Reversibility of spermine-induced intestinal maturation in the rat.
In the present investigation, the reversibility of spermine-induced precocious intestinal maturation was studied. Neonatal rats received either saline or spermine (4 mumol, twice daily) solution orally on the 11th and 12th postnatal day. They were killed on the 13th, 14th, 15th, 16th, and 17th postnatal days. After the small bowel was removed, it was either divided into three equal parts or prepared for electrophoretic analysis. Histological examination, protein content measurement, and disaccharidase activity estimation were performed on each part of the intestine. Spermine administration was shown to induce structural and mucosal enzyme changes characteristic of postnatal maturation. This phenomenon, which was generally clearly observed in 13- and 14-day-old rats, then became less apparent in 15- and 16-day-old animals. Differences were noted according to the segment of intestine or the biochemical parameter analyzed. When rats were 17 days old, no significant differences generally existed between control and spermine-treated rats. If the 140- to 150-kDa proteins, isolated by electrophoresis, are assumed to represent the subunits of the sucrase-isomaltase complex, the results obtained indicate that spermine induces a modification of the concentration of this complex. When compared to values obtained in adult rats, the concentration of the complex was approximately three times higher in spermine-treated 13-day-old rats, while no differences were found in spermine-treated 14-day-old rats. Further, similar concentrations were found in control and spermine-treated rats with an age of 17 days. These results suggest that spermine-induced precocious intestinal maturation is reversible when spermine treatment is stopped.


A Rare Case of Xanthogranulomatous Cystitis Mimicking Bladder Malignancy in Nigeria: A Case Report and Review of Literature.
Xanthogranulomatous cystitis (XC) is a very rare urinary bladder condition, of unknown etiology. It may mimic bladder malignancy; therefore, histopathologic assessment is crucial in diagnosis. We report a case of a 38-year-old female who presented with persistent, painless hematuria and a strong consideration of bladder malignancy clinically and on cystoscopy. However, on histopathologic evaluation, the rare diagnosis of XC was made. She received a course of antibiotics and has remained asymptomatic after four months of follow-up. To the best of our knowledge, this is the first reported case of XC in Nigeria and Africa.


Pirfenidone inhibits obliterative airway disease in mouse tracheal allografts.
Obliterative bronchiolitis (OB) is the histologic correlate of chronic airway rejection, which remains the most significant cause of death in long-term survivors of lung transplantation. Using an established murine heterotopic tracheal transplant model of chronic airway rejection, the effects of the oral anti-fibrotic agent pirfenidone on development of the OB-like lesion were evaluated. Tracheas from BALB/c mice were implanted into the sub-cutaneous tissue of C57BL/6 mice, and the allografts were evaluated morphologically for airway rejection changes and immunohistochemically for transforming growth factor (TGF)-beta at 16 or 28 days after transplantation. In addition, the potential additive effects of pirfenidone in combination with 2 immunosuppressive agents, cyclosporine or rapamycin, was evaluated. Compared with untreated controls, pirfenidone-fed mice showed less epithelial cell injury and luminal granulation tissue and fibrosis. Plasma TGF-beta levels and local TGF-beta expression based on immunohistochemistry were decreased in the pirfenidone-treated animals. Pirfenidone given on Day 9 or 16 post-transplant through Day 28 resulted in no significant improvement compared with controls. There was no significant additive effect of pirfenidone in combination with cyclosporine, whereas pirfenidone plus rapamycin demonstrated additive protection against the development of the obstructive airway lesion. In aggregate, these results show that the anti-fibrotic agent pirfenidone inhibits the development of the OB-like lesion in this mouse model of human chronic airway rejection, and that these effects may be mediated by TGF-beta. The results also suggest that pirfenidone may be worthy of investigation in human lung transplant recipients at high risk of developing OB.


Targeting YAP1/TAZ in nonsmall-cell lung carcinoma: From molecular mechanisms to precision medicine.
Accumulating evidence has underscored the importance of the Hippo-YAP1 signaling in lung tissue homeostasis, whereas its deregulation induces tumorigenesis. YAP1 and its paralog TAZ are the key downstream effectors tightly controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In solid tumors, Hippo-YAP1 crosstalks with other signaling pathways such as Wnt/β-catenin, receptor tyrosine kinase cascade, Notch and TGF-β to synergistically drive tumorigenesis. As YAP1/TAZ expression is significantly correlated with unfavorable outcomes for the patients, small molecules have been developed for targeting YAP1/TAZ to get a therapeutic effect. In this review, we summarize the recent findings on the deregulation of Hippo-YAP1 pathway in nonsmall cell lung carcinoma, discuss the molecular mechanisms of its dysregulation in leading to tumorigenesis, explore the therapeutic strategies for targeting YAP1/TAZ, and provide the research directions for deep investigation. We believe that detailed delineation of Hippo-YAP1 regulation in tumorigenesis provides novel insight for accurate therapeutic intervention.


Acute effects of mitoxantrone on the template activity of isolated nuclei from the T-47D human breast tumor cell line.
The effect of mitoxantrone on the template activity of nuclei isolated from the T-47D human breast tumor cell line was investigated. The results suggest that mitoxantrone significantly inhibits total RNA synthesis of these nuclei in a concentration-dependent manner. At low drug concentrations (10(-9) M and 10(-7) M) RNA synthesis was inhibited by 21.9% and 41% compared to control values, respectively. Greater inhibition was observed when the mitoxantrone concentration was increased to 10(-5) M or 10(-4) M (56% and 77%, respectively). Experiments utilizing alpha-amanitin revealed that mitoxantrone inhibits RNA polymerase II activity in a concentration-dependent manner.


Vogt-Koyanagi-Harada syndrome and ulcerative colitis.
The Vogt-Koyanagi-Harada (VKH) syndrome is an uncommon disorder characterized by uveitis and neurologic and cutaneous abnormalities, including tinnitus, vertigo, headache, meningoencephalitis, vitiligo, alopecia, and poliosis. The VKH syndrome has been reported to occur in association with other autoimmune disorders. We report a case of a patient with severe ulcerative colitis who developed VKH syndrome. We postulate that the patient's history of a traumatic brain injury might have been responsible for an abnormal "immunologic milieu" and the occurrence of ulcerative colitis, VKH syndrome, and severe reactive arthritis.


Characterization of milk and soy phospholipid liposomes and inflammation in 3T3-L1 adipocytes.
Milk phospholipids (PL) are valuable dairy components that appear to impart human health benefits, including improved cognitive function in infants and adults. The commercial food industry uses primarily plant-based sources of PL, such as soy lecithin. However, it remains unclear whether different compositions of PL from different dietary sources, such as milk, convey the same benefits. We hypothesized that PL derived from bovine milk or soy have differing physiological effects in terms of inflammation due to their differences in composition. The objectives of this study were to characterize milk and soy liposomes by their physicochemical properties and composition and to evaluate their effects in vitro by means of inflammatory gene expression analyses. Milk and soy phospholipid large unilamellar vesicles (MPL-LUV and SPL-LUV, respectively) prepared using thin-film hydration coupled with extrusion were similar in terms of structure, size, and stability; however, they differed significantly in composition. The 3T3-L1 adipocytes were selected for this work because adipocytes are the main site of uptake, synthesis, modification, and breakdown of lipids and are important inflammatory mediators in mammalian systems. In this work, these cells exposed to both liposome varieties showed high biocompatibility and low cytotoxicity up to concentrations of 0.5 mg/mL as measured by colorimetric MTT and lactate dehydrogenase assays. Furthermore, SPL-LUV showed trends toward stimulating inflammation compared with MPL-LUV as measured by expression of 2 proinflammatory cytokines, monocyte chemoattractant protein-1 (MCP-1) and IL-6. Expression of MCP-1 significantly increased 1.82-fold relative to the control upon SPL-LUV treatment, with similar trends for IL-6 (increased 1.59-fold). The MPL-LUV showed relatively no change in cytokine expression. The results obtained in this work suggest that the methodology used to prepare LUV and the composition and proportion of milk PL are important in measuring cell physiology changes and inflammatory status in mammalian cells.


Immunohistochemical studies on human brain tumors using anti-Leu 7 monoclonal antibody in paraffin-embedded specimens.
Using the four-step peroxidase-antiperoxidase (PAP) method, the presence of the antigen recognized with anti-Leu 7 monoclonal antibody was investigated in paraffin-embedded human brain tissue and tumors. The antigen was demonstrated in the myelin sheaths, oligodendrocytes, and some choroid plexus cells in normal brain and in oligodendrogliomas, some astrocytomas and choroid plexus papillomas. The technique can be used to identify normal and neoplastic oligodendrocytes.


Gynecologic oncology care in the world of accountable care organizations.
Accountable Care Organizations (ACOs) are an example of alternative payment models that are becoming increasingly common in our healthcare system. ACOs focus on increasing value through cost reduction and improved outcomes, and historically focus on Medicare patients within primary care practices. As ACOs grow, attention will likely turn to costly subspecialty care as an area for improvement and standardization. This brief communication addresses the potential benefits and consequences of ACOs on Gynecologic Oncologists and for patients with gynecologic malignancies.


[Superglue instead of eye ointment; the sealed eye: often frightening and painful, generally ends well].
Not infrequently, patients mistakenly put glue in their eye. This often induces considerable emotional and physical reaction. A 20-year-old man came to the Emergency Department at night because he had mistaken a tube of superglue for his eye ointment and instilled the glue into his right eye. All the glue was removed, as were most of his eyelashes. The glue-induced corneal abrasion healed completely and the patient did not sustain any permanent injury. Despite the considerable dismay and severe pain caused by mistakenly introducing superglue into the eye, most cases have a favourable outcome.


