnc-Gm10532) was most highly expressed in Neuro-2a cells exposed to 4 μM CdCl2 for 72 h compared with controls, and inhibition of lnc-Gm10532 significantly antagonized CdCl2-induced mitochondrial dysfunction and neurotoxicity. Mechanistically, lnc-Gm10532 increased Fission 1 (FIS1) expression and mitochondrial fission by recruiting the m6A writer methyltransferase-like 14 (METTL14) and enhancing m6A modification of Fis1 mRNA. Moreover, lnc-Gm10532 was also required for chronic Cd-induced mitochondrial dysfunction and memory deficits in a rodent model. Therefore, data of this study reveal a new epigenetic mechanism of chronic Cd neurotoxicity.


The Maudsley rat strains as a probe to investigate noradrenergic-cholinergic interaction in cognitive function.
Central noradrenergic function in relation to cognitive performance was studied in the Maudsley rat strains. Neurochemical studies revealed a higher response to acute stress in the locus coeruleus (LC) in the Maudsley reactives (MR) than in the Maudsley non-reactives (MNRA). Autoradiographic studies showed that MNRAs had greater 125I clonidine binding to alpha 2 receptors in LC, which was accompanied by a higher behavioral sensitivity to clonidine. MRs had a deficit in working memory, but were superior to MNRAs in two reference memory tasks. MRs displayed a stronger preference for novel objects, with no strain differences in general exploratory activity. The behavioral profile of the MRs is similar to rats treated with drugs which enhance noradrenergic function. Furthermore, MNRA rats had greater availability of muscarinic receptors, which correlated with behavioral performance in the spatial working memory task. The differences in noradrenergic and cholinergic systems and their relationship to the behavioral profile make the Maudsley strains a useful tool to probe the interaction between two neurotransmitter systems in cognitive function.


An impact source localization technique for a nuclear power plant by using sensors of different types.
In a nuclear power plant, a loose part monitoring system (LPMS) provides information on the location and the mass of a loosened or detached metal impacted onto the inner surface of the primary pressure boundary. Typically, accelerometers are mounted on the surface of a reactor vessel to localize the impact location caused by the impact of metallic substances on the reactor system. However, in some cases, the number of accelerometers is not sufficient to estimate the impact location precisely. In such a case, one of useful methods is to utilize other types of sensor that can measure the vibration of the reactor structure. For example, acoustic emission (AE) sensors are installed on the reactor structure to detect leakage or cracks on the primary pressure boundary. However, accelerometers and AE sensors have a different frequency range. The frequency of interest of AE sensors is higher than that of accelerometers. In this paper, we propose a method of impact source localization by using both accelerometer signals and AE signals, simultaneously. The main concept of impact location estimation is based on the arrival time difference of the impact stress wave between different sensor locations. However, it is difficult to find the arrival time difference between sensors, because the primary frequency ranges of accelerometers and AE sensors are different. To overcome the problem, we used phase delays of an envelope of impact signals. This is because the impact signals from the accelerometer and the AE sensor are similar in the whole shape (envelope). To verify the proposed method, we have performed experiments for a reactor mock-up model and a real nuclear power plant. The experimental results demonstrate that we can enhance the reliability and precision of the impact source localization. Therefore, if the proposed method is applied to a nuclear power plant, we can obtain the effect of additional installed sensors.


Ontogeny of Tumor-associated Macrophages and Its Implication in Cancer Regulation.
Macrophages are innate immune cells with evolutionarily conserved functions in tissue maintenance and host defense. As such, macrophages are among the first hematopoietic cells that seed developing tissues, and respond to inflammatory insults by in situ proliferation or de novo differentiation from monocytes. Recent studies have revealed that monocyte-derived tumor-induced macrophages represent a major tumor-associated macrophage population, which can further expand following their differentiation in tumors. Compared to tissue-resident tumor-associated macrophages, these newly differentiated cells are phenotypically distinct, and likely play a unique role in tissue dysregulation and immune modulation in cancer. These findings imply that tumor growth elicits a specific innate immune response. In this review, we explore the different routes of macrophage seeding and maintenance in tissues during steady state and inflammation and how these principles underlie the responses observed during tumor development. In addition, we highlight the relationship between the origin and function of macrophages in different settings and how this knowledge may be used to create new opportunities for cancer immunotherapy.


Real-time molecular epidemiology of tuberculosis by direct genotyping of smear-positive clinical specimens.
We applied MIRU-VNTR (mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing) to directly analyze the bacilli present in 61 stain-positive specimens from tuberculosis patients. A complete MIRU type (24 loci) was obtained for all but one (no amplification in one locus) of the specimens (98.4%), and the allelic values fully correlated with those obtained from the corresponding cultures. Our study is the first to demonstrate that real-time genotyping of Mycobacterium tuberculosis can be achieved, fully transforming the way in which molecular epidemiology techniques can be integrated into control programs.


Role of long non coding RNA in plants under abiotic and biotic stresses.
Evolutionary processes have evolved plants to cope with several different natural stresses. Basic physiological activities of crop plants are significantly harmed by these stresses, reducing productivity and eventually leading to death. The recent advancements in high-throughput sequencing of transcriptome and expression profiling with NGS techniques lead to the innovation of various RNAs which do not code for proteins, more specifically long non-coding RNAs (lncRNAs), undergirding regulate growth, development, and the plant defence mechanism transcriptionally under stress situations. LncRNAs are a diverse set of RNAs that play key roles in various biological processes at the level of transcription, post-transcription, and epigenetics. These are thought to serve crucial functions in plant immunity and response to changes in the environment. In plants, however, just a few lncRNAs have been functionally identified. In this review, we will address recent advancements in comprehending lncRNA regulatory functions, focusing on the expanding involvement of lncRNAs in modulating environmental stress responsiveness in plants.


Understanding the immunological impact of the human mutation explosion.
The recent development of human exome sequencing technology has revealed that our immune system is riddled with more genetic defects than anyone imagined. As a legacy of the recent human population explosion, we each inherit hundreds of rare mutations that alter the sequence of proteins. This mutation load is ten times higher than that induced by experimental treatment of mice by ethylnitrosourea; a high fraction of which has substantial effects on immune function. This mutation burden is likely to be a major factor in the incidence of many human immune disorders, but understanding this at the level of individual patients will require new bioinformatics and experimental strategies to assess the impact of individual and combined mutations on immune response pathways.


Methionine5-enkephalin and opiate binding sites in the neurohypophysis of the bird, Gallus domesticus.
Uncertainties with respect to the cellular localization, binding characteristics and function of Met-enkephalin in the neurohypophysis of mammalian species prompted us to examine the neurohypophysis of a non-mammalian species for opioid material and opioid binding sites. In extracts of the neurohypophysis of the domestic fowl we found immunoassayable Met-enkephalin, but could not detect dynorphin(1-8)-like material. Met-enkephalin immunoreactivity was co-localized with mesotocin in the same nerve endings. Stereospecific opiate binding was specifically located in neurosecretosomes (isolated neurosecretory terminals) of the mesotocin type, as shown by autoradiography. Enkephalins therefore may modulate mesotocin release in an autocrine manner. The neurohypophysis of this common bird appears to be a favorable model for studies of enkephalin function in the absence of dynorphin.


Infectious salmon anemia virus (ISAV) replication is transiently inhibited by Atlantic salmon type I interferon in cell culture.
Infectious salmon anemia virus (ISAV) is a piscine orthomyxovirus, which causes multisystemic disease in farmed Atlantic salmon that may result in large losses. Previous work has suggested that ISAV is able to resist the antiviral state induced in cells by type I interferon (IFN). These studies were, however, mainly based on cytopathic effect (CPE) reduction assays. Here we have investigated the antiviral activity of Atlantic salmon IFNa1, IFNb and IFNc against ISAV using quantitative PCR (qPCR) of segment 6, Western blot analysis of ISAV proteins and viral yield reduction assays, in addition to CPE reduction assays. Antiviral effects of IFNs were tested against the high virulent strain ISAV4 and the low virulent strain ISAV7 both at the optimum growth temperature 15°C and at 20°C. As expected, IFNa1 showed little protection against CPE development in cells after infection with both strains at 15°C. However, the qPCR and Western blot analysis clearly showed strong inhibition of replication of the virus strains by IFNa1 between 24 and 72h after infection. The inhibitory effect declined four to five days post-infection, which explains the low protection against CPE development 7-10 days later. At 20°C, IFNa1 showed strong protection against CPE development, probably due to slower virus growth. IFNc showed similar antiviral activity as IFNa1 against ISAV4 while IFNb showed lower activity. There were observed differences between ISAV4 and ISAV7 both with respect inhibition by IFNa1 and ability to induce the two IFN-inducible antiviral effector proteins, Mx and ISG15, which may be related to differences in virulence properties and/or adaption to growth in cell culture.


