Association of Peripheral Blood Levels of Cytokines With Autism Spectrum Disorder: A Meta-Analysis.
Background: Although increasing evidence suggests an association between alterations in peripheral cytokines and autism spectrum disorder (ASD), a consensus is lacking. To determine whether abnormal cytokine profiles in peripheral blood were associated with ASD, we performed this systemic review and meta-analysis. Methods: A systematic literature search was conducted through the Embase, PubMed, Web of Knowledge, PsycINFO, and Cochrane databases up to 4 June 2020. Clinical studies exploring the aberration of peripheral cytokines of autistic patients and controls were included in our meta-analysis. We pooled extracted data using fixed- or random-effects models based on heterogeneity tests with Comprehensive Meta-analysis software. We converted standardized mean differences to Hedges' g statistic to obtain the effect sizes adjusted for sample size. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also carried out. Results: Sixty-one articles (326 studies) were included to assess the association between 76 cytokines and ASD. We conducted our meta-analysis based on 37 cytokines with 289 studies. Since there were fewer than three studies on any of the other 39 cytokines, we only provided basic information for them. The levels of peripheral IL-6, IL-1β, IL-12p70, macrophage migration inhibitory factor (MIF), eotaxin-1, monocyte chemotactic protein-1 (MCP-1), IL-8, IL-7, IL-2, IL-12, tumor necrosis factor-α (TNF-α), IL-17, and IL-4 were defined as abnormal cytokines in the peripheral blood of ASD patients compared with controls. The other 24 cytokines did not obviously change in ASD patients compared with the controls. Conclusions: The findings of our meta-analysis strengthen the evidence for an abnormal cytokine profile in ASD. These abnormal cytokines may be potential biomarkers for the diagnosis and treatment of ASD in the future.


Bidirectional reflectance of the moonlit Earth.
From OGO-4 airglow photometer data and computed lunar spectral irradiances at the subsatellite point, the highest radiance over clouds and lowest radiance over open ocean are examined near 3914 A, 5577 A, 5893 A, 6225 A, and 6300 A in terms of bidirectional reflectance. The results are compared to and are consistent with mathematical models of the atmosphere developed by Plass and Kattawar, and with daytime measurements from OSO-3 by Neel, Griffin, and Millard.


Retinoic acid plus arsenic trioxide, the ultimate panacea for acute promyelocytic leukemia?
Rarely in the field of cancer treatment did we experience as many surprises as with acute promyelocytic leukemia (APL). Yet, the latest clinical trial reported by Lo-Coco et al in the New England Journal of Medicine is a practice-changing study, as it reports a very favorable outcome of virtually all enrolled low-intermediate risk patients with APL without any DNA-damaging chemotherapy. Although predicted from previous small pilot studies, these elegant and stringently controlled results open a new era in leukemia therapy.


[Length of hospital stay due to DRG reimbursement].
The introduction of DRG systems causes a paradigm shift in consideration of length of hospital stay. A daily rate for a hospital bed is an inventive to lengthen hospital stay as long as possible. In a DRG system it would be lucrative to release a patient from hospital as soon as possible and tenable. If DRGs are calculated properly, based on a valid statistical analysis of average length of stay, hospital reimbursement will be ensured in the average of one year. Not cost-effective cases will be compensated with profitable patients. There is no economic need to release or transfer patients from hospital earlier than necessary or tenable. To have sufficient control over the economic situation in each individual patient it is necessary and recommended to build up a cost unit accounting.


Neural correlates of the perception for novel objects.
Perception of novel objects is of enormous importance in our lives. People have to perceive or understand novel objects when seeing an original painting, admiring an unconventional construction, and using an inventive device. However, very little is known about neural mechanisms underlying the perception for novel objects. Perception of novel objects relies on the integration of unusual features of novel objects in order to identify what such objects are. In the present study, functional Magnetic Resonance Imaging (MRI) was employed to investigate neural correlates of perception of novel objects. The neuroimaging data on participants engaged in novel object viewing versus ordinary object viewing revealed that perception of novel objects involves significant activation in the left precuneus (Brodmann area 7) and the right visual cortex. The results suggest that the left precuneus is associated with the integration of unusual features of novel objects, while the right visual cortex is sensitive to the detection of such features. Our findings highlight the left precuneus as a crucial component of the neural circuitry underlying perception of novel objects.