[Long-term changes on nasal tip in rhinoplasty patients operated with the new domes technique and the banner technique].
Anatomy, surgical manoeuvres, scarring and physiologic nasal aging determine the final outcome of nasal tip on rhinoplasty patients. Post-operative nasal tip changes in 182 rhinoplasty patients operated on by the same surgeon and with a minimum one year of follow-up were studied. A personal interview was arranged with all patients and facial photographs were taken. Nasal tip rotation, projection and definition were measured. After multivariate analysis, surgical manoeuvres with a statistical impact on the long-term outcome of the nasal tip were dome lateralization greater than 3 mm, columellar strut and shield graft. Cartilage reshaping and tip grafting provide consistent long-lasting results in nasal tip surgery.


The placebo dilemma.
Placebos have been used since about 1950 in evaluation and interpretation of drug efficacy, especially of new drugs, and in comparison with existing compounds to establish their clinical therapeutic value. There are a number of problems connected with use of an "inert nothing" the informed consent, which is required in a human experiment, the doctor's consciousness of deceitful behaviour, the potential risk for the patient and the doctor, the high effect rate of placebos (+/- 35%), unexpected side-effects, dependency of patients on placebos, discovery by the patient of the placebo treatment, factors independent of the medication, such as the doctor's bias, the nurses influence, the significance of colour, the inconsistency of placebo-reactor or non-reactor types and the genetic state of the patient, as well as the problems associated with a double blind test, which can hardly be used when a patient has previously received a medicine, such as morphine, with its euphoric effect, and the colour change produced in urine by drugs like rifampicin or riboflavin. Only a well-trained and experienced clinical observer should employ a placebo in establishing the therapeutic value of drugs whilst avoiding undesirable pitfalls.


Detecting groups of coherent voxels in functional MRI data using spectral analysis and replicator dynamics.
To investigate the relationship between functional MRI (fMRI) time series in the human brain, combining fMRI spectral analysis and replicator dynamics. Simulated and real fMRI time courses were investigated using the bivariate spectral coherence. Coherence values were placed in coherence matrices encoding the relationship between the time courses. Groups of maximally coherent voxels were detected using replicator dynamics. Results were compared to a former approach called number of coherent voxels (NCV). NCV critically depends on a threshold that has to be chosen in advance. The lower this threshold, the larger the detected group. Using higher NCV thresholds in our simulations, the method did not detect all voxels that were constructed to have a high coherence among each other. In contrast, the replicator process found the whole group in all simulations. The application of replicator dynamics to spectral matrices is a reliable method for detecting groups of maximally coherent voxels. A replicator process is able to determine groups of voxels with the property that each voxel in the group exhibits a high coherence with every other group member. In contrast to the NCV approach, this method is parameter-free and does not require the a priori selection of a reference voxel.


The Role of Patient-Reported Outcomes in Sleep Measurements.
Several questionnaires aka patient-reported outcome measures (PROMs) have been developed for specific use in sleep medicine. Some PROMS are "disease-specific," that is, related to a specific sleep disorder, whereas others are generic. These PROMS constitute a valuable add-on to the conventional history taking. They can be used in the areas of research, clinical practice, and quality of health care appraisal. Still, these instruments have inherent limitations, requiring proficient application in the various areas of interest. Disease-specificity includes a risk for nosologic bias that may confound diagnostic and therapeutic results. Future research should provide solutions for shortcomings of presently available questionnaires.


Improving Machine Learning Technology in the Field of Sleep.
The authors discuss the challenges of machine- and deep learning-based automatic analysis of obstructive sleep apnea with respect to known issues with the signal interpretation, patient physiology, and the apnea-hypopnea index. Their goal is to provide guidance for sleep and machine learning professionals working in this area of sleep medicine. They suggest that machine learning approaches may well be better targeted at examining and attempting to improve the diagnostic criteria, in order to build a more nuanced understanding of the detailed circumstances surrounding OSA, rather than merely attempting to reproduce human scoring.


A meta-analysis of GFR slope as a surrogate endpoint for kidney failure.
Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min-1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82-1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25-0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression.


Circulatory function at sub-zero temperature: venous responses to catecholamines and angiotensin II in the Antarctic fish Pagothenia borchgrevinki.
Catecholamines increase arterial pressure by increasing cardiac output (Q) and stroke volume (V(s)), while angiotensin II (ang II) also increases vascular resistance (R(sys)) in the Antarctic fish Pagothenia borchgrevinki. Adrenaline, phenylephrine and ang II (Asn(1), Val(5)) were injected into P. borchgrevinki. Cardiovascular variables, including central venous pressure (P(cv)) and mean circulatory filling pressure (P(mcf); an index of venous capacitance), were recorded to investigate if venous vasoconstriction can explain the increased V(s) and Q and the arterial pressor response in this species. Routine P(cv) and P(mcf) were 0.11+/-0.01 and 0.18+/-0.02 kPa, respectively. All of the drugs caused moderate increases in P(cv) and P(mcf) and the responses were attenuated after alpha-adrenergic blockade with prazosin. Although dorsal aortic pressure (P(da)) also increased in response to all agonists, the mechanisms differed. Adrenaline caused sustained increases in V(s) and Q, while R(sys) only rose transiently. Ang II had a slower effect than adrenaline and increased both R (sys) and Q, while phenylephrine only increased R(sys). This study demonstrates that P(cv) is positive and controlled by an alpha-adrenergic mechanism in P. borchgrevinki. However, given the relatively small venous response to adrenaline it seems more likely that the increases in V(s) and Q from this agonist are due to direct effects on the heart.


The ActivityStat hypothesis: the concept, the evidence and the methodologies.
The ActivityStat hypothesis suggests that when physical activity is increased or decreased in one domain, there will be a compensatory change in another domain, in order to maintain an overall stable level of physical activity or energy expenditure over time. The ActivityStat debate is gaining momentum in the literature and most of the research to date is based on observational studies. The objective of this paper is to conceptually clarify the ActivityStat hypothesis and to examine the experimental research aiming to demonstrate or refute compensation using a systematic review process. A systematic review was conducted using electronic database searches with the aim of detecting studies experimentally investigating the ActivityStat hypothesis or compensation in physical activity or energy expenditure. Included studies were critically appraised using a specifically designed tool to address the conceptual considerations of the ActivityStat hypothesis. Searches identified 28 studies that met the inclusion criteria. Publications spanned 26 years and had multiple methodological approaches, including randomized and non-randomized controlled trials, crossover designs, cluster randomized controlled trials and pre-post trials. Populations of the included studies ranged from children, to adults and the elderly, across a range of weight statuses and used both aerobic, resistance and mixed-exercise interventions. The timeframe of interventions ranged from 1 day to 4 years and outcomes were measured using doubly labelled water, accelerometry, heart rate monitoring, resting metabolic rate, indirect calorimetry, pedometry, subjective recall questionnaire and the activity-related time index. Fifteen of 28 included studies provided evidence of compensation, while 13 did not. Subgroup analyses by population, type and duration of intervention, weight status and study quality also showed mixed findings. There is a substantial body of experimental literature investigating compensation that has largely been overlooked in the ActivityStat debate. However, this evidence is currently inconclusive and lacks a cohesive approach to the question of an ActivityStat. Recommendations for the design of future experimental research investigating the ActivityStat hypothesis are presented.


Cerebrospinal fluid proteins in muscular dystrophy patients.
We analyzed and quantified the microcomponents of protein fractions in the cerebrospinal fluid of patients with various types of muscular dystrophy. The degenerative pattern is characterized by an increase in the prealbumin fraction and a decrease in the gamma-globulin fraction as shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, gamma-globulin fraction, and myelin basic protein is shown in the myotonic dystrophy. In addition to the lowness of IQ, and the abnormality of EEG and brain CT, abnormal CSF proteins obviously suggest the presence of CNS involvement in muscular dystrophy.


Controlled Delivery of Dutasteride Using Dissolvable Microarrays: Initial Formulation and In Vivo Evaluation.
Dutasteride is prescribed as a once-daily oral capsule for the treatment of symptomatic benign prostatic hyperplasia. As an alternative and patient-focused drug product, this laboratory evaluated the potential to deliver dutasteride in a controlled/sustained manner when formulated as a microarray. The low oral dose, low aqueous solubility, and slow rate of elimination of dutasteride were considered ideal properties which may enable a once-weekly microarray option for patients. The concept of sustained release was initially proven in mini-pigs whereby simple intradermal administration of a nanomilled dutasteride suspension (0.12 mg/kg) was associated with an exposure period of at least 1 month. Dissolvable microarrays were successfully manufactured using a nanomilled suspension and were administered to rats at doses up to 0.32 mg/kg. In these studies, serum dutasteride was quantifiable for approximately 2 weeks after a single application. In silico modeling of the rat data using a two-compartment intradermal model was conducted and predicted that, in humans, a once-weekly dose of 2 mg, given as a microarray, could deliver cumulative and therapeutically relevant levels of dutasteride in a manner which is comparable to that observed with the current oral regimen.


Antileishmanial and immunomodulatory effects of the essential oil from Tetradenia riparia (Hochstetter) Codd.
Cutaneous leishmaniasis usually presents therapeutic resistance to antimonials, and the existing therapies for leishmaniasis have many adverse effects and toxicity. Natural products may be regarded as possible candidates for alternative leishmaniasis treatment. The plant Tetradenia riparia has shown promise for the treatment of infectious diseases in folk medicine. We evaluated the antileishmanial activity of an essential oil from T. riparia (TrEO) and the modulatory effects of TrEO on cytokine modulation by peritoneal fluid cells that were infected with L. (L.) amazonensis. Peritoneal fluid cells were infected with Leishmania and incubated with TrEO (30 ng/mL) for 3, 6, and 24 h. Cytokines were screened using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and flow cytometry. Antileishmanial activity was evaluated at 24 h by microscopic counting and quantitative PCR (qPCR). TrEO treatment induced the death of 50% of Leishmania amastigotes (indicated by microscopic counting) and 91% of the parasite load (indicated by qPCR). TrEO inhibited some of the most critical cytokines for parasite growth and the establishment of infection, including granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), IL-10, and tumour necrosis factor. The parasite inhibited interferon-γ and IL-12, and TrEO blocked this inhibition, indicating that these cytokines are critical for activating mechanisms associated with the death and elimination of the parasite. These results suggest that TrEO may be an alternative leishmaniasis therapy when considering its antileishmanial and immunomodulatory activity.