Cardiovascular effects of microinjection of adenosine into the nucleus tractus solitarius.
Rats were anesthetized with urethane and limited occipital craniotomy was conducted to expose the caudal medulla in the region of the obex. Microinjections of adenosine were made into the nucleus tractus solitarius and heart rate and blood pressure responses recorded. Adenosine produced dose-related decreases in blood pressure and heart rate. The data indicate that adenosine may play a neuromodulatory role in central cardiovascular control areas.


The Limits of Three-Dimensionality: Systematic Assessment of Effective Anode Macrostructure Dimensions for Mixed-Culture Electroactive Biofilms.
This study analyzes the biofilm growth and long-term current production of mixed-culture, electrochemically active biofilms (EABs) on macrostructured electrodes under low-shear-force conditions. The channel dimensions were altered systematically in the range 400 μm to 2 mm, and the channel heights were varied between 1 and 4 mm to simulate macrostructures of different scales. Electrodes with finer-structured surfaces produced higher current densities in the short term owing to their large surface area but were outperformed in the long term because the accumulation of biomass led to limitations of mass transfer into the structures. The best long-term performance was observed for electrodes with channel dimensions of 1×4 mm, which showed no significant decrease in performance in the long term. Channels with a diameter of 400 μm were overgrown by the biofilm, which led to a transition from 3 D to 2 D behavior, indicating that structures of this scale might not be suitable for long-term operation under low-shear-stress conditions.


Endosomes differ from plasma membranes in the phospholipid molecular species composition.
125I-Labeled epidermal growth factor was incorporated into and highly concentrated in endosomes of Chinese hamster V79-UF cells during incubation at 37 degrees C for 8 min after binding to its receptors on the cell surface at 4 degrees C. From the labeled cells, endosomes were isolated by isopycnic centrifugation on a Percoll density gradient and then sucrose density gradients. The isolated endosomes were mostly free from contamination by Golgi, endoplasmic reticulum, lysosome, plasma membrane and mitochondria. Endosome membranes were found to differ from plasma membranes in the phospholipid composition. Sphingomyelin and phosphatidylserine were enriched in endosomes, compared with plasma membranes. Diacylphosphatidylcholine and diacylphosphatidylethanolamine were major phospholipids of the membranes in both organelles. The contents of molecular species of diacylphosphatidylcholine and diacylphosphatidylethanolamine with two monoenoic fatty acids were lower in endosomes than in plasma membranes. The differences in the polar head group and molecular species compositions of phospholipids between endosomes and plasma membranes did not change, regardless of whether or not the proportions of phospholipid molecular species in plasma membranes changed. The significance of the lipids in endosomes is discussed.


Experimental pneumococcal meningitis in rabbits: the increase of matrix metalloproteinase-9 in cerebrospinal fluid correlates with leucocyte invasion.
Gelatinolytic activity of matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-2, was studied by quantitative zymography in a rabbit model of bacterial meningitis during 24 h after inoculation with Streptococcus pneumoniae. In cerebrospinal fluid (CSF), MMP-2 was constitutively present and its level did not change during the experiment. In contrast, MMP-9, hardly detectable in CSF of healthy animals, increased dramatically. The increase of MMP-9 was correlated with both, an increase of CSF cell count and of total protein concentration. Intrathecal production of MMP-9 and MMP-2 was demonstrated by zymography of equal amounts of total protein from CSF and serum. Homogenates, prepared from various cortical regions of infected rabbits did not show increase of MMP activities. On the other hand, leucocytes isolated from CSF expressed high levels of MMP-9 suggesting a significant contribution of these cells to the elevation of MMP-9 activity in this body fluid.


Genome scale engineering techniques for metabolic engineering.
Metabolic engineering has expanded from a focus on designs requiring a small number of genetic modifications to increasingly complex designs driven by advances in genome-scale engineering technologies. Metabolic engineering has been generally defined by the use of iterative cycles of rational genome modifications, strain analysis and characterization, and a synthesis step that fuels additional hypothesis generation. This cycle mirrors the Design-Build-Test-Learn cycle followed throughout various engineering fields that has recently become a defining aspect of synthetic biology. This review will attempt to summarize recent genome-scale design, build, test, and learn technologies and relate their use to a range of metabolic engineering applications.


Anorectal incontinence: diagnosis and treatment.
In correcting anorectal incontinence, the analysis of all known factors responsible for a lack of function is mandatory. Besides anamnestic and clinical data, manometric investigation is especially helpful. Continence may be improved by conservative measures (biofeedback training, muscle training, and drugs). The indication for surgical procedures depends on clinical and manometric findings: missed portions of the sphincteric muscle complex are reintegrated with a repull-through procedure. In some cases, Kottmeier's levatorplasty or a modification of it has led to some improvement of continence. Whenever a call to stool was present, gracilis transposition has markedly improved anorectal function in 22 of 27 operated patients. Free transplantation of palmaris longus muscle has not proven to be of functional advantage. Doubling the circular colonic musculature and an S-shaped anoplasty at the time of the primary pull-through procedure may lead to continence in the future.


Effectiveness and Safety of Rivaroxaban and Low Molecular Weight Heparin in Cancer-Associated Venous Thromboembolism.
Direct-acting oral anticoagulants (DOACs) are alternatives to low molecular weight heparin (LMWH) in most cancer-associated thrombosis (CAT) patients. This study sought to compare the effectiveness and safety of rivaroxaban and LMWH for venous thromboembolism (VTE) treatment in patients with an active cancer type not associated with a high risk of DOAC bleeding. An analysis of electronic health records from January 2012 to December 2020 was performed. Patients were adults, had active cancer, experienced an index CAT event, and were treated with rivaroxaban or LMWH. Patients with cancers with an established high risk of bleeding on DOACs were excluded. Baseline covariates were balanced using propensity score-overlap weighting. HRs with 95% CIs were calculated. We identified 3,708 CAT patients treated with rivaroxaban (29.5%) or LMWH (70.5%). The median (25th-75th percentiles) time on anticoagulation was 180 (69-365) and 96 (40-336) days for rivaroxaban and LMWH patients. At 3 months, rivaroxaban was associated with a 31% reduced risk of recurrent VTE vs LMWH (4.2% vs 6.1%; HR: 0.69; 95% CI: 0.51-0.92). No difference in bleeding-related hospitalizations or all-cause mortality was observed (HR: 0.79; 95% CI: 0.55-1.13 and HR: 1.07; 95% CI: 0.85-1.35, respectively). Rivaroxaban reduced the recurrent VTE risk (HR: 0.74; 95% CI: 0.57-0.97) but not bleeding-related hospitalizations or all-cause mortality at 6 months. At 12 months, no difference was observed between cohorts for any of the previously mentioned outcomes. Among active cancer patients experiencing VTE and not at high risk of bleeding on DOACs, rivaroxaban was associated with a reduced risk of recurrent VTE versus LMWHs at 3 and 6 months but not 12 months. (Observational Study in Cancer-Associated Thrombosis for Rivaroxaban-United States Cohort [OSCAR-US]; NCT04979780).


Correction for Diaz, Paragonimiasis Acquired in the United States: Native and Nonnative Species.
Volume 26, no. 3, p. 493–504, 2013. Page 497: The snail shown in Fig. 8 is not a slender walker snail (Pomatiopsis lapidaria), as indicated in the legend of the figure, but rather a sharp hornsnail (Pleurocera acuta). The correct image (that of the slender walker snail, Pomatiopsis lapidaria; courtesy of Steve Cringan, photographer) is shown below.


A bacteriological study of otitis media with effusion. Concurrent coagulase-negative staphylococcal infections in the middle ear.
We investigated the bacteriology of 50 chronic middle ear effusions from 30 children (mean age, 5 years 4 months) and compared this with the microorganisms present in the external ear canals and adenoids of each patient to distinguish pure middle ear bacteria from probable contaminations. Coagulase-negative staphylococci (CS), formerly considered to be non-pathogens, were the most frequently isolated bacteria in the middle ear effusions and were followed in incidence by alpha-hemolytic streptococci and group D streptococci. CS were found in 24% of all effusions and in 44% of the infected effusions. Most of the CS strains belonged to the species of Staphylococcus epidermidis. Although the majority of CS isolated from the middle ear effusions studied proved not to be contaminants, the populations of CS in the middle ear and external ear canal showed similar biochemical reaction patterns, antimicrobial susceptibilities, and in vitro production of mucus. No correlation was found between the bacteria present in adenoidal tissue and middle ear effusions.