Silencing of the rotavirus NSP4 protein decreases the incidence of biliary atresia in murine model.
Biliary atresia is a common disease in neonates which causes obstructive jaundice and progressive hepatic fibrosis. Our previous studies indicate that rotavirus infection is an initiator in the pathogenesis of experimental biliary atresia (BA) through the induction of increased nuclear factor-kappaB and abnormal activation of the osteopontin inflammation pathway. In the setting of rotavirus infection, rotavirus nonstructural protein 4 (NSP4) serves as an important immunogen, viral protein 7 (VP7) is necessary in rotavirus maturity and viral protein 4 (VP4) is a virulence determiner. The purpose of the current study is to clarify the roles of NSP4, VP7 and VP4 in the pathogenesis of experimental BA. Primary cultured extrahepatic biliary epithelia were infected with Rotavirus (mmu18006). Small interfering RNA targeting NSP4, VP7 or VP4 was transfected before rotavirus infection both in vitro and in vivo. We analyzed the incidence of BA, morphological change, morphogenesis of viral particles and viral mRNA and protein expression. The in vitro experiments showed NSP4 silencing decreased the levels of VP7 and VP4, reduced viral particles and decreased cytopathic effect. NSP4-positive cells had strongly positive expression of integrin subunit α2. Silencing of VP7 or VP4 partially decreased epithelial injury. Animal experiments indicated after NSP4 silencing, mouse pups had lower incidence of BA than after VP7 or VP4 silencing. However, 33.3% of VP4-silenced pups (N = 6) suffered BA and 50% of pups (N = 6) suffered biliary injury after VP7 silencing. Hepatic injury was decreased after NSP4 or VP4 silencing. Neither VP4 nor VP7 were detected in the biliary ducts after NSP4. All together, NSP4 silencing down-regulates VP7 and VP4, resulting in decreased incidence of BA.


Activated phosphoinositide 3-dinase delta syndrome (APDS): An update.
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a recently described form of inborn error of immunity (IEI) caused by heterozygous mutations in PIK3CD or PIK3R1 genes, respectively, encoding leukocyte-restricted catalytic p110δ subunit and the ubiquitously expressed regulatory p85 α subunit of the phosphoinositide 3-kinase δ (PI3Kδ). The first described patients with respiratory infections, hypogammaglobulinemia with normal to elevated IgM serum levels, lymphopenia, and lymphoproliferation. Since the original description, it is becoming evident that the onset of disease may be somewhat variable over time, both in terms of age at presentation and in terms of clinical and immunological complications. In many cases, patients are referred to various specialists such as hematologists, rheumatologists, gastroenterologists, and others, before an immunological evaluation is performed, leading to delay in diagnosis, which negatively affects their prognosis. The significant heterogeneity in the clinical and immunological features affecting APDS patients requires awareness among clinicians since good results with p110δ inhibitors have been reported, certainly ameliorating these patients' quality of life and prognosis.


Everglades restoration and water quality challenges in south Florida.
This paper provides background information and a brief overview of water quality issues for the rest of the papers in this volume that are concerned with Everglades restoration. The Everglades of Florida have been diminished over 50% of their former extent. The Everglades are no longer a free-flowing wetland ecosystem, but are now subject to a complicated system of water management that is regulated primarily for flood control and consumptive use. Attempts to restore a more natural hydropattern to the remaining undeveloped Everglades are made more difficult by the natural extremes in rainfall, flat landscape, highly porous geology, and inaccessibility of the remaining natural areas. The Comprehensive Everglades Restoration Plan (CERP) seeks ecosystem restoration by adding water storage capacity, reducing groundwater seepage, improving regulatory delivery and timing of water to avoid environmental damage, and where feasible, improving the quality of water to be used for Everglades restoration. Water quality issues that currently exist for south Florida include eutrophication (especially phosphorus), mercury, and contaminants from agricultural production and the urban environment. Lands once in agricultural production that will be converted back to wetlands or will become reservoirs may contribute to the water quality concerns. Stormwater runoff from managed lands that will be used for restoration purposes will also present water quality challenges. The state continues to seek water quality improvement with a number of pollution reduction programs, and CERP attempts to improve water quality without sacrificing even more natural areas; however providing water quality sufficient for use in recovery of remaining Everglades wetlands and estuaries will remain a daunting challenge.