Conserved exon-intron organization in two different caerulein precursor genes of Xenopus laevis. Additional detection of an exon potentially coding for a new peptide.
From a genomic library of Xenopus laevis, two genes coding for different preprocaeruleins have been isolated and sequenced. These correspond to the type I and type III precursors analyzed previously at the cDNA level [Richter, K., Egger, R. and Kreil, G. (1986) J. Biol. Chem. 261, 3676-3680]. The type III gene comprises eight exons; the type I apparently contains eight exons as well, of which six have been sequenced. The genetic information for the dekapeptide caerulein is present on small exons of 45 base pairs. The two genes are highly homologous in their 5'-flanking region, the exon/intron boundaries, and long stretches of intron sequences. A possible scheme for the evolution of this small family of genes through exon and gene duplications is presented. In the type I gene, in place of one of the caerulein exons, a potential exon with conserved splice sites was discovered. If expressed in some frog cells, this exon would code for a new peptide 60% homologous to caerulein.


Listening to vaccine refusers.
In bioethics vaccine refusal is often discussed as an instance of free riding on the herd immunity of an infectious disease. However, the social science of vaccine refusal suggests that the reasoning behind refusal to vaccinate more often stems from previous negative experiences in healthcare practice as well as deeply felt distrust of healthcare institutions. Moreover, vaccine refusal often acts like an exit mechanism. Whilst free riding is often met with sanctions, exit, according to Albert Hirschman's theory of exit and voice is most efficiently met by addressing concerns and increasing the quality and number of feedback channels. If the legitimate grievances responsible for vaccine refusal are not heard or addressed by healthcare policy, further polarization of attitudes to vaccines is likely to ensue. Thus, there is a need in the bioethics of vaccine refusal to understand the diverse ethical questions of this inflammable issue in addition to those of individual responsibility to vaccinate.


Palliative Radiotherapy: Inpatients, Outpatients, and the Changing Role of Supportive Care in Radiation Oncology.
Palliative radiotherapy is an effective treatment in alleviating many symptoms of advanced cancer. Short courses of radiotherapy provide rapid symptom relief and minimize impact on patients. Patients referred for palliative radiotherapy have many concerns beyond radiotherapy; often, these concerns are not fully addressed in traditional radiotherapy clinics. Discussions of prognosis, patient goals, and concerns are areas for improved collaboration. Innovative, dedicated palliative radiotherapy programs have developed over the past 20 years to provide holistic care to patients referred for palliative radiotherapy and have improved patient-focused outcomes. Advanced radiotherapy techniques may provide opportunities to further improve palliative radiotherapy outcomes.


Gonadotropins and prolactin serum levels during the perimenopausal period: correlation with diverse factors.
We studied 490 women aged 35 to 55 years randomly selected from the urban population of León, México. The mean age for the onset of menopause, calculated with a probit regression was 48.5 years. The median of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increased with the rate of menopause women, but the 10th percentile for both hormones did not increase above 15 IU/L in older groups. Meanwhile, prolactin did not change. In menopause women FSH correlated positively with cigarette smoking, and negatively with body mass index. Luteinizing hormone had negative correlation with the number of pregnancies. Most symptoms studied were not associated with menopause or gonadotropins levels, except hot flushes, and the empty nest syndrome. It was concluded that during menopause, FSH increases with the smoking habit, and decreases with overweight.


Development of immunoreagents to ciliary zonules that react with protein components of elastic fiber microfibrils and with elastin-producing cells.
We describe the generation of a monoclonal antibody library to ocular zonule components and the characterization of three monoclonal antibodies: 1) one specific for microfibrillar associated glycoprotein (MAGP), a component of both ocular zonules and microfibrils of elastin fibers, 2) an antibody to an as yet unidentified 70,000 dalton antigen that is present in abundance in the extracellular matrix (ECM) of elastin-producing cells, and 3) an antibody reacting with the 67000 dalton subunit of the elastin receptor. The presence of antigenic determinants common to the ocular zonule and elastic fiber microfibrils suggests that zonules, which can be obtained in relatively pure form, can provide a valuable resource for characterizing proteins common to both microfibrillar structures.


A brief self-persuasion intervention to strengthen health-promoting dietary intentions through autonomous motivation.
Given the prevalence in obesity and other diet-related chronic diseases among adults in America, methods targeting dietary behavior change are essential. Interventions that aim to increase individuals' autonomous (i.e., self-driven) motivation to engage in health-promoting behaviors are highly effective, however, such interventions are difficult to scale. Thus, the current study tested the efficacy of a brief self-persuasion intervention to change participants' dietary goal content and increase intentions to make healthy dietary decisions, through autonomous motivation. The study also investigated the assumption that appearance-based goals decrease health-promoting behavior. The intervention was administered online to female college students (N = 300). Results showed that inspiring health-based and appearance-based goal content led to higher intentions compared to gaining others' approval-based goals, indirectly through higher autonomous motivation. Appearance-based goal content also led to higher intentions compared to a control condition. Results imply that there is promise in using a brief, easily administrable, self-persuasion intervention to increase health-promoting dietary behaviors. Additionally, results reflect that bolstering appearance-based goal content can promote health-promoting behaviors, however, more research is necessary to delineate the parameters of the finding.


Quality evaluation of raw and processed Corni Fructus by UHPLC-QTOF-MS and HPLC coupled with color determination.
Corni Fructus (CF), used for thousands of years in Asia as food and medicine, has different therapeutic effects before and after processing. In the past work, the quality assessment of Corni Fructus focused on the limited chemical compounds and rarely correlated external properties, such as color. The traditional sensory assessment relies partly on human eyes, which is quick but lacks objectivity. On a Shimadzu LC-20AD liquid chromatograph system equipped with a diode-array detector (DAD), we determined six major compounds (gallic acid, 5-hydroxymethyl-2-furaldehyde, morroniside, loganin, sweroside, and cornuside I). The extract was analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) after the solid-phase extraction (SPE) step. Totally 58 compounds in raw and processed Corni Fructus were identified in negative and positive ion modes according to tandem mass spectrometry (MS/MS) fragments. Iridoids, carboxylic acids, tannins, flavonoids, triterpenes, fatty acids, saccharides, phospholipids, polysaccharide, amino acid, amide, furan, catechol, aldehyde, fatty alcohol and vitamin were included. A multivariate statistical analysis based on UHPLC-QTOF-MS filtered 17 differential compounds between raw and processed products. The CM-5 colorimeter was applied for digitizing surface and powder color. The contents of gallic acid, morroniside, loganin, cornuside I, and sweroside significantly correlated with color parameters in raw Corni Fructus, particularly adp* and bdp* , but not in processed products, according to Spearman correlation analysis. MS peak area of four compounds in raw products correlated significantly with color parameters Ldp* , adp* , bdp* , Lpd* , apd* , bpd* , respectively, while three compounds in processed products with Lpd* , apd* , bpd* . It revealed the relationship between compounds and color of Corni Fructus and the crucial compounds to color. In this study, we successfully developed a method for comprehensive quality evaluation of Corni Fructus that combines HPLC, UHPLC-QTOF-MS, and color determination.


Radiomics applications in cardiac imaging: a comprehensive review.
Radiomics is a new emerging field that includes extraction of metrics and quantification of so-called radiomic features from medical images. The growing importance of radiomics applied to oncology in improving diagnosis, cancer staging and grading, and improved personalized treatment, has been well established; yet, this new analysis technique has still few applications in cardiovascular imaging. Several studies have shown promising results describing how radiomics principles could improve the diagnostic accuracy of coronary computed tomography angiography (CCTA) and magnetic resonance imaging (MRI) in diagnosis, risk stratification, and follow-up of patients with coronary heart disease (CAD), ischemic heart disease (IHD), hypertrophic cardiomyopathy (HCM), hypertensive heart disease (HHD), and many other cardiovascular diseases. Such quantitative approach could be useful to overcome the main limitations of CCTA and MRI in the evaluation of cardiovascular diseases, such as readers' subjectiveness and lack of repeatability. Moreover, this new discipline could potentially overcome some technical problems, namely the need of contrast administration or invasive examinations. Despite such advantages, radiomics is still not applied in clinical routine, due to lack of standardized parameters acquisition, inconsistent radiomic methods, lack of external validation, and different knowledge and experience among the readers. The purpose of this manuscript is to provide a recent update on the status of radiomics clinical applications in cardiovascular imaging.


N2O emissions and product ratios of nitrification and denitrification are altered by K fertilizer in acidic agricultural soils.
Potassium (K) fertilizer plays an important role in increasing crop yield, quality, and nitrogen use efficiency. However, little is known about its environmental impacts, such as its effects on emissions of the greenhouse gas nitrous oxide (N2O). A nitrogen-15 (15N) tracer laboratory experiment was therefore performed in an acidic agricultural soil in the suburbs of Wuhan, central China, to determine the effects of K fertilizer on N2O emissions and nitrification/denitrification product ratios under N fertilization. During 15-d incubation periods with a fixed initial N concentration (80 mg kg-1), K application increased average N2O emission rates significantly (1.6-10.8-fold) compared to the control treatment. N2O emissions derived from nitrification and denitrification both increased in K-treated soil, and denitrification contributed more to the increase; its contribution ratio rose from 32% without K fertilizer to 53% with 300 mg kg-1 of K applied. The increase in N2O emissions under K fertilization is probably due to an increase in the activity of denitrifying microorganisms and acid-resistant nitrifying microorganisms caused by higher K+ concentrations and lower soil pH. Combined treatment with potassium chloride (KCl) and N fertilizer produced lower N2O emissions than combined treatment with potassium sulfate (K2SO4) and N fertilizer during 15-d incubation periods. Our results imply that there are significant interaction effects between N fertilizers and K fertilizers on N2O emissions. In particular, combining N fertilizers with fertilizers that reduce soil acidity or contain Cl or K ions may significantly affect agricultural N2O emissions.