Hysterectomy in the United States, 1988-1990.
To describe patient characteristics and diagnoses associated with hysterectomy in the United States from 1988-1990 using data from the National Hospital Discharge Survey. We analyzed data from the National Hospital Discharge Survey, an annual probability sample of discharges from nonfederal, short-stay hospitals in the United States. A population-based sample of all women aged 15 years or older in the United States civilian population who had a hysterectomy during 1988-1990 was examined to characterize factors associated with hysterectomy: patients' age and race, diagnoses, surgical approach, and oophorectomy. Approximately 1.7 million women had a hysterectomy during 1988-1990. The highest rates--100.5 hysterectomies per 10,000 women--were for women aged 30-54 years. Total rates of hysterectomy for black women were similar to those for white women (61.7 and 56.5 per 10,000 women, respectively); uterine leiomyoma ("fibroid tumor") was reported as the primary diagnosis for 61% of black women and 29% of white women. Abdominal surgery was used for 75% of all hysterectomies. Concomitant bilateral oophorectomy was done for 37% of the women under 45 years old and 68% of the women 45 years or older. Two-thirds of all hysterectomies for noncancerous conditions were performed for uterine leiomyoma or endometriosis--conditions that are most common before the age of menopause. Future assessments of the appropriateness of hysterectomy will require better understanding of these disorders. Continued monitoring of hysterectomy rates is critical to understanding the appropriate use of hysterectomy, alternative therapies for uterine disorders, and future trends in women's health care.


Allopurinol ameliorates thioacetamide-induced acute liver failure by regulating cellular redox-sensitive transcription factors in rats.
Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-қB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.


Erratum: changes in the prevalence of childhood asthma in seoul from 1995 to 2008 and its risk factors.
[This corrects the article on p. 27 in vol. 3, PMID: 21217922.].


Mindfulness or meditation therapy for Parkinson's disease: A systematic review and meta-analysis of randomized controlled trials.
Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Mindfulness and meditation therapies have been demonstrated as effective alternative treatments for patients with neurological disorders. However, the effects of mindfulness and meditation therapies on PD remain unclear. This meta-analysis investigated the effects of mindfulness and meditation therapies in PD patients. A literature search was conducted using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials comparing mindfulness and meditation therapies with control treatments in patients with PD. Nine articles involving eight trials were included, with a total of 337 patients. Our meta-analysis revealed that mindfulness and meditation therapies significantly improved Unified Parkinson's Disease Rating Scale-Part III score (mean difference [MD] = -6.31, 95% confidence interval [95% CI] = -8.57 to -4.05) and cognitive function (standard mean difference [SMD] = 0.62, 95% CI = 0.23 to 1.02). However, no significant differences were discovered between mindfulness therapies and control in gait velocity (MD = 0.05, 95% CI = -0.23 to 0.34), Parkinson's Disease Questionnaire-39 Summary Index (MD = 0.51, 95% CI = -1.12 to 2.14), activities of daily living (SMD = -1.65, 95% CI = -3.74 to 0.45), depression (SMD = -0.43, 95% CI = -0.97 to 0.11), anxiety (SMD = -0.80, 95% CI = -1.78 to 0.19), pain (SMD = 0.79, 95% CI = -1.06 to 2.63), or sleep disturbance (SMD = -0.67, 95% CI = -1.58 to 0.24). Mindfulness and meditation therapies may serve as complementary and alternative treatments for PD patients.


Extracellular vesicles from BALF of pediatric cystic fibrosis and asthma patients increase epithelial sodium channel activity in small airway epithelial cells.
Extracellular Vesicles (EVs) are nanosized vesicles derived from all cell types. EV cargo allows for intercellular communication, intracellular signaling, and regulation of proteins in recipient cells. We tested the hypothesis that EVs isolated from the bronchoalveolar-lavage fluid (BALF) of pediatric cystic fibrosis (CF) or pediatric asthma patients increase epithelial sodium channel (ENaC) activity in normal human small airway epithelial cells (SAECs) and the mechanism involves specific EV lipids. We characterized EVs from BALF of pediatric CF and pediatric asthma patients by nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. The CF and asthma pediatric groups were similar in BALF electrolytes concentration and cell count, except for neutrophils, which were higher in the CF group. Lipidomic analyses for each group of EVs were performed using targeted mass spectrometry. Phosphatidylethanolamine, sphingomyelins, and triacylglycerol were enriched in both groups, but phosphatidylcholine and phosphatidylinositol concentrations were greater in the CF group compared to the asthma group, and the opposite trend was found for phosphatidylserine. Endogenous ENaC activity, measured by the single-channel patch-clamp technique, increased in normal human SAECs after challenging SAEC with EVs from either the CF or asthma groups compared to control EVs. In conclusion, EVs isolated from BALF of pediatric patients with CF or asthma have unique lipid profiles. Despite the differences, both types of EVs increase ENaC activity in normal human SAECs compared to control EVs isolated from the conditioned media of these cells.


Classroom aeroallergen exposure in Arkansas head start centers.
The impact of preschool environmental conditions on classroom aeroallergen concentrations is not fully understood. To examine the relationship between school environmental conditions and classroom aeroallergen concentrations in the Pulaski County Head Start (HS) Program. Thirty-three HS centers in Pulaski County, Arkansas, underwent a detailed environmental evaluation. Classroom settled dust samples were analyzed for the presence of common indoor allergens. Classroom eating (70%), wall-to-wall carpeting (58%), and water damage (33%) were common. Median classroom allergen levels were as follows: dust mite (Der p 1 and Der f 1), 0.6 microg/g; Fel d 1, 0.4 microg/g; Can f 1, 1.7 microg/g; cockroach, below detection; Mus m 1, 0.18 microg/g; and mold spores, 17,800 CFU/g. Can f 1 and Mus m 1 allergens were detected in 100% of HS centers. Facilities with carpeting, increased humidity, and single-use facilities showed trends toward increased dust mite concentrations. Detectable cockroach allergen was more common in classrooms cleaned by teachers than by professional housekeepers. Aeroallergens were commonly detected in Pulaski County HS center classrooms, with dog and mouse allergens detected in 100% of centers. Median classroom allergen concentrations were low, and classroom characteristics were not strongly predictive of increased allergen exposure.


Cardiac energetics: sense and nonsense.
1. The background to current ideas in cardiac energetics is outlined and, in the genomic era, the need is stressed for detailed knowledge of mouse heart mechanics and energetics. 2. The mouse heart is clearly different to the rat in terms of its excitation-contraction (EC) coupling and the common assumption that heart rate difference between mice and humans will account for the eightfold difference in myocardial oxygen consumption is wrong, because the energy per beat of the mouse heart is approximately one-third that of the human heart. 3. In vivo evidence suggests that there may well be an eightfold species difference in the non-beating metabolism of mice and human hearts. It is speculated that the magnitude of basal metabolism in the heart is regulatable and that, in the absence of perfusion, it falls to approximately one-quarter of its in vivo rate and that in clinical conditions, such as hibernation, it probably decreases; its magnitude may be controlled by the endothelium. 4. The active energy balance sheet is briefly discussed and it is suggested that the activation heat accounts for 20-25% of the active energy per beat and cross-bridge turnover accounts for the balance. It is argued that force, not shortening, is the major determinant of cardiac energy usage. 5. The outcome of recent cardiac modelling with variants of the Huxley and Hill/Eisenberg models is described. It has been necessary to invoke 'loose coupling' to replicate the low cardiac energy flux measured at low afterloads (medium to high velocities of shortening). 6. Lastly, some of the unexplained or 'nonsense' energetic data are outlined and eight unsolved problems in cardiac energetics are discussed.


T cell cytokine responses to stimulation with Ureaplasma parvum in pregnancy.
Ureaplasma spp. are a common vaginal microorganism causally linked to inflammation-driven preterm birth (PTB). The nature of the immune response to Ureaplasma spp. may influence PTB risk. This study sought to define maternal T cell cytokine responses to in vitro stimulation with Ureaplasma parvum serovar 3 (UpSV3) in vaginally colonised (UP+) and non-colonised (UP-) pregnant women. Whole blood flow cytometry demonstrated an increase (p=0.027) in the baseline frequency of IFNγ-positive CD3(+)CD4(-)(CD8(+)) T cells in UP+ women. UpSV3 stimulation resulted in a significant and specific increase (p=0.001) in the frequency of IFNγ-positive CD3(+)CD4(-)(CD8(+)) T cells, regardless of vaginal colonisation status. UpSV3 stimulation also increased the frequency of IFNγ-positive CD3(+)CD4(+) T cells, particularly in the UP+ group (p=0.003). This is the first published study to examine T cell responses to Ureaplasma spp. Future appropriately-powered studies are needed to assess whether insufficient priming or a loss of tolerance to Ureaplasma spp. is occurring in UP+ women at risk of PTB.