Functional activation of the human frontal cortex during the performance of verbal working memory tasks.
Regional cerebral blood flow was measured with positron emission tomography during the performance of verbal working memory tasks. The same type of verbal response (i.e., reciting numbers) was required in the control and the two experimental tasks. In the control task, the subjects were required to count aloud. In the two experimental tasks, the subjects were required to maintain within working memory the numbers they generated (self-ordered task) or the numbers generated by the experimenter (externally ordered task). Examination of the difference in activation between these conditions revealed strong bilateral activation within the mid-dorsolateral frontal cortex during both experimental tasks. There was, however, no evidence of additional activation within the mid-dorsolateral frontal cortex when monitoring self-generated responses as compared with the monitoring of externally generated responses. These results provide evidence regarding the role of the mid-dorsolateral frontal cortex in mnemonic processing that are in agreement with recent findings from work with non-human primates.


Step by step: integrating evidence-based fall-risk management into senior centers.
Our purpose in this project was to conceptualize and implement evidence-based fall-prevention programming into senior centers. We present challenges to this process and strategies to overcome them. We carried out a dissemination project in nine diverse senior centers in Connecticut. Participants included investigators from the Connecticut Collaboration for Fall Prevention (CCFP), senior center administrators, and trained staff interventionists implementing a program of fall prevention based on the Yale Frailty and Injury Cooperative Studies of Intervention Trials (known as the Yale FICSIT). Using CCFP materials that were based on the stages of change, senior center staff developed methods to integrate fall-prevention programming into their centers. We extracted implementation challenges, and the strategies that senior center staff developed to overcome them, from the minutes of monthly work-group meetings. Monthly counts of individual assessments were also a source of data. Challenges included staffing and the delineation of authority, structural issues, engaging senior center membership, cultural issues, and the modification of existing practices. Each senior center devised site-specific methods to overcome these challenges when CCFP investigators convened work-group meetings. We developed creative strategies to inform senior center membership about fall prevention, and in the first 18 months, 4% of members scheduled individual assessments. The challenges of integrating evidence-based fall-prevention programming into existing senior center services can be negotiated by collaboration among senior center administrators, health providers, the center membership, and researchers. This experience suggests that senior centers may be important venues to reach older adults with fall-prevention programming.


Optical Indicators based on Structural Colored Polymers.
Polymer indicators are autonomous responsive materials that provide an optical signal of a specific exposure in time. This review describes the different polymer systems utilized to obtain indicators based on structural color. Structural color originates from the interaction of light with a periodic nanostructured polymer which causes a specific wavelength to be reflected. This reflected light can be used for fabricating battery-free indicators that show visible structural color changes upon exposure to a stimulus or analyte. In this review, the typical structural color response types categorized by stimulus are discussed and compared. Furthermore, the steps toward possible applications of optical indicators based on structural colored polymers are outlined.


Influenza--insights from mathematical modelling.
When the first cases of a new infectious disease appear, questions arise about the further course of the epidemic and about the appropriate interventions to be taken to protect individuals and the public as a whole. Mathematical models can help answer these questions. In this article, the authors describe basic concepts in the mathematical modelling of infectious diseases, illustrate their use with a simple example, and present the results of influenza models. Description of the mathematical modelling of infectious diseases and selective review of the literature. The two fundamental concepts of mathematical modelling of infectious diseases-the basic reproduction number and the generation time-allow a better understanding of the course of an epidemic. Modelling studies based on past influenza epidemics suggest that the rise of the epidemic curve can be slowed at the beginning of the epidemic by isolating ill persons and giving prophylactic medications to their contacts. Later on in the course of the epidemic, restricting the number of contacts (e.g., by closing schools) may mitigate the epidemic but will only have a limited effect on the total number of persons who contract the disease. Mathematical modelling is a valuable tool for understanding the dynamics of an epidemic and for planning and evaluating interventions.