Completion of a formal physiotherapeutic scoliosis-specific exercise training program for adolescent idiopathic scoliosis increases patient compliance to home exercise programs.
Physiotherapeutic Scoliosis-Specific Exercise (PSSE) is a conservative approach for management of adolescent idiopathic scoliosis (AIS). Although there is Level I evidence for the efficacy of PSSE, compliance in the teenage population remains in question. The purpose of this study is to investigate the association between completion of formal PSSE training and compliance to prescribed home exercise programs (HEP). Patients with AIS evaluated at our institution between 2013 and 2015 with a minimum of one PSSE session were enrolled. A chart review and questionnaire completed by caregivers was utilized to assess HEP compliance following the final PSSE session at 1 week, 3 months, 1 year, and 2 years. Patients were divided into two groups, those completing formal training (10 or more PSSE sessions), and those who did not complete formal training (fewer than 10 sessions). 81 patients were identified (mean age of 13.1 years; major curve of 31.3°). Patients who completed training demonstrated 50% compliance at 1 week (vs. 25.6% for non-completers, Odds Ratio (OR): 2.9, p = 0.027), 41.2% at 3 months (vs. 18.9% for non-completers, OR: 3.0, p = 0.044), 23.5% at 1 year (vs. 13.5% for non-completers, OR: 2.0, p = 0.281), and 25.7% at 2 years (vs. 13.5% for non-completers, OR: 2.2, p = 0.197). The mean HEP duration (minutes) in patients who completed training was higher at 1 week (80.8 vs. 48, p = 0.010), 3 months (64.6 vs. 23.7, p ≤ 0.001), 1 year (35.3 vs. 22.7, p = 0.270), and 2 years (34.3 vs. 18.9, p = 0.140). Patients who completed PSSE training maintained higher HEP compliance.


A prospective quality evaluation of single donor platelets (SDP) - an experience of a tertiary healthcare center in India.
Quality assurance of single donor platelets (SDP) is incomplete unless clinical response to platelet transfusion is measured. The primary objective of the study was to evaluate the quality of SDP derived from plateletpheresis procedures and to evaluate the response to platelet transfusion. Procedures were performed on 2287 accepted donors while 271 donors were deferred. Platelet count <1.5 lac/μl and hemoglobin <12.5 g/dl were the leading cause of deferral. The median platelet yield in a SDP bag was found to be 3.1×10(11). The median corrected count increment (CCI) and post-transfusion platelet recovery (PPR) were found to be 10110×m(2)/μl and 24.5%, respectively. In India, the criteria for the selection of plateletpheresis donors should be revisited. Based on quality parameters, the Fresenius COM.TEC cell separator is comparable to other cell separators.


Purification and characterization of neurotoxin complex from a dual toxin gene containing Clostridium Botulinum Strain PS-5.
Botulinum neurotoxins are produced as a toxin complex (TC) which consists of neurotoxin (NT) and neurotoxin associated proteins. The characterization of NT in its native state is an essential step for developing diagnostics and therapeutic countermeasures against botulism. The presence of NT genes was validated by PCR amplification of toxin specific fragments from genomic DNA of Clostridium botulinum strain PS-5 which indicated the presence of both serotype A and B genes on PS-5 genome. Further, TC was purified and characterized by Western blotting, Digoxin-enzyme linked immunosorbent assay, endopeptidase activity assay, and Liquid chromatography-Mass spectrometry. The data showed the presence of serotype A specific neurotoxin. Based on the analysis of neurotoxin genes and characterization of TC, PS-5 strain appears as a serotype A (B) strain of C. botulinum which produces only serotype A specific TC in the cell culture medium.


Micropuncture study of changes in glomerular filtration and ion and water handling by the rat kidney during pregnancy.
1. In rats receiving 200 mul. min(-1) sodium chloride, glomerular filtration rate, single nephron glomerular filtration rate, and fractional reabsorption were measured at various points along the nephron, and ionic concentrations measured in early distal tubular fluid in virgin and 6, 12 and 19 day pregnant rats.2. Glomerular filtration increased progressively until the twelfth day of pregnancy. At 19 days of pregnancy the glomerular filtration rate, while still above virgin levels, was reduced below 12 day pregnant levels.3. Single nephron glomerular filtration rates measured in proximal and distal tubules were different at both 12 and 19 days of pregnancy, indicating an alteration of tubuloglomerular feed-back.4. A change in the ratio of glomerular filtration rate: distal single nephron filtration rate indicated a redistribution of glomerular filtrate to juxtamedullary nephrons by the sixth day of pregnancy.5. Fluid reabsorption is similar up to the early distal tubule but it is not possible to say whether reabsorption is the same in proximal tubules. More fluid is reabsorbed by late distal tubules and collecting ducts in 12 and 19 day pregnant animals than in the virgin and 6 day pregnant animals.6. Changes in ion reabsorption by the loop of Henle occurred during pregnancy; sodium reabsorption was increased by the sixth day of pregnancy and potassium reabsorption by the twelfth day.


[Endothelial dysfunction in severe forms of acute renal failure. New approaches to pathogenetic therapy].
To study endothelial function in different variants of acute renal failure (ARF) at various stages of the disease. The study of 36 patients with severe ARF at the stages of oliguria and recovery of diuresis included a clinico-laboratory analysis of characteristics of ARF of various etiology and follow-up of plasmic concentrations of endothelin-1, thromboxan A2 and prostacyclin in different ARF variants at different ARF stages. The oliguric phase of severe ARF ran with significant elevation of the level of vasoconstrictive endothelial hormones (endothelin-1 and thromboxan A2 and a fall of a vasodilator prostacyclin. Recovery of diuresis normalized the above parameters. Mechanisms of ARF development involve endothelial dysfunction manifesting with alteration of vasoactive hormones synthesis with a dominant rise of a vasoconstrictive hormones concentration.


Nematodes as Drivers of Plant Performance in Natural Systems.
Nematodes form an important part of soil biodiversity as the most abundant and functionally diverse animals affecting plant performance. Most studies on plant-nematode interactions are focused on agriculture, while plant-nematode interactions in nature are less known. Here we highlight that nematodes can contribute to vegetation dynamics through direct negative effects on plants, and indirect positive effects through top-down predation on plant-associated organisms. Global change alters these interactions, of which better understanding is rapidly needed to better predict functional consequences. By expanding the knowledge of plant-nematode interactions in natural systems, an increase in basic understanding of key ecological topics such as plant-soil interactions and plant invasion dynamics will be obtained, while also increasing the insights and potential biotic repertoire to be applicable in sustainable plant management.


Purification and characterization of uridine and thymidine phosphorylase from Lactobacillus casei.
Uridine and thymidine phosphorylases have been purified to homogeneity from crude extracts of Lactobacillus casei. Both enzymes had an apparent molecular mass of about 80 kDa. Uridine phosphorylase consisted of four identical subunits while thymidine phosphorylase was composed of two identical ones. The sequence of 23 amino-acid residues from its N-terminal end was analyzed. Uridine phosphorylase had a Km of 5.0 x 10(-3) M for uridine and 1.24 x 10(-1) M for phosphate, while thymidine phosphorylase had a Km of 1.32 x 10(-1) M for thymidine and 1.0 x 10(-1) M for phosphate. Uridine phosphorylase was equally active with uridine and 5-methyluridine, but had a low activity towards thymidine. Its activity was inhibited competitively by 3-O-methyl-alpha D-glucopyranoside, on the other hand thymidine phosphorylase activity was not affected by this compound. Thymidine phosphorylase showed specificity towards the deoxyribosyl moiety of the substrate. In addition, it required a nonsubstituted pyrimidine moiety or one which was substituted in position 5. The pattern of the double-reciprocal plots of the initial velocities vs. the concentrations of either one of the substrates, and the product inhibition kinetics, indicated that the catalytic mechanism of both enzymatic reactions is sequential rather than Ping-Pong and that the sequence of the addition of the substrates is random (rapid equilibrium). In the case of the uridine phosphorylase-catalyzed reaction, the products are also released randomly, while in the thymidine phosphorylase-catalyzed reaction deoxyribose 1-phosphate is released after thymine.


Neural responses in rat brain during acute immobilization stress: a [F-18]FDG micro PET imaging study.
We used the [F-18]FDG micro PET neuroimaging technique to investigate changes in brain activity induced by acute stress in rats. Animals were given immobilization stress for 1 or 2 h, or 1-h stress followed by 1-h recovery, after which their brains were scanned. Plasma corticosterone levels measured at various time points in separate groups of rats showed a rapid increase during stress and slower decrease after termination of the stress. Immobilization stress given for an hour activated the hypothalamus, entorhinal and insular/piriform cortices, and raphe pallidus nucleus. At the same time, the dorsal hippocampus, thalamus, other cortical areas (motor, somatosensory and barrel field), striatum, superior colliculus and cerebellum were deactivated. With 2-h immobilization stress, the activity of the hypothalamus, various cortical areas and dorsal hippocampus habituated during the second hour while that of the thalamus and cerebellum did not. During 1-h recovery, the hypothalamic activation and widespread cortical deactivation disappeared, but the dorsal hippocampus, thalamus and cerebellum still remained significantly deactivated. Additional brain areas such as the septum and prelimbic cortex now showed deactivation during recovery. Changes in glucose metabolism in the dorsal hippocampus and hypothalamus exhibited a highly significant negative correlation, supporting the view that the hippocampus is involved in regulating the stress response of the hypothalamo-pituitary-adrenal axis. The advantages and limitations of the [F-18]FDG micro PET used in this study are discussed.