Brain activity across the development of automatic categorization: a comparison of categorization tasks using multi-voxel pattern analysis.
Previous evidence suggests that relatively separate neural networks underlie initial learning of rule-based and information-integration categorization tasks. With the development of automaticity, categorization behavior in both tasks becomes increasingly similar and exclusively related to activity in cortical regions. The present study uses multi-voxel pattern analysis to directly compare the development of automaticity in different categorization tasks. Each of the three groups of participants received extensive training in a different categorization task: either an information-integration task, or one of two rule-based tasks. Four training sessions were performed inside an MRI scanner. Three different analyses were performed on the imaging data from a number of regions of interest (ROIs). The common patterns analysis had the goal of revealing ROIs with similar patterns of activation across tasks. The unique patterns analysis had the goal of revealing ROIs with dissimilar patterns of activation across tasks. The representational similarity analysis aimed at exploring (1) the similarity of category representations across ROIs and (2) how those patterns of similarities compared across tasks. The results showed that common patterns of activation were present in motor areas and basal ganglia early in training, but only in the former later on. Unique patterns were found in a variety of cortical and subcortical areas early in training, but they were dramatically reduced with training. Finally, patterns of representational similarity between brain regions became increasingly similar across tasks with the development of automaticity.


Influence of dietary fiber intake and soluble to insoluble fiber ratio on reproductive performance of sows during late gestation under hot climatic conditions.
This study evaluated dietary fiber (DF) level and the ratio of soluble fiber (SF): insoluble fiber (ISF) impact on sows' reproductive performance under heat stress. Forty sows at day 90 of gestation were assigned to four treatments. HH diet had, 20% DF, 1:4, SF:ISF ratio; HL, 20% DF, 1:6, SF:ISF ratio; LH, 14% DF, 1:4, SF:ISF, LL, 14% DF, 1:6, SF:ISF. Results showed that; lactation back-fat loss was lower (P < 0.05) in HH . Feed intake was higher (P < 0.05) in HH and HL. Farrowing duration shorter (P < 0.05) in HH. Constipation index was higher (P < 0.05) in HH and LH. Weaning piglets' body weight was greater (P < 0.05) in HH than LH and LL. Hair cortisol was lower (P < 0.05) in HH than HL, and LL. Acetate, propionate, isovalerate, and butyrate was higher (P < 0.05) in HH and LH. Plasma zonulin, fecal lipocalin-2 were lower (P < 0.05) in HH, and HL. Superoxide dismutase tended to be higher (P = 0.056) and malondialdehyde tended to be lower (P = 0.069) in HH and HL. We opined that higher levels of dietary fiber and soluble fiber could ameliorate heat stress in gestating sows.


[The magnitude of forces acting on the proximal femur in various weight alleviating gait forms with reduced ground reaction forces].
To estimate the forces of the hip during partial or non-body-weight-bearing-gait a simple mechanical principle was used. For identification of the acting muscles of the hip during the swing period Electromyography was used. In the pure swing period without ground touch, being recommended as "de-loading" for the hip, forces resulted up to 85% of body-weight. In contrast to that, partial body-weight-bearing with limb-weight (approximately 12-15% body weight) resulted in the most efficient reduction of hip forces.


Polymeric alkenoxy amino acid surfactants: II. Chiral separations of beta-blockers with multiple stereogenic centers.
Two amino acid-based (leucine and isoleucine) alkenoxy micelle polymers were employed in this study for the separation of multichiral center-bearing beta-blockers, nadolol and labetalol. These polymers include polysodium N-undecenoxy carbonyl-L-leucinate (poly-L-SUCL) and polysodium N-undecenoxy carbonyl-L-isoleucinate (poly-L-SUCIL). Detailed synthesis and characterization were reported in our previous paper [26]. It was found that poly-L-SUCIL gives better chiral separation than poly-L-SUCL for both nadolol and labetalol isomers. The use of 50-100 mM poly-L-SUCIL as a single chiral selector provided separation of four and three isomers of labetalol and nadolol, respectively. Further optimization in separation of both enantiomeric pairs of nadolol and labetalol was achieved by evaluation of type and concentration of organic solvents, capillary temperature as well type and concentration of cyclodextrins. A synergistic approach, using a combination of poly-L-SUCIL and sulfated beta-CD (S-beta-CD) was evaluated and it showed dramatic separation for enantiomeric pairs of nadolol. On the other hand for labetalol enantiomers, separation was slightly decreased or remain unaffected using the dual chiral selector system. Finally, simultaneous separation of both nadolol and labetalol enantiomers was achieved in a single run using 25 mM poly-L-SUCIL and 5% w/v of S-beta-CD in less then 35 min highlighting the importance of high-throughput chiral analysis.


Microarray analysis of cultured human brain aggregates following cortisol exposure: implications for cellular functions relevant to mood disorders.
Increased cortisol levels in humans are often observed in patients suffering from mood disorders. In this study human fetal brain aggregates were exposed to cortisol at 500 nM for 3 weeks, as an in-vitro model of chronic cortisol exposure. Microarray analysis on extracted mRNA using the Affymetrix U133A platform was then performed. Our results demonstrated a significant effect of cortisol on 1648 transcripts; 736 up-regulated and 912 down-regulated genes. The most differentially regulated biological categories were: RNA processing, protein metabolism, and cell growth. Within these categories we observed a down-regulation of fibroblast growth factor 2 (FGF2) (-1.5-fold) and aquaporin4 (AQP4) (-1.7-fold), alongside an up-regulation of fibroblast growth factor 9 (FGF9) (+1.7-fold) and vesicle associated membrane protein2 (VAMP2) (+1.7-fold). FGF2, FGF9, AQP4 and VAMP2 changes were confirmed at the protein level by immunohistochemistry. Alterations in FGF transcripts are in keeping with recent literature demonstrating such effects in patients with mood disorders.


Design, syntheses, and anti-tuberculosis activities of conjugates of piperazino-1,3-benzothiazin-4-ones (pBTZs) with 2,7-dimethylimidazo [1,2-a]pyridine-3-carboxylic acids and 7-phenylacetyl cephalosporins.
Tuberculosis (TB) remains one of the most threatening diseases in the world and the need for development of new therapies is dire. Herein we describe the rationale for the design and subsequent syntheses and studies of conjugates between pBTZ and both the imidazopyridine and cephalosporin scaffolds. Overall some compounds exhibited notable anti-TB activity in the range of 2-0.2 μM in the Microplate Alamar Blue (MABA) Assay.


Low-frequency sonophoresis: current status and future prospects.
Application of ultrasound enhances skin permeability to drugs, a phenomenon referred to as sonophoresis. Significant strides have been made in sonophoresis research in recent years, especially under low-frequency conditions (20 kHz<f<100 kHz). This article reviews the mechanistic principles and current status of sonophoresis under low-frequency conditions. Several therapeutic macromolecules including insulin, low-molecular weight heparin, and vaccines have been delivered using low-frequency sonophoresis in vivo. Clinical trials have been performed with several drugs including lidocaine and cyclosporin. Novel theoretical and experimental approaches have provided insights into the mechanisms of low-frequency sonophoresis. Current understanding of these mechanisms is presented.


Beyond freedom and dignity at 40: comments on behavioral science, the future, and chance (2007).
Forty years after the publication of Beyond Freedom and Dignity (Skinner, 1971) and the continuing growth of behavior analysis, the future of humanity and the role of behavioral science in that future remain uncertain. A recent paper by Chance (2007) documented a shift in Skinner's views during the last years of his life. Skinner had long advocated a science and technology of behavior for finding and engineering solutions to cultural and global problems and advancing human development. This optimism had given way under a gradual realization that the science of behavior was in fact showing how such problems were unlikely to be solved in time to avert a variety of possible disasters. Chance described nine behavioral phenomena that appear to interfere with effective problem-solving behavior on a large scale and in effective time frames. These phenomena are reviewed toward an analysis of common themes. Research is also reviewed that involves nonverbal, verbal, and cultural contingencies that may lead to applications designed to address the common themes. Problems and strategies of implementation are also discussed. The challenges are daunting, but may nevertheless be regarded as technical problems best suited for a science and technology of behavior.