Phase II trial of sunitinib in patients with metastatic non-clear cell renal cell carcinoma.
Sunitinib is associated with a robust objective response rate in patients with metastatic clear cell renal cell carcinoma (RCC). The primary objective of this phase II clinical trial was to assess the overall response rate for sunitinib in patients with papillary metastatic RCC as well as other non-clear cell histologies. A Simon 2-stage design was used to determine the number of papillary metastatic RCC patients for enrollment, and allowed for descriptive response data for other non-clear cell histologies. Twenty-three patients were enrolled, including 8 with papillary renal cell carcinoma (RCC) and the remainder with other non-clear cell histologies (unclassified in 5 patients). All patients received 50 mg of oral sunitinib in cycles of 4 weeks followed by 2 weeks of rest (4/2). The trial was stopped early because of slow accrual; no responses were observed in the 8 patients with papillary RCC. In the 22 evaluable patients, best response to sunitinib included a partial response in 1 patient with unclassified RCC, stable disease in 15, and progression in 6. The median progression-free survival was 5.5 months (95% CI, 2.5-7.1) in all 23 patients, and 5.6 months for the 8 papillary patients (95% CI, 1.4-7.1). The robust objective responses sunitinib had produced in clear cell RCC could not be demonstrated in this study comprised of patients with non-clear cell histologies.


Association of Ki-67 antigen and p53 protein at invasive tumor front of oral squamous cell carcinoma.
Studies reveal that invasive tumor front may be the best field for quantification of proliferative and apoptotic markers. The current study assessed the expression of Ki-67 antigen and p53 protein at invasive tumor front of oral squamous cell carcinoma (OSCC) and correlated the immunostaining with the histologic grades of malignancy. A total of 80 slides sample was prepared for the study, one each from ten normal oral mucosa cases and two each from 30 OSCC cases. The OSCC patients were biopsied along invasive tumor front, and samples were immunohistochemically analyzed for the expression of both Ki-67 antigen and p53 protein. Of the total 30 OSCC cases, the expression of p53 was found positive in 20 cases (66.6%), while Ki-67 expression was found positive in 21 cases (70%). All the cases in the control group were negative. A higher p53 and Ki-67 expression were seen in OSCC group as compared to normal mucosa. On comparing the control group with various grades of OSCC a statistically significant result was obtained. Higher and statistically significant expression was noted for both p53 and Ki-67 antigen. The results emphasize the potential of Ki-67 and p53 as biomarkers of carcinogenesis in OSCC. Ki-67 expression was comparatively higher when compared with p53 except in poorly differentiated squamous cell carcinoma and signifies actively proliferating malignant cells at invasive tumor front.


Design and assessment of cost-effectiveness studies in AIDS populations.
Cost-effectiveness (CE) ratios are indicators of comparative efficiency of competing drugs. Unfortunately, they are subject to variations, depending on factors such as the study population chosen, the comparison treatment selected, and the economic analysis methods employed. CE ratios tend to be unfavorably skewed in the case of chronic illnesses, such as HIV disease, because management of AIDS patients is costly and complex. Routine AIDS therapy requires expensive drugs, treatment is directed at many disease stages and severities, and gain in patient survival is relatively short. Variations in disease stage, co-morbidities, and antiviral drug use produce variations in both the risk of opportunistic infections (OIs) and the routine costs of OI prophylaxis and thus affect the CE ratio. Routine therapy for AIDS varies among and even within communities. Overall, these factors translate to a widening gap between trial results (efficacy) and community outcomes (effectiveness). This article discusses these concerns and reviews methodologic issues that must be considered by decision-makers using CE analyses to describe a therapy's value.