Enterokinase induces severe necrosis and rapid mortality in cerulein pancreatitis: characterization of a novel noninvasive rat model of necro-hemorrhagic pancreatitis.
Unlike edematous pancreatitis, induction of severe necrotizing pancreatitis in rats generally requires an invasive laparotomy with infusion and/or ligation of the pancreatic duct or duodenal or arterial occlusion. The aim of this study was to establish and characterize a noninvasive model of severe acute pancreatitis in rats. Wistar rats were infused intravenously with cerulein or a combination of cerulein and enterokinase. Saline (154-mmol/L NaCl) or enterokinase only was infused in controls. In a first set of experiments, intrapancreatic protease activation and the release of cytokines were correlated with the severity of organ injury. Pancreatic and pulmonary injuries were determined at 6 h. In a second set of experiments, we assessed 24-h survival, serum parameters possibly reflecting the course of the disease, and morphologic changes later in the course of the disease. The severity of pancreatic injury and survival were correlated strongly with the amount of enterokinase infused simultaneously with cerulein. Trypsin as well as elastase and cathepsin B activity in pancreatic tissue samples were increased markedly in these animals. Marked pancreatic hemorrhage, necrosis, and leukocyte infiltration were present in animals with the greatest amounts of enterokinase infused. IL-6 and LDH, but not IL-1beta, CRP, and amylase, in serum correlated with the severity of pancreatitis. This noninvasive rat model of acute pancreatitis is characterized by major pancreatic necrosis, hemorrhage, and fatality. The simple and noninvasive induction technique may have advantages for future studies on inflammatory changes and sepsis in necrotizing pancreatitis compared with other currently available invasive models.


[Genetic diversity analysis of Paris by RSAP makers].
Studies on DNA fingerprinting of eight species of Paris and application of restriction site amplification polymorphism (RSAP) to the identification of Paris. Sequence-related amplified polymorphism (SRAP) molecular markers were used to detect the genetic diversity of 7 accessions of Paris collected from Tianquan and Baoxing in Sichuan, and one from Lijiang in Yunnan. The DNA fingerprinting of 8 species were generated by 18 primer combination screened from 45 primer combinations. Eight accessions were clustered into 4 groups by genetic distance. Based on molecular biology methods of RSAP analysis, accurate molecular identification could be performed on traditional Chinese medicinal material plants in Paris, and provided molecular evidence for taxonomy and identification of different species in Paris.


Participatory evaluations of trachoma control programmes in eight countries.
Trachoma is a major cause of blindness. The objective of this initiative was to conduct participatory process evaluations of the trachoma control programmes receiving support from the International Trachoma Initiative in eight countries. During each 2- to 4-week evaluation we analysed information collected at the central, district and community level through interviews, focus groups, questionnaires, direct observation of trachoma control activities, and existing data. Mapping and assessment of disease prevalence had been completed in four of eight countries. Integration of trachoma control activities into national planning and district-level service provision varied. Intersectoral partnerships to implement the SAFE strategy (i.e. surgery, antibiotics, facial cleanliness and environmental change) were well established in a few countries. In all eight countries, the number of surgeries performed annually was insufficient; and quality of surgery was rarely monitored. Mass distribution of antibiotics was carried out well in extremely resource-poor settings and good coverage was achieved, although the strategy for antibiotic distribution varied. Inadequate water and sanitation remained a major problem in all programme areas. Monitoring of programme activities was generally inadequate. The Morocco programme is an example from which lessons and processes can be learnt and adapted to other programme countries. Significant achievements have been made in implementing the SAFE strategy. Scaling up of activities to true national coverage should be planned and implemented provided the resources can be made available. Further standardization of how to assess, implement and monitor trachoma control activities will facilitate expansion of the programme.


Overestimation of on-road driving performance is associated with reduced driving safety in older drivers.
Older drivers often show less precise self-ratings with a tendency to overestimate themselves. It is unclear, however, how overestimators differ from underestimators or drivers with adequate self-ratings. 59 healthy older drivers participated in this on-road study. Besides standardized on-road driving assessment, the study protocol included the collection of neuropsychological and driving-related data as well as different self-ratings. Statistical analyses involved correlations between different subjective and objective ratings as well as statistical comparisons between drivers who overestimated and drivers who adequately rated their on-road driving performance (no drivers underestimated their performance). Despite positive correlations between different self- and expert ratings, our results revealed that 25 % of the participants overestimated their on-road driving skills. Among other things, overestimators showed poorer on-road driving performances, more prospective near and minor at-fault accidents, poorer cognitive performances in specific driving-related domains and reduced annual mileage. Our results suggest that older drivers who overestimate their driving skills show poorer performances within a broad range of skills that directly reflect or are closely related to driving safety. Against the background that an adequate self-assessment is required by German traffic regulations, our findings suggest that overestimators represent a risk group among the population of older drivers.


Risk Factors for Recurrent Staphylococcus aureus Bacteremia.
To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB). All SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE). PFGE-indistinguishable pairs from 40 patients underwent whole genome sequencing (WGS). Acute phase plasma from R-SAB and S-SAB patients was matched 1:1 for age, race, sex, and bacterial genotype, and underwent cytokine quantification using 25-analyte multiplex bead array. R-SAB occurred in 69 (9.1%) of the 756 study patients. Of the 69 patients, 30 experienced relapse (43.5%) and 39 reinfection (56.5%). Age, race, hemodialysis dependence, presence of foreign body, methicillin-resistant Staphyloccus aureus, and persistent bacteremia were individually associated with likelihood of recurrence. Multivariate risk modeling revealed that black hemodialysis patients were nearly 2 times more likely (odds ratio [OR] = 9.652 [95% confidence interval [CI], 5.402-17.418]) than white hemodialysis patients (OR = 4.53 [95% CI, 1.696-10.879]) to experience R-SAB. WGS confirmed PFGE interpretations in all cases. Median RANTES (regulated on activation, normal T cell expressed and secreted) levels in acute phase plasma from the initial episode of SAB were higher in R-SAB than in matched S-SAB controls (P = .0053, false discovery rate < 0.10). This study identified several risk factors for R-SAB. The largest risk for R-SAB is among black hemodialysis patients. Higher RANTES levels in R-SAB compared to matched controls warrants further study.


4-Hydroxynonenal activates Src through a non-canonical pathway that involves EGFR/PTP1B.
Src, a non-receptor protein tyrosine kinase involved in many biological processes, can be activated through both redox-dependent and independent mechanisms. 4-Hydroxy-2-nonenal (HNE) is a lipid peroxidation product that is increased in pathophysiological conditions associated with Src activation. This study examined how HNE activates human c-Src. In the canonical pathway Src activation is initiated by dephosphorylation of pTyr530 followed by conformational change that causes Src auto-phosphorylation at Tyr419 and its activation. HNE increased Src activation in both dose- and time-dependent manner, while it also increased Src phosphorylation at Tyr530 (pTyr530 Src), suggesting that HNE activated Src via a non-canonical mechanism. Protein tyrosine phosphatase 1B inhibitor (539741), at concentrations that increased basal pTyr530 Src, also increased basal Src activity and significantly reduced HNE-mediated Src activation. The EGFR inhibitor, AG1478, and EGFR silencing, abrogated HNE-mediated EGFR activation and inhibited basal and HNE-induced Src activity. In addition, AG1478 also eliminated the increase of basal Src activation by a PTP1B inhibitor. Taken together these data suggest that HNE can activate Src partly through a non-canonical pathway involving activation of EGFR and inhibition of PTP1B.


Biochemical studies of the late infantile form of metachromatic leukodystrophy.
Biochemical studies from a patient with the late infantile form of metachromatic leukodystrophy are presented. Since the autopsy was performed soon after death, viable cells were isolated from brain. The purified cells had altered densities and unusual appearances. The cells when placed in culture were able to incorporate radiolabeled substrates into cerebrosides, indicating that some of the cells were of oligodendroglial origin. Myelin was isolated using several different methods, and the degree of abnormality appeared to be dependent upon the method of isolation. Nonetheless, MLD myelin, while still retaining its characteristic-morphology, had increased levels of sulfatides (two to four times that normally found). Other membrane subfractions were isolated that were not present in control tissue and that were more abnormal in composition than myelin. Finally, the glycoproteins in MLD tissue also appeared to be altered. There were losses in MLD myelin glycoproteins that bind to Concanavalin A (Con A) and additional prominent glycoproteins that bind to wheat germ agglutinin.


Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism.
CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT). During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples. DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3. Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge.


Effect of different polishing systems on the surface roughness of nano-hybrid composites.
The study aimed to investigate the influence of different polishing systems on the surface roughness of nano-hybrid composite resins. Different shapes of polishing systems are available according to the site of work. To minimize variability, a new system with single shape is developed that can be utilized in both anterior as well as posterior teeth. Seventy composite discs were fabricated using Teflon well (10 mm × 3 mm). Two main group of nano-hybrid composite Group I - Filtek Z350 and Group II - Tetric N-Ceram were used (n = 35 for each group). Both groups were further divided into four subgroups. Subgroup a - OneGloss (n = 10), Subgroup b - PoGo (n = 10), Subgroup c - Sof-Lex spiral (n = 10), Subgroup d - Mylar strip (control, n = 5). Samples were polished according to the manufacturer's recommendations. Surface roughness test was performed using contact profilometer. The obtained data were analyzed using the one-way analysis of variance test. Tetric N-Ceram produced smoother surfaces than Filtek Z350 (P < 0.05). Mylar strip and "PoGo" created equally smooth surfaces, while significantly rougher surfaces were obtained after applications of "Sof-Lex spiral" and "OneGloss" (P < 0.05). Polishing ability of Tetric N-Ceram is better than Filtek Z350 XT. "PoGo" seems to be a better polishing system than "OneGloss" and "Sof-Lex Spiral."