Role of toll-like receptor 4 in diabetic retinopathy.
Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus (DM) and a leading cause of blindness worldwide. Evidence has shown that DR is an inflammatory disease with hyperglycemia playing a causative role in the development of its main features, including inflammation, cellular apoptosis, neurodegeneration, oxidative stress, and neovascularization. Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors (PRRs) responsible for the initiation of inflammatory and immune responses. TLR4 identifies both endogenous and exogenous ligands and is associated with various physiological and pathological pathways in the body. While the detailed pathophysiology of DR is still unclear, increasing data suggests a crucial role for TLR4 in the development of DR. Due to hyperglycemia, TLR4 expression increases in diabetic retina, which activates various pathways leading to DR. Considering the role of TLR4 in DR, several studies have focused on the association of TLR4 polymorphisms and risk of DR development. Moreover, evidence concerning the effect of microRNAs in the pathogenesis of DR, through their interaction with TLR4, indicates the determinant role of TLR4 in this disease. Of note, several agents have proven as effective in alleviating DR through the inhibition of the TLR4 pathway, suggesting new avenues in DR treatment. In this review, we provided a brief overview of the TLR4 structure and biological function and a more comprehensive discussion about the mechanisms of TLR4 activation in DR. Furthermore, we summarized the relationship between TLR4 polymorphisms and risk of DR and the relationship between microRNAs and TLR4 in DR. Finally, we discussed the current progress in designing TLR4 inhibitors, which could be helpful in DR clinical management.


Adjunctive use of locally delivered host-modulators in intra-bony defects as part of step 2 periodontal therapy: systematic review, meta-analysis and trial sequential analysis.
This systematic review and meta-analysis aimed at investigate the role of locally delivered host-modulators in combination with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level and reducing bone defect depth in intra-bony defects. RCT with at least 6 months follow-up were included in this study. Risk of bias assessment was performed with Cochrane collaboration tool and Grade GRADEpro. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence. 22 studies met the inclusion criteria and were included in this systematic review. At 6 months locally delivered host-modulators significantly improved PD and CAL and bone defect depth. Considering the emerging role of host-inflammatory response in the treatment of periodontitis, several studies are exploring the role of locally delivered host modulators as an adjunct to step 2 of periodontal therapy.


Physical Frailty Phenotype and the Development of Geriatric Syndromes in Older Adults with Coronary Heart Disease.
Frailty, a clinical state of vulnerability, is associated with subsequent adverse geriatric syndromes in the general population. We examined the long-term impact of frailty on geriatric outcomes among older patients with coronary heart disease. We used the National Health and Aging Trends Study, a prospective cohort study linked to a Medicare sample. Coronary heart disease was identified by self-report or International Classification of Diseases (ICD) codes 1-year prior to the baseline visit. Frailty was measured using the Fried physical frailty phenotype. Geriatric outcomes were assessed annually during a 6-year follow-up. Of the 4656 participants, 1213 (26%) had a history of coronary heart disease 1-year prior to their baseline visit. Compared to those without frailty, subjects with frailty were older (ages ≥75: 80.9% vs 68.9%, P < 0.001), more likely to be female, and belong to an ethnic minority. The prevalence of hypertension, stroke, falls, disability, anxiety/depression, and multimorbidity were much higher in the frail, than nonfrail, participants. In a discrete time survival model, the incidence of geriatric syndromes during 6-year follow-up including 1) dementia, 2) loss of independence, 3) activities of daily living disability, 4) instrumental activities of daily living disability, and 5) mobility disability were significantly higher in the frail than in the nonfrail older patients with coronary heart disease. In patients with coronary heart disease, frailty is a risk factor for the accelerated development of geriatric outcomes. Efforts to identify frailty in the context of coronary heart disease are needed, as well as interventions to limit or reverse frailty status for older patients with coronary heart disease.


Prenatal exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may influence birth weight among infants in a Swedish cohort with background exposure: a cross-sectional study.
Prenatal exposure to persistent organic pollutants, e.g. polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) has been suggested to negatively affect birth weight although epidemiological evidence is still inconclusive. We investigated if prenatal exposure to PCBs and PBDEs is related to birth weight in a Swedish population with background exposure. Breast milk was sampled during the third week after delivery from first-time mothers in Uppsala county, Sweden 1996-2010 (POPUP cohort) (N = 413). Samples were analysed for di-ortho PCBs (CB-138, 153, 180) and tetra- to hexa- brominated PBDEs (BDE-47, 99, 100, 153). Simple and multiple linear regression models were used to investigate associations between lipid-adjusted, ln-transformed PCB and PBDE concentrations, and birth weight. Covariates included in the multivariate regression model were PCB and PBDE exposure, maternal age, pre-pregnancy BMI, weight gain during pregnancy, education, smoking, gender of the infant and gestational length. The effect of including fish consumption was also investigated. In the multivariate model, prenatal exposure to di-ortho PCBs was significantly associated with increased birth weight (β = 137; p = 0.02). The result did not change when gestational length was added to the model. An inverse association between PBDE(4) (sum of BDE-47, -99, -100 and -153) and birth weight was observed in the multivariate model including gestational length (β = -106; p = 0.04). Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders of the association between di-ortho PCBs and birth weight. The associations were not alleviated after adjustment for fish consumption, a major source of PCB and PBDE exposure. The observed associations were stronger for boys than for girls. Our results indicate that prenatal exposure to di-ortho PCBs and PBDE(4) may influence birth weight in different directions, i.e. PCB exposure was associated with higher birth weight and PBDE exposure with lower birth weight. Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders that may hide positive association between di-ortho PCB exposure and birth weight if they are not included in the statistical model. We speculate that even small PCB- and PBDE-induced shifts in the distribution of birth weight may influence future public health in populations with background exposure.


Using post-bronchodilator FEV₁ is better than pre-bronchodilator FEV₁ in evaluation of COPD severity.
The current standards for the diagnosis and treatment of patients with COPD clearly rely on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria based on post-bronchodilator spirometric values. However, clinical evidence for using the post-bronchodilator FEV₁ in the severity classification has not been fully investigated. Patients with COPD were enrolled and followed up prospectively between October 2006 and January 2011. We compared the observed 3-year risk of all causes and respiratory mortality with the risk predicted by the pre- and post-bronchodilator percent predicted FEV₁. Other important phenotypes including BMI, MMRC dyspnea scale, ECOG performance status and severe AECOPD (acute exacerbation) were also compared between the two groups. The different severity classifications of COPD, measured according the GOLD guidelines by post- and pre-bronchodilator percent predicted FEV₁ were compared for prediction of mortality. There were 35 deaths among the 300 COPD patients (11.7%). Multivariate analysis showed that the post-bronchodilator percent predicted FEV₁ was a significant independent predictor of mortality but pre-bronchodilator percent predicted FEV₁ was not (p = 0.008 vs 0.126) and it was more strongly correlated with all studied predictors of outcome than the pre-bronchodilator percent predicted FEV₁. Kaplan-Meier analysis showed that the discrimination ability to predict mortality from the GOLD criteria using post bronchodilator percent predicted FEV₁ (p = 0.009) was better than using pre-bronchodilator percent predicted FEV₁ (p = 0.131). The post-bronchodilator percent predicted FEV1 is better than the pre-bronchodilator percent predicted FEV₁ in the evaluation of the severity of disease in COPD patients and is more accurate in predicting the risk of death by the GOLD classification.


Pilot study of combination chemotherapy of S-1, a novel oral DPD inhibitor, and interferon-alpha for advanced hepatocellular carcinoma with extrahepatic metastasis.
To the authors' knowledge, there is no effective therapy for extrahepatic metastasis of hepatocellular carcinoma (HCC). In a pilot study, the results of combination therapy of S-1, a novel oral dehydropyrimidine dehydrogenase (DPD) inhibitor, and interferon-alpha (IFN-alpha) are reported for HCC patients with extrahepatic metastasis. Twelve patients with extrahepatic metastasis of HCC were enrolled in the pilot study. S-1 was administered orally at a dose based on body surface area, twice daily after a meal, for 4 weeks. IFN-alpha was injected subcutaneously on Days 1, 3, and 5 of each week. One course consisted of consecutive administration for 28 days followed by 14 days rest. An objective response was observed in 3 (25%) of 12 patients. The overall 1-year survival rate was 61.7%. Grade 3 leukocytopenia was observed in 1 patient (8.3%). No severe toxicity or treatment-related deaths were observed. The combination therapy of S-1 and IFN-alpha appears to be highly efficacious, with low toxicity in patients with extrahepatic metastases of HCC. The combination chemotherapy of oral S-1 and subcutaneous IFN-alpha is a potentially promising treatment strategy for advanced HCC with extrahepatic metastasis.


Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature.
Pulmonary megakaryocytes participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD). In this autopsy study, we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute lung injury (7.61 ± 5.59 megakaryocytes per 25 high-power fields vs. 1.14 ± 0.86 for the control group, p < 0.05). We analyzed samples of 18 patients, most of whom died after prolonged disease and use of mechanical ventilation. Most patients showed advanced DAD and abnormal coagulation parameters with high levels of fibrinogen, D-dimers, and variable thrombocytopenia. For comparison, pulmonary samples from a group of 14 non-COVID-19 patients dying with DAD were reviewed. They showed similar pulmonary histopathologic findings and an increase in the number of megakaryocytes (4 ± 4.17 vs. 1.14 ± 0.86 for the control group, p < 0.05). Megakaryocyte count in the COVID-19 group was greater but did not reach statistical significance (7.61 ± 5.59 vs. 4 ± 4.17, p = 0.063). Regardless of the cause, pulmonary megakaryocytes are increased in patients with DAD. Their high number seen in COVID-19 patients suggests a relation with the thrombotic events so often seen these patients. Since the lung is considered an active site of megakaryopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response.


Attenuation of Babesia bovis by in vitro cultivation.
A virulent strain of Babesia bovis was adapted to grow in erythrocyte culture in the presence of equine serum and in lieu of bovine serum. Four splenectomized calves inoculated with the adapted strain, 429, developed hematologic signs of infection and a low grade fever, but remained free of central nervous system (CNS) signs and recovered. All of six control animals inoculated with a virulent strain reacted severely and five showed CNS signs and died. The calves injected with the attenuated strain were solidly immune when challenged with the virulent strain at 44 or 78 days after vaccination.


RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region.
Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization of a set of aptamers targeting the cis-acting replication element (CRE) of the HCV genome, an essential partner for viral replication and also involved in the regulation of protein synthesis. Forty-four aptamers were tested for their ability to interfere with viral RNA synthesis in a subgenomic replicon system. Some of the most efficient inhibitors were further evaluated for their potential to affect the recruitment of the HCV RNA-dependent RNA polymerase (NS5B) and the viral translation in cell culture. Four aptamers emerged as potent inhibitors of HCV replication by direct interaction with functional RNA domains of the CRE, yielding a decrease in the HCV RNA levels higher than 90%. Concomitantly, one of them also induced a significant increase in viral translation (>50%). The three remaining aptamers efficiently competed with the binding of the NS5B protein to the CRE. Present findings confirm the potential of the CRE as an anti-HCV target and support the use of aptamers as molecular tools for investigating the functionality of RNA domains in viral genomes.


Relevant safety aspects of raw milk for dairy foods processing.
The concern with food safety in the milk chain begins with the quality of the raw milk. Due to the health hazard that this food can carry when contaminated, the focus of studies has turned to microbiological and chemical contaminants that may be present in raw milk. There is an essential concern about conventional pathogens (Shiga toxin-producing Escherichia coli, Salmonella spp., Listeria monocytogenes, Campylobacter spp., Salmonella spp., and coagulase-positive Staphylococcus spp.) and emerging pathogens (Arcobacter butzleri, Yersinia enterocolitica, Mycobacterium avium ssp. paratuberculosis, Helicobacter pylori, and Cronobacter sakazakii) found in raw milk and dairy products. In addition, a growing public health issue has been raised regarding antimicrobial-resistant pathogens and commensal strains found in milk and dairy products. The antibiotic residues in milk can also damage health, such as allergies, and cause technological problems in dairy products processing. This health issue extends to other chemical contaminants such as heavy metals, pesticides, polycyclic aromatic hydrocarbons, melamine, dioxins, polychlorinated biphenyls, plasticizers, and additives in milk and dairy products. Other chemical substances formed by microorganisms are also of high importance, such as biogenic amines and mycotoxins. Therefore, this chapter aimed to revise and discuss relevant biological and chemical risks to ensure the safety and quality of raw milk and dairy products.


NOD mice and autoimmunity.
The NOD mouse has been an important model of type 1 diabetes and autoimmune diseases for over 20 years. Experimental and genetic manipulations of the NOD mouse have demonstrated a broad susceptibility to multiple autoimmune syndromes. This predisposition to autoimmunity is due to defects in both central and peripheral tolerance. The defect of central tolerance is likely secondary to improper negative selection mediated by the unique MHC Class II molecule, I-A(g7) as well as intrinsic T cell signaling defects. The genetic basis for impaired peripheral tolerance is controlled by over 20 susceptibility loci termed insulin-dependent diabetes (idd) loci. The maintenance of peripheral tolerance is impaired by alterations in T cell signaling and apoptosis. In addition, insufficient co-stimulation from accessory cells, and defective regulatory T cells, may promote the production of autoreactive T cells.


Human stomach carcinoma-specific T cells derived from the tumour-draining lymph nodes.
In this paper we investigate the reactivity pattern of T cells from stomach carcinoma patients against autologous tumour cells. T cells obtained from the tumour environment, tumour-draining lymph nodes and peripheral blood were cloned in 78 patients with stomach cancer and anti-tumour cytotoxic T lymphocytes (CTLs) precursor frequencies were assessed in each sample by using limiting dilution analysis. When tumour-specific CTLs were tested for specific T-cell killing by using only low doses of Interleukin 2 (100 U ml-1), a moderate rate of proliferation frequency of T cells (0.047) and specific cytotoxicity (12%) were observed in lymph node populations. When both IL-2 and autologous tumour cells in mixed lymphocyte tumour cultures (MLTCs) were used for stimulation, a dramatic increase in number (0.1) and in specific lytic activity (46%) could be measured. No effect or specific activity to tumour cells was observed with peripheral blood lymphocytes and tumour-infiltrating lymphocytes.


The prevalence, evolution and chromatin signatures of plant regulatory elements.
Chromatin accessibility and modification is a hallmark of regulatory DNA, the study of which led to the discovery of cis-regulatory elements (CREs). Here, we characterize chromatin accessibility, histone modifications and sequence conservation in 13 plant species. We identified thousands of putative CREs and revealed that distal CREs are prevalent in plants, especially in species with large and complex genomes. The majority of distal CREs have been moved away from their target genes by transposable-element (TE) proliferation, but a substantial number of distal CREs also seem to be created by TEs. Finally, plant distal CREs are associated with three major types of chromatin signatures that are distinct from metazoans. Taken together, these results suggest that CREs are prevalent in plants, highly dynamic during evolution and function through distinct chromatin pathways to regulate gene expression.


[On the state of the budgetary funding of government forensic medical expert institutions in the Russian Federation].
The data on the budgetary funding of state-owned forensic medical bureaus in the Russian Federation for the period from 2005 to 2008 were collected and analysed. The results of the overall estimation and parameters characterizing the level of funding of these expert facilities are presented. Selected state forensic medical bureaus have been ranked based on the level of their financial support.


Concentrations of organochlorine pesticides in placental tissue are not associated with risk for fetal orofacial clefts.
Previous epidemiological studies have shown that prenatal exposure to organochlorine pesticides (OCPs) entails a variety of adverse impacts on fetal health, but it is not yet known whether it is associated with risk for orofacial clefts (OFCs). This study of 103 fetuses or newborns with a diagnosis of OFCs (cases) and 103 healthy newborns without malformations (controls) examined whether prenatal exposure to OCPs, as indicated by their concentrations in placental tissue, is a risk factor for OFCs. No differences were found in the median concentrations of OCPs between cases and controls, with exception of o,p'-dichlorodiphenyldichloroethylene, o,p'-dichlorodiphenyldichloroethane, and total o,p'-dichlorodiphenyltrichloroethane (DDTs), whose concentrations were higher in controls than in cases (Ps < 0.05). Although higher concentrations of placental δhexachlorocyclohexane and isodrin were found to be associated with decreased risk for OFCs in logistic regression, no association was observed in the Bayesian kernel machine regression, a novel statistical model in analyzing exposure mixtures. Women who reported periconceptional folic acid supplementation had lower placental concentrations of DDTs than women who did not. In conclusion, no association between levels of OCPs in placental tissue and risk for OFCs was observed in this population. Supplementation with folic acid may help decrease the levels of DDTs in placental tissue, but further studies are needed to confirm this unexpected finding.


Pulmonary hemodynamics and plasma endothelin-1 during hypoxemia and reoxygenation with room air or 100% oxygen in a piglet model.
The immediate effect on the pulmonary circulation of reoxygenation with either room air or 100% O2 was studied in newborn piglets. Hypoxemia was induced by ventilation with 8% O2 until base excess was <-20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with either room air (n = 9) or 100% O2 (n = 9). Mean pulmonary artery pressure increased during hypoxemia (p = 0.012). After 5 min of reoxygenation, pulmonary artery pressure increased further from 24 +/- 2 mm Hg at the end of hypoxemia to 35 +/- 3 mm Hg (p = 0.0077 versus baseline) in the room air group and from 27 +/- 3 mm Hg at the end of hypoxemia to 30 +/- 2 mm Hg (p = 0.011 versus baseline) in the O2 group (NS between groups). Pulmonary vascular resistance index increased (p = 0.0005) during hypoxemia. During early reoxygenation pulmonary vascular resistance index decreased rapidly to values comparable to baseline within 5 min of reoxygenation in both groups (NS between groups). Plasma endothelin-1 (ET-1) decreased during hypoxemia from 1.5 +/- 0.1 ng/L at baseline to 1.2 +/- 0.1 ng/L at the end of hypoxemia (p = 0.003). After 30 min of reoxygenation plasma ET-1 increased to 1.8 +/- 0.3 and 1.5 +/- 0.2 ng/L in the room air and O2 groups, respectively (p = 0.0077 in each group versus end hypoxemia; NS between groups). We conclude that hypoxemic pulmonary hypertension and plasma ET-1 normalizes as quickly when reoxygenation is performed with room air as with 100% O2 in this hypoxia model with newborn piglets.