Expression of luteinizing hormone receptors in the mouse penis.
The role of luteinizing hormone (LH) in the regulation of normal reproductive functions in males and females is quite well established. Besides the expression of LH receptors in the target cells in gonads, it has been found in several extragonadal organs. There is no information about the expression of LH receptors in the penis up to now. The aim of the present study is to investigate the expression of the LH receptor in the mouse penis to see if LH effects are possible in the penis. BALB/c mice were used as donors of normal penis and testis tissue. Immunocytochemistry, Western blotting, and quantitative reverse transcriptase polymerase chain reactions (RT-PCRs) were used for the detection of the LH receptor. Positive immunoreaction for LH receptors was present in the nuclei of urethral epithelium and endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis. Western blotting experiments demonstrated the presence of LH antigen at M(r) = 97.4 and 78 kd. Quantitative RT-PCRs confirmed the expression of LH receptor in the penis. Our results show that LH receptor is expressed in the body of the mouse penis; thus, it may directly regulate functions of penile tissue.


The role of myc in transformation by BCR-ABL.
The BCR-ABL gene plays a central role in the pathogenesis of chronic myelogenous leukemia. Despite a detailed understanding of the regions of BCR and ABL required for transformation by BCR-ABL, little is known about the signalling pathway by which BCR-ABL causes transformation. The nuclear oncogene c-myc plays a critical role in BCR-ABL transformation. Levels of c-myc RNA are high in cells transformed by BCR-ABL, and overexpression of dominant negative forms of myc blocks transformation by BCR-ABL. These findings suggest that myc may be a useful therapeutic target in BCR-ABL-related leukemias.


Elucidating the charge storage mechanism of carbonaceous and organic electrode materials for sodium ion batteries.
Sodium ion batteries (SIB) have received much research attention in the past decades as they are considered to be one alternative to the currently prevalent lithium ion batteries, and carbonaceous and organic compounds present two promising classes of SIB electrode materials advantaged by abundance of their constituent elements and reduced environmental footprints. To accelerate the development of these materials for SIB applications, future research directions must be guided by a thorough understanding of the charge storage mechanism. This review presents recent efforts in mechanism elucidation for these two classes of SIB electrode materials since, compared to their inorganic counterparts, they have unique challenges in material analysis. Topics covered will include characterization techniques and analytical frameworks for mechanism elucidation, emphasizing the advantages and limitations of individual experimental methodologies and providing a commentary on scientific rigor in result interpretation.


Effects of Fathers on Adolescent Daughters' Frequency of Substance Use and Risky Sexual Behavior.
This research: (1) implements a genetically informed design to examine the effects of fathers' presence-absence and quality of behavior during childhood/adolescence on daughters' frequency of substance use during adolescence; and (2) tests substance use frequency as mediating the relation between paternal behavior and daughters' sexual risk taking. Participants were 223 sister dyads from divorced/separated biological families. Sisters' developmental exposure to socially deviant paternal behavior predicted their frequency of tobacco, alcohol, and cannabis (TAC) use. Older sisters who co-resided with fathers who were more (vs. less) socially deviant reported more frequent TAC use during adolescence. More frequent TAC use predicted more risky sexual behavior for these daughters. No effects were found for younger sisters, who spent less time living with their fathers.


Lipid extraction from wet Nannochloropsis biomass via enzyme-assisted three phase partitioning.
A green and efficient enzyme assisted three phase partitioning (EA-TPP) process was firstly developed to extract microalgal lipids using wet Nannochloropsis sp. biomass. In the pretreatment of microalgal biomass by four hydrolytic enzymes, TPP obtained a higher TFAs lipid extraction efficiency by cellulase compared with the resting enzymes. After optimization by EA-TPP of the wet disrupted Nannochloropsis biomass (3 g), the maximum TFAs extraction yield (90.40%) was attained at 20% ammonium sulphate, 6-7 pH, 1:2 slurry/tert-butanol ratio and 70 °C for 2 h incubation time and two extraction cycles. Moreover, results also revealed that the lipidic species compositions of Nannochloropsis sp. biomass were greatly related with the EA-TPP parameters. In the laboratory scale for wet disrupted microalgae biomass, EA-TPP process achieved 88.70% TFAs extraction yield under the optimized conditions. In all, EA-TPP process could be a promising approach to extract microalgae lipids for food application using wet microalgae biomass.