Frequent activation of the β-catenin gene in sporadic colorectal carcinomas: A mutational & expression analysis.
β-catenin (CTNNB1), an oncogene/onco-protein and an adhesion molecule is a key effector in colorectal cancer (CRC). Its activation, and subsequent up-regulation of Wnt-signaling, is an important event in the development of certain human cancers including CRC. Mutations in the β-catenin gene in the region of serine-threonine glycogen kinase (GSK)-3β phosphorylation target sites have been identified in colorectal cancer in humans. In the current study, we investigated 60 sporadic colorectal adenocarcinomas along with adjoining and normal mucosa cases in humans for β-catenin mutations. Thirteen of sixty colorectal tumors from humans had point mutations with a frequency of 21.66% at codons 24, 26, 27, 32, 34, 35, 41, 42,43, 46, 49, 54, 55, or 67 sites which are mutated in colorectal cancer and some of these sites in other cancers. Thus, there appears to be a key involvement of β-catenin activation in human colorectal carcinogenesis. mRNA expression analysis using q-Real Time PCR showed 21.5-fold up-regulation of β-catenin mRNA in tumor tissue compared to normal and adjoining mucosa. Protein expression analysis using immunohistochemistry, confocal microscopy, and Western blot confirmed aberrant accumulation of β-catenin protein along the nucleus and cytoplasm following mutation. The observed mutations and up-regulation of mRNA in tumors, and the increased expression of β-catenin protein in CRC suggest that these alterations are early and prognostic events in sporadic colorectal carcinogenesis in humans. © 2015 Wiley Periodicals, Inc.


Fine needle aspiration cytology of granulomatous prostatitis induced by BCG immunotherapy of bladder cancer.
Six patients treated with intravesical bacillus Calmette-Guérin (BCG) for superficial bladder cancer had granulomatous prostatitis demonstrated histologically by transperineal needle biopsy. Four of the six patients also underwent transrectal fine needle aspiration (FNA) for cytologic study. The diagnosis of granulomatous prostatitis was made cytologically in all four without knowledge of the histologic findings. Granulomatous prostatitis appears to be common following intravesical BCG treatment; these cases show that FNA cytology can be recommended as a method for diagnosing this complication.


The study of feasibility and acceptability of using HIV self-tests in high-risk Iranian populations (FSWs, MSM, and TGs): a cross-sectional study.
This study aimed to evaluate the feasibility of using the HIV self-test in high-risk Iranian groups (MSM, FSWs, and TGs). This study was a mixed study designed as a quantitative-qualitative study conducted between October 1, 2020, and June 22, 2021, in Tehran and Karaj, Iran. The sample size needed for this study generally was 1000 people, including FSWs, MSM, and transgender individuals. Convenience and snowball sampling methods were used to collect the samples. A total of 930 eligible respondents were enrolled in the study, of whom 456 (49%) were female and 49 (5.3%) were transgender (98% of TGs were male to female), and their mean age was 33.63 years (10.54 SD). The feasibility of using HIV self-tests in Iranian high-risk groups was significantly high. The majority of participants (97%) did not have any confidentiality problems while preparing or performing the test. In general, feasibility was assessed based on five questions. The overall feasibility score was 6.33 (0.824 SD). Taking tests, reading HIV test results, finding a safe place to do the test, and accessing HIV self-tests showed a high average. HIV self-testing was highly acceptable and feasible among high-risk populations, so routine HIV testing was efficiently possible.


[Investigations on the relationship between intraocular pressure and perifoveal capillary circulation in glaucoma patients using the entoptic blood corpuscle phenomenon (author's transl)].
Blood circulation in the central retina was examined in 30 eyes suffering from glaucoma, using the entoptic phenomenon to count leucocytes travelling through the retinal capillaries in the macula area. Two measurements were taken for each eye at different intraocular pressure levels and the results were compared with each other. They showed that reduction of an originally high intraocular tension level significantly increased the blood flow. In a control group of healthy eyes in a similar group of patients insignificant changes in blood flow were recorded. There was thus a direct linear relationship between reduction of intraocular pressure and relative increase in blood flow with a strongly positive correlation (r = 0,74). Hence an effective autoregulation of blood flow in relation to changes in intraocular pressure could not be demonstrated.


Measurement of multidrug-resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance.
We measured the levels of messenger RNA of the human multidrug-resistance gene (MDR1) in 25 urogenital tumors before chemotherapy. Many of the renal cell carcinomas continued to express MDR1 gene at high levels, reflecting the increased expression of MDR1 RNA in normal kidneys. In other urogenital tumors, the MDR1 RNA levels were low reflecting low MDR1 RNA levels in normal bladder, prostate and testis. For comparative purposes, we performed in vitro chemosensitivity testing on many tumor samples using soft agar culture techniques. Vinblastine sensitivity in vitro inversely correlated with MDR1 RNA levels (p less than 0.01). Moreover, mean sensitivity of seven renal cell carcinomas to vinblastin was significantly lower than that of the other seven cancers (p less than 0.05). As for doxorubicin, mean sensitivity of six renal cell carcinomas was lower than the others (p less than 0.1). These results suggest that the high MDR1 RNA levels in renal cell carcinomas are associated with intrinsic multidrug-resistance.


Melanocyte stimulating hormone induces the differentiation of mouse epidermal melanocytes in serum-free culture.
In serum-free primary culture of dissociated mouse epidermal cells, alpha-melanocyte stimulating hormone (alpha-MSH) and dibutyryl cyclic AMP (DBcAMP) induced the differentiation of melanocytes. Moreover, the proliferation of melanocytes was also induced in the dishes cultured with DBcAMP, but not with alpha-MSH. In order to clarify the role of keratinocytes in melanocyte proliferation and differentiation, pure cultures of keratinocytes were established in serum-free medium. Subconfluent primary keratinocytes were trypsinized and seeded into pure primary melanoblasts cultured with serum-free medium that did not contain alpha-MSH or DBcAMP. Melanoblasts were cultured with alpha-MSH or DBcAMP in the presence or absence of keratinocytes. alpha-MSH failed to induce melanocyte differentiation in the absence of keratinocytes. DBcAMP failed to induce melanocyte proliferation in the absence of keratinocytes, although it induced melanocyte differentiation even in the absence of keratinocytes. These results suggest that keratinocyte-derived factors are required not only for the induction of melanocyte differentiation by alpha-MSH but also for the induction of melanocyte proliferation by DBcAMP.


Graft Replacement of Kommerell Diverticulum and In Situ Aberrant Subclavian Artery Reconstruction.
This study aimed to evaluate the early and long-term outcomes of graft replacement of Kommerell diverticulum and in situ reconstruction of aberrant subclavian arteries in adults. Seventeen patients, 6 symptomatic and 11 with right aortic arch, underwent open repair of Kommerell diverticulum from October 1999 to September 2017. Two of these patients underwent open surgical treatment of a ruptured aneurysm. Surgical indications were dilatation of Kommerell aneurysm (n = 9), the presence of a nondissecting aneurysm with Kommerell diverticulum (n = 6), acute type A aortic dissection (n = 1), and complicated acute type B aortic dissection (n = 1). Ten patients underwent total arch replacement and descending aorta replacement through a thoracotomy. Five patients underwent arch replacement and in situ reconstruction through a median sternotomy. All patients except 1 also underwent in situ reconstruction of their aberrant subclavian artery. In-hospital death occurred in 1 patient (5.9%), who underwent total arch replacement for a ruptured aneurysm. Permanent neurologic deficit did not occur in any patient, whereas transient neurologic deficit occurred in 2 patients (11.8%). Five- and 10-year survival rates were 85.2 ± 9.8% and 75.8 ± 12.5%, respectively. There was no symptom recurrence or stenosis of the reconstructed subclavian arteries. Early outcomes of graft replacement of Kommerell diverticulum and in situ aberrant subclavian artery reconstruction were acceptable. As for long-term outcomes, symptomatic improvement and an excellent patency rate among reconstructed aberrant subclavian arteries suggest that in situ surgical repair is an effective treatment option.


Radiation therapy for stage I and IIA testicular seminoma.
To review the survival, cure rate, treatment morbidity, and late sequelae of histologically confirmed seminoma patients who underwent orchiectomy and radiation therapy at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, from 1964 to 1988. There were 128 patients, with a median patient age of 37 years (range, 17-79 years). Follow-up ranged from 1-24 years, with a median of 6.7 years. There were 95 patients with Stage I and 33 with Stage IIA disease. All patients were treated with orchiectomy followed by iliac and paraaortic irradiation (median tumor dose: 2500 cGy for Stage I and 3400 cGy for Stage IIA patients). Twenty-five of 33 patients with Stage IIA disease received prophylactic mediastinal and left supraclavicular irradiation (median dose, 2700 cGy). For patients with Stage I disease, 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 97%, 100%, and 100%, respectively. For patients with Stage IIA disease, the 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 93%, 89%, and 97%, respectively. Four patients (3%) had recurrences; all were outside the radiation treatment field. Three of four were successfully salvaged with chemotherapy and rendered disease-free; the other patient refused treatment. There were no mediastinal recurrences whether prophylactic mediastinal irradiation was administered or not. Bowel obstruction and necrosis developed in one patient who received 3363 cGy midplane dose to the pelvic and paraaortic areas as well as additional intraperitoneal colloidal 198Au (150 mCi) for a ruptured seminoma from an undescended testis. In summary, radical orchiectomy and irradiation of the iliac and paraaortic lymphatics is the treatment of choice for patients with Stage I and IIA testicular seminoma.


Home monitoring of warfarin therapy in children with a whole blood prothrombin time monitor.
We prospectively evaluated a capillary whole blood prothrombin time (PT) monitor (Biotrack, Ciba Corning) in an outpatient pediatric anticoagulation clinic (40 clinic patients) and in age-matched healthy subjects (30 control subjects). Subsequently, 23 children requiring warfarin therapy were placed on a home program (home patients) using the PT monitor; their parents were trained and the results followed by clinic staff. The PT results were reported as internationalized normalized ratios (INRs). The laboratory and PT-monitor INR values were similar for the clinic patients and the control subjects (y = 0.76x + 0.38; r = 0.93; p < 0.001). The accuracy of the PT monitor (the difference between INR values and the laboratory INR) was best at an INR of 2.5 to 3.5; 90% of paired INR values were within 0.8 INR units. The average duration of monitoring for home patients was 13 months (range, 2 to 60 months). They had an average of 3 dose measurements (range, 1 to 11 measurements) and 1.8 dose changes (range, 0.6 to 4.5 changes) per month. Of the 599 measurements, 63% were within the therapeutic range, similar to those for clinic patients; the dose requirements were also similar. There was 1 significant bleeding event, a subdural hematoma in a patient with an INR of 4.1, and 1 catheter-related thrombotic event with an INR of 1.2; both children recovered. Of the 23 families, one discontinued home monitoring because of parental discomfort, 2 children died of their primary disease, 6 completed warfarin therapy, and 14 remain on the home program. We conclude that the whole blood PT/INR monitor is safe and offers practical advantages to children requiring anticoagulation.