Erythrocytosis associated with a placental-site trophoblastic tumor.
We present a case of placental-site trophoblastic tumor associated with erythrocytosis. This 42-year-old woman had persistent amenorrhea and low elevations of her hCG titer after term delivery of a healthy female infant. The woman was noted to have polycythemia of uncertain etiology and was treated with serial phlebotomy. Placental-site trophoblastic tumor was diagnosed and hysterectomy was performed, with subsequent resolution of the polycythemia. Although erythrocytosis has been reported with other gynecologic tumors, this is the first reported association with a placental-site trophoblastic tumor. A role has been suggested for placental lactogen in erythropoiesis during pregnancy based on previous animal studies. Diffuse positive staining for hPL is characteristic of placental-site trophoblastic tumors. We postulate that hPL may have played an ancillary role to erythropoietin in the erythrocytosis demonstrated in this case. Spider angiomata and splenomegaly are interesting clinical features previously described in association with placental-site trophoblastic tumors, and were demonstrated in this patient.


Production of biogenic amines and divercin V41 in cold smoked salmon inoculated with Carnobacterium divergens V41, and specific detection of this strain by multiplex-PCR.
The objective of this study was to determine the technological behaviour (implantation and biogenic amines production) of Carnobacterium divergens V41, an anti-Listeria bacteriocin producer (divercin V41), after inoculation in cold smoked salmon (CSS). Implantation of the strain was followed by multiplex-PCR during 27 days of storage at 4 degrees C, and biogenic amines were quantified by HPLC. It was found that the strain was able to develop quite well in CSS among lactic wild flora. Divercin V41 (400 AU ml-1) was produced in CSS, and the biogenic amine content was not modified by inoculation of the bacteria. Carnobacterium divergens V41 is a safe, interesting, bioprotective agent. This strain could potentially be used for efficient prevention of L. monocytogenes growth in CSS.


Health behavior practice among understudied Chinese and Filipino Americans with cardiometabolic diseases.
Lifestyle modification and health behavior practice among the individuals with cardiometabolic diseases (CMD) are important for secondary prevention and disease control. This study was designed to investigate and compare health behavior practices among Chinese and Filipino Americans with CMD. Three hundred seventy-four Asian Americans (211 Chinese and 163 Filipino) who reside in the greater Philadelphia region and had either CMD or no identified disease were included in the study. Information on smoking, alcohol intake, physical activity, and salt and sweets consumption was collected, as well as demographic and acculturative characteristics. Of the 374 participants, 241 (64.4%) had CMD and 133 (35.6%) had no identified disease. The majority of Chinese and Filipino Americans with CMD failed to meet the dietary and physical activity guidelines, and only a small percentage of them restricted their amount of salt added to food and amount of sweets consumption. Compared to participants with no disease, Chinese participants with CMD were more likely to "never" add salt to food (AOR 4.42 compared to "frequently"). Filipino Americans with CMD were less likely to be those who "never" consume sweets than those who frequently consume sweets (AOR = 0.12). Among the participants with CMD, Chinese participants with CMD were less likely to restrict drinking (AOR 0.11) than Filipinos with CMD. The findings suggest that tailored interventions for Chinese and Filipino Americans with CMD should be developed to enhance their compliance to behavioral guidelines to prevent further disease progression and complications.


PCS-I--a point counting stereology program for cell biology.
PCS-I is a versatile BASIC program designed to collect and process stereological point counting data from electron micrographs of cells. The program can accept the point counts from three sources: (i) a set of user-definable keys programmed as counters; (ii) a numeric pad that enters counts line by line; and (iii) a data tape cartridge. The program calls for all the information needed to solve stereological equations and then helps the user to interpret the suitability of the sample size by drawing error curves. The coefficients of the stereological equations and the output headings can be readily modified to accommodate a new set of experimental parameters, which gives a substantial amount of flexibility to the program. PCS-I is easy to use and offers a practical solution to the problem of data management for biological stereology.


Correction algorithm for finite sample statistics.
Assume in a sample of size M one finds M(i) representatives of species i with i = 1..N*. The normalized frequency pi* triple bond Mi/M, based on the finite sample, may deviate considerably from the true probabilities p(i). We propose a method to infer rank-ordered true probabilities r(i) from measured frequencies M(i). We show that the rank-ordered probabilities provide important informations on the system, e.g., the true number of species, the Shannon- and the Renyi-entropies.


Can mechanical ventilation strategies reduce chronic lung disease?
Chronic lung disease (CLD) continues to be a significant complication in newborn infants undergoing mechanical ventilation for respiratory failure. Although the aetiology of CLD is multifactorial, specific factors related to mechanical ventilation, including barotrauma, volutrauma and atelectrauma, have been implicated as important aetiologic mechanisms. This article discusses the ways in which these factors might be manipulated by various mechanical ventilatory strategies to reduce ventilator-induced lung injury. These include continuous positive airway pressure, permissive hypercapnia, patient-triggered ventilation, volume-targeted ventilation, proportional assist ventilation, high-frequency ventilation and real-time monitoring.


Encapsulation of indole-3-carbinol in Pickering emulsions stabilized by OSA-modified high amylose corn starch: Preparation, characterization and storage stability properties.
The stability of hydrophobic bioactive compound indole-3-carbinol (I3C) is a challenge for application. In this work, Pickering emulsions were prepared to encapsulate I3C. As the emulsifier, high amylose corn starch was pretreated by acid hydrolysis, afterwards modified by different concentrations of octenyl succinic anhydride (OSA), and their emulsions were evaluated. The XRD, SEM and FTIR results indicated the successful modification. ζ-potential, mean droplet size and emulsification index (EI) of the emulsions confirmed that modified starch with a higher degree of substitution (DS) was more effective for enhancing the storage stability. The results of encapsulation efficiency (EE) and retention degree of I3C after 14 d also proved the assumption. Moreover, the Pickering emulsions protected I3C against ultraviolet light and achieved controlled release in vitro. The food-grade Pickering emulsion loading I3C is promising to be used as a nutrient or dietary supplement for food applications.


Quantifying Facial Distortion in Modern Digital Photography.
Advancements in digital cameras and the advent of smartphones have magnified the importance of clinical photography in facial plastic surgery. Here, we aim to examine the effect of different camera types, focal lengths, and distances from subjects on facial distortion. Twelve subjects underwent a series of frontal photographs using a smartphone camera and a full-frame digital single-lens reflex camera. Photos were captured at six distances from the subject. Seven focal lengths were used at each distance for the full-frame camera. Measurements of facial landmarks were made for each photo, with those made at 60 inches using the full-frame camera considered the gold standard and used for comparison. Distortion of facial features using the full-frame camera occurred when photos were captured 8 inches away using short focal lengths. A 12%-19% increase in vertical stretching of the midface occurred when using focal lengths of 24, 35, and 50 mm (p < 0.05 for all). The same features were distorted when a smartphone camera was used at 8 inches (18% increase, p < 0.01) and 12 inches (12% increase, p < 0.03). Distortion of midfacial features using both smartphones and full-frame cameras occurs with short, 'selfie' distances between the camera and subject. Level II Laryngoscope, 2023.