Medical school dean as a turnaround agent.
Taking on the role as a new medical school Dean in a new city after Hurricane Katrina posed many challenges. To facilitate turnaround, 3 principles were applied: hit the ground running, promote community involvement, and gain a common vision for the future. This article describes Tulane University's process for implementing change and expands on its vision for the future.


Evaluation of status of cadmium, lead, and nickel levels in biological samples of normal and night blindness children of age groups 3-7 and 8-12 years.
The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood trace metals toxicity, which is the most common problem found in underdeveloped countries. This study was designed to compare the levels of cadmium (Cd), lead (Pb), and nickel (Ni) in scalp hair, blood, and urine of night blindness children age ranged 3-7 and 8-12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of Cd, Pb, and Ni in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cd, Pb, and Ni by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cd, Pb, and Ni in the biological samples (blood, scalp hair, and urine) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating toxicity of trace metals in biological samples of night blindness children.


Membrane damage caused by free radicals--radiation perspective.
Irradiation experiments were performed with Ehrlich ascites tumour cells grown in the peritoneal cavity of mice. A 20 MeV proton beam was used as the source of ionizing radiation. The generation of free radicals was investigated with EPR spectrometry. Lipid peroxidation products were determined by the thiobarbiturate reaction, UV-absorption, and fluorometric measurements. Membrane injuries were visualized by electron microscopy. Free radicals (like H and OH) were formed in the cells during the irradiation. Radical reactions were transferred to membrane lipids producing secondary radicals, diene conjugation, malondialdehyde formation and fluorescent end products. By using electron microscopy severe damage could be detected in cell membranes.


[Resection of the trachea for cicatrical stenosis].
Tracheal stenosis represents a serious complication of tracheostomy or of endotracheal intubation. The objective of this article was to evaluate the results of resective therapy of patients with tracheal stenosis. In 41 patients treated by tracheal resection for tracheal stenosis the diagnosis was established by bronchoscopy, tracheal tomography or CT. The following parameters were evaluated: the reasons for artificial pulmonary ventilation, basic parameters of stenosis (site of stenosis, length, diameter), the relationship between the duration of cannulation and asymptomatic interval, and postoperative complications. The most frequent reason for cannulation was trauma (n = 23), most patients were cannulated for 4-5 weeks (n = 16), the symptoms of stenosis appeared mostly within 4-5 weeks (n = 11) after decannulation. The asymptomatic interval was longer in patients with longer periods of cannulation (p < 0.01) than in patients with a shorter cannulation period. The most frequent site of stenoses was the medium third of the trachea (n = 22). The longest resected section measured 60 mm. In 3 patients (7.3 %) a tracheoesophageal fistula was found together with the stenosis. In 3 patients (7.3 %) restenosis appeared. Tracheocutaneous fistula with osteomyelitis of the sternum developed in one patient. Granulation tissue on the anastomosis site (n = 4, 9.7 %) was treated by laser or disappeared spontaneously. None of the patients died within 30 days after operation. Resection is the optimum therapeutic method for tracheal stenosis with low postoperative mortality and a small number of postoperative complications. Successful tracheal resection is a definitive solution in comparison with stent placement.