Molecular Targets in the Chemotherapy of Coronavirus Infection.
In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. In the second stage, when the multiplication of the virus decreases and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia, and secondary bacterial pneumonia and sepsis events develop, a pathogenetic therapeutic approach including extracorporeal blood oxygenation, detoxification, and anti-inflammatory and anti-bacterial therapy seems to be the most effective way for the patient's recovery.


DetoxiProt: an integrated database for detoxification proteins.
Detoxification proteins are a class of proteins for degradation and/or elimination of endogenous and exogenous toxins or medicines, as well as reactive oxygen species (ROS) produced by these materials. Most of these proteins are generated as a response to the stimulation of toxins or medicines. They are essential for the clearance of harmful substances and for maintenance of physiological balance in organisms. Thus, it is important to collect and integrate information on detoxification proteins. To store, retrieve and analyze the information related to their features and functions, we developed the DetoxiProt, a comprehensive database for annotation of these proteins. This database provides detailed introductions about different classes of the detoxification proteins. Extensive annotations of these proteins, including sequences, structures, features, inducers, inhibitors, substrates, chromosomal location, functional domains as well as physiological-biochemical properties were generated. Furthermore, pre-computed BLAST results, multiple sequence alignments and evolutionary trees for detoxification proteins are also provided for evolutionary study of conserved function and pathways. The current version of DetoxiProt contains 5956 protein entries distributed in 628 organisms. An easy to use web interface was designed, so that annotations about each detoxification protein can be retrieved by browsing with a specific method or by searching with different criteria. DetoxiProt provides an effective and efficient way of accessing the detoxification protein sequences and other high-quality information. This database would be a valuable source for toxicologists, pharmacologists and medicinal chemists. DetoxiProt database is freely available at http://lifecenter.sgst.cn/detoxiprot/.


Comparing Hemodynamic Responses to Diazepam, Propofol and Etomidate During Anesthesia Induction in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Graft Surgery: a Double-blind, Randomized Clinical Trial.
Anesthesia induction is often accompanied by a period of hemodynamic instability, which could be deleterious in patients with coronary artery disease (CAD) and left ventricular dysfunction undergoing coronary artery bypass graft (CABG) surgery. The aim of this study was to compare the hemodynamic responses to propofol, etomidate, and diazepam following anesthesia induction, laryngoscopy and intubation in CABG surgery patients with low ejection fraction (EF). A double-blind randomized, clinical study was performed on 150 patients with CAD and left ventricular dysfunction (EF≤35%) scheduled for elective CABG surgery with Cardiopulmonary bypass (CPB). Patients were randomly allocated to three groups A, B, and C. These patients received propofol, etomidate or diazepam at induction of anesthesia, respectively. Hemodynamic variables (systolic and diastolic blood pressure [SBP, DBP], mean arterial pressure [MAP] and heart rate [HR]) were measured and recorded at baseline, immediately before laryngoscopy and tracheal intubation and one and three minutes after intubation. One minute after induction and before laryngoscopy, there was a statistically significant decrease from the baseline in SBP, DBP and MAP in all three groups, but these variables in each hemodynamic parameters in diazepam group were less than other two groups (p<0.001). Moreover, the mean HR decreased in patients receiving propofol and etomidate one minute after induction and before laryngoscopy, but did not decreased in the diazepam group (p=0.005). The present study showed that in patients undergoing CABG surgery with low EF, diazepam is more favorable in terms of hemodynamic stability compared to propofol and etomidate and this drug can be used safely for induction of anesthesia in patients with impaired ventricular function.


Use of continuous lactose fermentation for ethanol production by Kluveromyces marxianus for verification and extension of a biochemically structured model.
A biochemically structured model has been developed to describe the continuous fermentation of lactose to ethanol by Kluveromyces marxianus and allowed metabolic coefficients to be determined. Anaerobic lactose-limited chemostat fermentations at different dilution rates (0.02-0.35h(-1)) were performed. Species specific rates of consumption/formation, as well as yield coefficients were determined. Ethanol yield (0.655 C-mol ethanol(∗)C-mol lactose(-1)) was as high as 98% of theoretical. The modeling procedure allowed calculation of maintenance coefficients for lactose consumption and ethanol production of m(s)=0.6029 and m(e)=0.4218 (C-mol) and (C-molh)(-1), respectively. True yield coefficients for biomass, ethanol and glycerol production were calculated to be Y(true)(sx)=0.114, Y(true)(ex)=0.192 and Y(sg)=2.250 (C-mol) and (C-mol)(-1), respectively. Model calculated maintenance and true yield coefficients agreed very closely with those determined by regressions of the experimental data. The model developed provides a solid basis for the rational design of optimised fermentation of cheese whey.


A Canadian perspective on the revised 2020 ASHP-IDSA-PIDS-SIDP guidelines for vancomycin AUC-based therapeutic drug monitoring for serious MRSA infections.
A revised consensus guideline on therapeutic drug monitoring (TDM) of vancomycin for serious methicillin-resistant Staphylococcus aureus (MRSA) infections was recently published with endorsement of numerous American pharmacy and medical societies. Changing practice from trough TDM to area-under-the-curve-(AUC)-guided dosing was suggested. Recent literature was critically appraised to determine whether AUC TDM is appropriate for Canadian hospital practice. Previous 2009 vancomycin consensus guidelines recommended trough levels of 15-20 mg/L for serious MRSA infections, based on relatively poor evidence for efficacy or safety. In the past decade, aggressive trough targets have led to unnecessary toxicity. Adoption of a TDM strategy using an alternative parameter (AUC) has been suggested, although the evidence for any outcome benefits is low quality. In addition, implementation would require greater resources at health care institutions in the forms of more frequent serum levels or acquisition of costly Bayesian software programs. Most studies on this subject have been observational and retrospective; therefore, relationships between TDM parameters and outcomes have not been convincingly and consistently demonstrated to be causal in nature. Despite claims to the contrary, based on few in silico experiments, available clinical data suggest correlation of trough levels and AUC is high. TDM with lower target trough levels is a simpler solution to reduce risk of toxicity. There are serious concerns with adoption of AUC TDM of vancomycin into routine practice in Canada. Trough-based monitoring with modest reduction in target levels remains the most evidence-informed practice at this time.


Caregiver engagement interventions on reducing the anxiety and depression of children with chronic health conditions and their caregivers: A meta-analysis of randomized controlled trials.
Anxiety and depression are common debilitating mental health issues in families of children with chronic health conditions. It is essential to consider the mediating role of caregivers between children and healthcare workers. Previous research has evaluated the effectiveness of caregiver engagement interventions in reducing anxiety and depression in chronically ill children and their caregivers, but their overall impact awaits a synthesis of the available evidence. We performed a comprehensive search using PubMed, Embase, Web of Science, Cochrane Library, Ovid, PsycINFO, APA PsycArticles, and Cumulative Index of Nursing and Allied Health Literature (CINAHL). Twenty-nine studies were included. The results demonstrated that caregiver engagement interventions significantly decreased anxiety (standardized mean difference [SMD] = -0.49; 95% confidence interval [CI], -0.77 to -0.22; P < 0.001) and depression (SMD = -0.37; 95% CI, -0.55 to -0.18; P < 0.001) among caregivers, particularly in developing countries. However, no improvements in the anxiety (SMD = 0.00; 95% CI, -0.46 to 0.46; P = 0.99) and depression (SMD = -0.14; 95% CI, -0.32 to 0.04; P = 0.14) of children were observed. Significant evidence exists regarding the positive effects of caregiver engagement interventions on caregivers' anxiety and depression. Further recommendations for future research should focus on engagement interventions that reduce the anxiety and depression for children with chronic conditions. Clinicians should concentrate on the mental health of chronically ill children and their caregivers and extend caregiver engagement therapies to improve anxiety and depression resulting from managing the disease.


A Hierarchical Model for Accuracy and Choice on Standardized Tests.
This paper assesses the psychometric value of allowing test-takers choice in standardized testing. New theoretical results examine the conditions where allowing choice improves score precision. A hierarchical framework is presented for jointly modeling the accuracy of cognitive responses and item choices. The statistical methodology is disseminated in the 'cIRT' R package. An 'answer two, choose one' (A2C1) test administration design is introduced to avoid challenges associated with nonignorable missing data. Experimental results suggest that the A2C1 design and payout structure encouraged subjects to choose items consistent with their cognitive trait levels. Substantively, the experimental data suggest that item choices yielded comparable information and discrimination ability as cognitive items. Given there are no clear guidelines for writing more or less discriminating items, one practical implication is that choice can serve as a mechanism to improve score precision.


Comparison of Laparoscopic Discoid Resection and Segmental Resection for Colorectal Endometriosis Using a Propensity Score Matching Analysis.
Our primary endpoint was to compare the intra- and postoperative complications, whereas secondary endpoints were the occurrence of voiding dysfunction and evaluation of the quality or life of segmental and discoid resection in patients with colorectal endometriosis. Retrospective study (Canadian Task Force classification II-2). Tenon University Hospital in Paris. Thirty-one 31 patients who underwent a conservative surgery and 31 patients who underwent. The 2 groups were compared using propensity score matching (PSM) analysis, with a median follow-up of 247 days (8.2 months). Discoid colorectal resection was associated with a shorter operating time (155 vs 180 minutes, p = .03) and hospital stay (7 vs 8 days, p = .002) than segmental colorectal resection; however, a similar intra- and postoperative complication rate was found. A higher rate of postoperative voiding dysfunction was observed in the segmental resection group (19% vs 45%, p = .03) as well as duration of voiding dysfunction requiring bladder self-catheterization longer than 30 days (0 vs 22%, p = .005). Our PSM analysis suggests the advantages of discoid resection because it results in a similar surgical complication rate to segmental resection but with advantages in operating time, hospital stay, and voiding dysfunction.