Photodynamic therapy with m-tetrahydroxyphenyl chlorin for high-grade dysplasia and early cancer in Barrett's columnar lined esophagus.
Many patients with high-grade dysplasia and localized adenocarcinoma in Barrett's esophagus have localized disease but are either unfit for major surgery or decline esophagectomy. Photodynamic therapy with the powerful photosensitizer m-tetrahydroxyphenyl chlorin may be a nonsurgical therapeutic option. This is a pilot study to evaluate the efficacy and complications of m-tetrahydroxyphenyl chlorin photodynamic therapy. The design is a case series of 19 consecutive patients at a tertiary referral unit with a special interest in photodynamic therapy. The study included 7 patients with high-grade dysplasia and 12 with early esophageal cancer, who had refused or were unfit for esophagectomy. Three days after photosensitization with 0.15 mg/kg m-tetrahydroxyphenyl chlorin, red or green light was delivered endoscopically when using either a bare fiber or a diffuser device. Results were assessed by endoscopic surveillance. By using red light via the diffuser, 4/6 patients with cancer and 3/4 with high-grade dysplasia were successfully treated with photodynamic therapy alone. When using the bare-tipped fiber, there was one procedure-related death and only 1/5 patients with cancers were successfully treated. Two others were downgraded to high-grade dysplasia. With green light delivered via a diffuser, 0/3 patients with high-grade dysplasia are in long-term remission. Two serious complications arose (including one death) from taking multiple biopsy specimens too soon after therapy. Two esophageal strictures occurred. Photodynamic therapy with m-tetrahydroxyphenyl chlorin is, potentially, a valuable therapeutic option for localized esophageal neoplasia. Red light via a diffuser device appears to be the most effective light-delivery technique. Biopsy specimens should not be taken for at least 2 months after treatment.


Papillary muscle and left ventricle show different contractile and metabolic responses during myocardial stunning.
We conclude that a global ischemic/hypoxic insult results in a heterogeneous response of mechanical and mitochondrial performance in isolated Langendorff-perfused hearts. The results warn against the use of models of stunning in which stunning is determined for only one part (e.g. left ventricle) and effects of stunning are analyzed in other parts (e.g. right ventricular muscle). The results further suggest that some parts of the myocardium under some mechanical loading conditions can withstand 15 min of interrupted oxygen supply without strong negative effects on contractile function and the response time of oxidative phosphorylation.


Proposed grading system of unilateral cleft lip to predict surgical challenges.
It is a common practice to subjectively categorize cleft lip deformities into narrow and wide cleft. The proposed grading of unilateral cleft lip can serve as a predictive factor of the difficulties to be encountered during repair and the expected outcome of surgery. This was a 5-years retrospective study of the records of 32 patients with unilateral cleft lip that presented to a single surgical unit. We grouped the patients based on the age at surgery. We calculated the alar base width ratios of the cleft to non-cleft sides, and this was used for grading. We graded the clefts using ratio of 1.00-1.50 for mild cleft, 1.51 to 2.00 for moderate cleft, 2.01-3.00 for severe cleft, and >3.00 for extensive cleft lip. The youngest child was 1 month old, while the oldest was 50 years. Majority of the patients (17) were older than 2 years at the time of surgery. Only nine babies (28.1% of the patients) were able to have their surgery done within the age of 6 months. Those that had extensive unilateral cleft lip were 10 (31.3%). However, a total of 18 (56.3% of the patients) had cleft lips that were either mild or moderate grade. This grading of unilateral cleft lip helps in objective preoperative assessment of the severity and in predicting the difficulty expected during lip repair. It is also helpful in assigning clefts to trainees and in determining which patients should be referred to an experienced surgeon.


Bacteraemia and meningitis among hospital patients with diarrhoea.
To characterize bacteraemia and meningitis in diarrhoeal patients, the records of 3395 blood cultures and 120 cerebrospinal fluid (CSF) cultures from 6132 patients admitted with diarrhoea to the Clinical Research Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh during 1989 were analysed. Microorganisms were isolated from 12% (417 of 3395) of blood cultures and 9% (11 of 120) of CSF cultures. Children below 5 years of age represented 80% of all patients who had blood cultures and 82% of those who had CSF cultures made. The nutritional status was significantly lower in patients who had positive blood cultures than in those who had negative cultures. 23% (97 of 417) of patients with positive blood cultures and 45% (5 of 11) with positive CSF cultures died. Deaths occurred twice as often among patients who had organisms isolated than among those who had no organisms isolated from blood cultures. The organisms isolated from blood cultures which predicted most deaths were Pseudomonas aeruginosa, Neisseria meningitidis, Escherichia coli and Klebsiella sp., and they were multiresistant. We conclude that bacteraemia and meningitis remain serious complications associated with diarrhoea, especially in malnourished children; the therapeutic problem is further complicated by multiple drug resistance of the isolates.


Substrate and metal control of barrier heights for oxo transfer to Mo and W bis-dithiolene sites.
Reaction coordinates for oxo transfer from the substrates Me(3)NO, Me(2)SO, and Me(3)PO to the biologically relevant Mo(IV) bis-dithiolene complex [Mo(OMe)(mdt)(2)](-) where mdt = 1,2-dimethyl-ethene-1,2-dithiolate(2-), and from Me(2)SO to the analogous W(IV) complex, have been calculated using density functional theory. In each case, the reaction first proceeds through a transition state (TS1) to an intermediate with substrate weakly bound, followed by a second transition state (TS2) around which breaking of the substrate X-O bond begins. By analyzing the energetic contributions to each barrier, it is shown that the nature of the substrate and metal determines which transition state controls the rate-determining step of the reaction.


pH-dependent microbial niches succession and antibiotic resistance genes distribution in an oxygen-based membrane biofilm reactor treating greywater.
System pH is found to crucially affect biofilm growth and microorganisms' activity in the biofilm-based wastewater treatment system. This study investigated the pH-dependent pollutants removal, microbial niches succession and antibiotic resistance genes (ARGs) accumulation in an oxygen-based membrane biofilm reactor treating greywater. Results indicated that neutral conditions achieved the highest biofilm concentration and living cells, which enabled the highest pollutants removal rates; multifarious functional groups in biofilm enabled pollutants adsorption, which favored its continuous bio-removal. Microbial communities under acidic condition (pH = 5.0) were significantly different with that under other conditions (p < 0.05). The neutral and alkaline niches (pH = 7.0 and 9.0) were predominant by organics biodegradation and nitrogen reduction bacteria (e.g. Sphingobacteriales, Pseudomonas, Flavobacterium and Phenylobacterium), but which were significantly dropped under acidic conditions, leading to the declined reactor performance. ARGs in biofilm (predominant by korB, intI-1, sul1 and sul2) were much higher than that in the cell-free liquid and the target ARGs accumulation (korB, intI-1, blaCTX-M, qnrS) had nearly linear positive relationships (R2 > 0.95, P < 0.01) with biofilm-attached linear alkylbenzene sulfonate (LAS). LAS stimulate ARGs proliferation in functional microorganisms (korB, sul-1 and intI-1 were significantly associated with related microbial genus) and biofilm played a key role in ARGs dissemination. The relatively low ARGs in both biofilm and effluent under neutral conditions suggested that pH controlling can be an effective strategy to inhibit ARGs dissemination and proliferation in the system.


First Record and Larval Habitat Description of Culex (Melanoconion) pilosus from Buenos Aires Province, Argentina.
Larvae of Culex (Melanoconion) pilosus were collected during February-April 2014 in temporary pools in "Bosques de Ezeiza," a large forested park, near Buenos Aires city, Argentina. This is the first record in Buenos Aires Province, extending the distribution of this species 380 km to the south. Regarding habitat use, Cx. (Mel.) pilosus is a generalist, although a slight association of larval abundances with pools of lower pH and higher vegetation cover was observed. The comparison of larval instars of Cx. (Mel.) pilosus with those of other genera suggests a life-history strategy similar to that of floodwater mosquitoes.


Resonance Raman characterization of hog thyroid peroxidase. An SERRS study.
Resonance Raman (RR) spectra of hog thyroid peroxidase (TPO) were observed for the first time and compared with those of lactoperoxidase (LPO) and horseradish peroxidase (HRP). Since TPO purified by monoclonal antibody-assisted immunoaffinity chromatography was strongly fluorescent, the surface enhancement technique using Ag colloid adsorption was used for the oxidized form, but ordinary RR spectra could be obtained for the reduced form. The RR spectra of TPO were distinct from those of HRP in both the oxidized and reduced states and indicated the presence of six-coordinated iron-protoporphyrin.


Oxygen-Induced Retinopathy in the Rat: An Animal Model to Study the Proliferative Retinal Vascular Pathology.
Diabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. There are numerous animal models available for developing new ocular therapeutics and drug screening and to investigate the pathological processes involved in DR. Among those animal models, the oxygen-induced retinopathy (OIR) model, though originally developed as a model for retinopathy of prematurity, has also been used to investigate angiogenesis in proliferative DR with the phenomenon of ischemic avascular zones and pre-retinal neovascularization it demonstrated. Briefly, neonatal rodents are exposed to hyperoxia to induce vaso-obliteration. Upon removal from hyperoxia, hypoxia develops in the retina that eventually results in neovascularization. The OIR model is mostly used in small rodents such as mice and rats. Here, we describe a detailed experimental protocol of rat OIR model and the subsequent assessment of abnormal vasculature. By illustrating the vasculoprotective and anti-angiogenic activities of the treatment, OIR model might advance to a new platform for investigating novel ocular therapeutic strategies for DR.