Lipid-associated rheumatologic syndromes.
Rheumatologic manifestations of hyperlipidemia and lipid-associated arthritis are rarely seen in the rheumatologist's office. On the other hand, a rheumatologist may be the clinician who identifies and initiates proper therapy for disorders related to hyperlipidemia when the musculoskeletal manifestations of these syndromes are recognized. In this article both the joint and tendon manifestations are reviewed, including the lesser known lipid liquid crystal form of arthritis. The relationship between gout and hyperuricemia is briefly discussed, as are the autoimmune manifestations of lipid-lowering therapy.


Single and combined effects of amino polystyrene and perfluorooctane sulfonate on hydrogen-producing thermophilic bacteria and the interaction mechanisms.
As a carrier of perfluorooctane sulfonate, nano-plastics are ubiquitous and finally enriched in the sludge, which is widely used as a raw material for the production of bioenergy (hydrogen or methane) by anaerobic digestion. However, there are still many unknowns about their metabolic toxicity to functional microbes (e.g. hydrogen-producing thermophilic bacteria). Therefore, single and combined effects of amino polystyrene (NPS: 70 nm; 0.2 mg/L) and perfluorooctane sulfonate (PFOS: 0.1, 1 and 5 mg/L) on hydrogen-producing thermophilic bacteria were investigated after exposure for 7 days at 55 °C and pH = 5.7. Single NPS exhibited obvious interference to the metabolism of thermophilic bacteria, resulting in a 53.9% reduction in hydrogen production. However, the combined NPS + PFOS produced an antagonistic effect, leading to a 31.6% reduction in hydrogen production. Nonetheless, the single and combined exposure did not alter the type of hydrogen production (acetic acid-type hydrogen fermentation). Moreover, single NPS and combined NPS + PFOS not only induced the changes of the composition of extracellular polymers (EPSs) and π bond structure of the protein in EPSs, but also decreased the activity of hydrolase in EPSs and surface charge of EPSs. Compared to single NPS exposure, NPS + PFOS-exposed thermophilic bacteria was less permeable to a semi-membrane permeable dye and produced less reactive oxygen species, but were still significantly higher than control group. In short, the main mechanisms of single NPS and combined NPS + PFOS were both to increase cell permeability and to induce oxidative stress. The addition of PFOS alleviated the toxic effect of NPS, but did not change its mechanism of toxicity.


Editorial: Neurobiological Substrates of Subclinical Obsessive-Compulsive Disorder in Children.
"I'm a little bit OCD" is a common refrain on social media, usually referring to a benign tendency toward cleanliness, order, and "keeping one's eye on the prize." In truth, obsessive-compulsive disorder (OCD) is a debilitating disorder of ritual and doubt that carries a significant burden on functioning for those affected. Even subclinical OCD, which is 2-8 times more common than OCD in children, can engender considerable suffering, including social withdrawal, anxiety, depressed mood, and excess somatic complaints.1,2 It has been suggested that subclinical OCD symptoms during childhood may be precursors to developing the full disorder in adolescence and adulthood. However, the neurobiological underpinnings of subclinical OCD and their development and correlation to child functioning have not yet been well elucidated.


The economics of eHealth and mHealth.
While mHealth has the potential to overcome traditional obstacles to the delivery of health services to the poor in lower and middle-income countries--issues related to access, quality, time, and resources--there is little evidence as to whether the expected benefits and savings can be actualized on a large scale. As a first step to developing the investment case for mHealth, this article outlines some of the key economic and financial questions that need to be answered in developing in-country eHealth investments. The proposed questions focus on the costs of eHealth infrastructure; regulatory structures that provide incentives at different levels of the health delivery system to encourage investment in, and use of, eHealth; and measuring the outcomes of successful eHealth utilization, including anticipated return on investment.


Younger age at stroke onset but not thrombolytic treatment predicts poststroke epilepsy: An updated meta-analysis.
Stroke is the most commonly identified cause of late-onset epilepsy. Risk factors for poststroke epilepsy (PSE) are partially elucidated, and many studies have been performed in recent years. We aimed to update our previous systematic review and meta-analysis on risk factors for PSE. PubMed, Google Scholar, and Scopus databases were searched. Articles published in English (1987-2019) were included. Odds ratios (OR) and mean values were calculated for examined variables. Thirty studies with different designs were included, enrolling 26,045 patients who experienced stroke, of whom 1800 had PSE, corresponding to a prevalence of 7%. Cortical lesions (OR: 3.58, 95% confidence interval (CI): 2.35-5.46, p < 0.001), hemorrhagic component (OR: 2.47, 95% CI: 1.68-3.64, p < 0.001), early seizures (ES) (OR: 4.88, 95% CI: 3.08-7.72, p < 0.001), and younger age at stroke onset (difference in means: 2.97 years, 95% CI: 0.78 to 5.16, p = 0.008) favor PSE. Sex and acute treatment with recombinant tissue plasminogen activator (rtPA) do not predict the occurrence of PSE. Despite limitations due to the uneven quality and design of the studies, the present meta-analysis confirms that cortical involvement, hemorrhagic component, and ES are associated with a higher risk of PSE. In this update, younger age at stroke onset but not thrombolytic treatment seems to increase the risk for PSE. This article is part of the Special Issue "Seizures & Stroke".


Lipid peroxidation in brain during aging in the senescence-accelerated mouse (SAM).
Accumulation of toxic amyloid-beta (Abeta)-peptide is suggested to cause oxidative stress in Alzheimer's disease (AD) brain, and decrease the content of polyunsaturated fatty acids (PUFA) in neuronal membrane lipids. The senescence accelerated prone mice (SAMP8) have age-related increases in the level of hippocampal Abeta-peptide, learning and memory deficits, and a shorter lifespan than their controls. The effects of age-related oxidative damage on PUFA content in membrane phospholipids (PL), and alpha-tocopherol concentration were investigated in hippocampus and amygdala of 2-, 4-, 12-, and 18-month-old SAMP8 mice. In comparison to the younger SAMP8 mice, the hippocampus of the 12-month-old mice contained lower proportions of docosahexaenoic acid (DHA) in phosphatidylserine (PS) and phosphatidylinositol (PI), and higher proportions of arachidonic acid (AA) in PS. Their amygdala contained a lower proportion of AA in phosphatidylcholine (PC). In the hippocampus of the oldest age group, the proportions of DHA in PS, and AA in PC and PI were higher than in the younger age groups. At 2 months of age, the amygdala contained a higher concentration of alpha-tocopherol than the hippocampus, but this difference between the two brain regions was lost with aging. The oldest age group contained the highest concentration of alpha-tocopherol, indicating a protection against oxidative damage of PUFA in brain membrane phospholipids.


X-ray, Cryo-EM, and computationally predicted protein structures used in integrative modeling of HIV Env glycoprotein gp120 in complex with CD4 and 17b.
We present the data used for an integrative approach to computational modeling of proteins with large variable domains, specifically applied in this context to model HIV Env glycoprotein gp120 in its CD4 and 17b bound state. The initial data involved X-ray structure PDBID:1GC1 and electron microscopy image EMD:5020. Other existing X-ray structures were used as controls to validate and hierarchically refine partial and complete computational models. A summary of the experiment protocol and data was published (Rasheed et al., 2015) [26], along with detailed analysis of the final model (PDBID:3J70) and its implications.


Multiscale, patient-specific computational fluid dynamics models predict formation of neointimal hyperplasia in saphenous vein grafts.
Stenosis due to neointimal hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers is insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics simulations of flow in the lumen and a biochemical model representing NIH growth mechanisms inside the vessel wall. For all three patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography scans.


Role of catecholamines in the development of tolerance to barbiturates and ethanol.
The destruction of noradrenergic systems in brain by administration of 6-hydroxydopamine prior to chronic ethanol treatment prevented the development of tolerance to ethanol. Animals pretreated with 6-hydroxy dopamine also showed no cross tolerance to barbiturates. Destruction of noradrenergic systems prior to chronic treatment with barbiturates also partially prevented the development of tolerance to pentobarbital. 6-Hydroxydopamine pretreatment had little effect on the signs of physical dependence produced by ethanol. The possible dissociation of tolerance and dependence and the role of noradrenergic systems in these phenomena is discussed.


Effect of treatment with an ivermectin sustained-release bolus on productivity of stocker beef calves.
Three groups of 30 crossbred beef steers, 8-10 months of age and ranging in weight from 158 to 320 kg, were used to compare effects of treatment with an ivermectin sustained-release bolus or two ivermectin injectable treatments on parasite control and productivity in relation to untreated controls during a 168 day winter-spring grazing period. Each group of 30 consisted of five cattle on each of six separate 1.6 ha pastures. Treatments on Day 0 (12 December) were: Group 1: untreated controls; Group 2: ivermectin injectable at 200 micrograms kg-1 bodyweight, s.c., on Day 0 and Day 56; Group 3: ivermectin sustained-release bolus to deliver ivermectin at 12 mg day-1 over approximately 135 days. All cattle were weighed at 28 day intervals and fecal samples were collected for egg per gram counts (EPG). Geometric mean EPG for Group 3 remained consistently less than 1.0 after Day 0 and were highest (2.4) on Day 168. All group EPG were significantly different (P < 0.01) by Day 56, and EPG of Group 2 had increased to 10.5 following initial treatment and to 42.8 on Day 112. With the exception of a low mean EPG of 6.8 for Group 1 on Day 112, EPG of the group were consistently highest (range 24.9-36.0) to the end of the experiment. Ostertagia ostertagi was predominant, along with smaller proportions of Haemonchus placei and Cooperia spp. Throughout the experiment Group 3 had highest liveweights and gains that were most often different from those of Group 1 at P < 0.01 or greater.(ABSTRACT TRUNCATED AT 250 WORDS)