Sarcopenia assessment by new EWGSOP2 criteria for predicting chemotherapy dose-limiting toxicity in patients with gastrointestinal tract tumors.
In 2019, The EWGSOP2 group made updates on the definition and diagnosis of sarcopenia. The aim of this study is to determine the possible risk factors for chemotherapy dose-limiting toxicity (DLT). Newly diagnosed gastrointestinal (GI) cancer patients were included in this prospective observational study. Chemotherapy DLTs were recorded in patients receiving platinum-based therapy. The patients were divided into two groups according to the current sarcopenia criteria. 75 patients were included in the final analysis. Chemotherapy DLT occurred in 52% (n = 39) of all patients who received platinum-based chemotherapy. DLT rates were 78.9% and 42.9% in sarcopenic and non-sarcopenic patients, respectively (p = 0.007). According to the results of the multivariate analysis, the only sarcopenia was found as a statistically significant risk factor for DLT. Assessment of sarcopenia evaluated with the current EWGSOP2 diagnostic criteria is useful in predicting chemotherapy DLT development in patients with a diagnosis of GI cancer. In the future, current EWGSOP2 recommendations should be considered while designing a study investigating the correlation between sarcopenia and chemotoxicity.


Neural circuits for pain: Recent advances and current views.
The mammalian nervous system encodes many different forms of pain, from those that arise as a result of short-term low-grade interactions with noxious thermal, chemical, or mechanical sources to more serious forms of pain induced by trauma and disease. In this Review, we highlight recent advances in our understanding of the neural circuits that encode these types of pain. Promising therapeutic strategies based on recent advances are also highlighted.


Nonmedical prescription opioid use and mental health and pain comorbidities: a narrative review.
In North America, the prevalence of nonmedical prescription opioid use (NMPOU), and morbidity and mortality related to prescription opioid analgesics (POAs) has risen sharply. Epidemiologic studies have suggested a high prevalence of mental health and pain comorbidities in NMPOU samples. Given the potential importance for interventions, a narrative review was conducted on studies reporting data on the co-occurrence of NMPOU with mental health problems and pain symptoms in general, treatment, or special populations. A search of MEDLINE, PubMed, PsycINFO, and Web of Science using defined search terms yielded 74 studies on NMPOU and mental health and (or) pain. Thirty-nine studies published between 1997 and 2009 were included in the review-based on the data they provided on NMPOU and mental health and pain comorbidities. Our review found strong associations between NMPOU and the comorbidities of interest. Associations between NMPOU and mental health were strongest for depression (OR range 1.2 to 4.3) followed by anxiety disorders (OR range 1.2 to 3.0) in general and treatment populations. The prevalence of pain ranged from 14.5% to 61.5% in general, treatment, and street drug user samples reporting NMPOU. The extensive associations observed between NMPOU and mental health and pain comorbidities suggest that effective preventive or treatment interventions for NMPOU must consider and attend to these comorbidities. As POAs are widely available and used in North America, POAs may increasingly be used in nonmedical ways for pain or mental health problems not effectively diagnosed or treated.


Human Detection Using Random Color Similarity Feature and Random Ferns Classifier.
We explore a novel approach for human detection based on random color similarity feature (RCS) and random ferns classifier which is also known as semi-naive Bayesian classifier. In contrast to other existing features employed by human detection, color-based features are rarely used in vision-based human detection because of large intra-class variations. In this paper, we propose a novel color-based feature, RCS feature, which is yielded by simple color similarity computation between image cells randomly picked in still images, and can effectively characterize human appearances. In addition, a histogram of oriented gradient based local binary feature (HOG-LBF) is also introduced to enrich the human descriptor set. Furthermore, random ferns classifier is used in the proposed approach because of its faster speed in training and testing than traditional classifiers such as Support Vector Machine (SVM) classifier, without a loss in performance. Finally, the proposed method is conducted in public datasets and achieves competitive detection results.


Ovarian-cell-like cells from skin stem cells restored estradiol production and estrus cycling in ovariectomized mice.
Reduction of estradiol production and high serum concentrations of follicular stimulating hormone (FSH) are endocrine disorders associated with premature ovarian failure. Here, we report that transplantation of ovarian-like cells differentiated from stem cells restored endogenous serum estradiol levels. Stem cells were isolated from postnatal mouse skin and differentiated into ovarian-cell-like cells that are consistent with female germ, and ovarian follicle somatic cells. The ovarian-cell-like cells were transplanted into ovariectomized mice (Cell Trans), whereas control mice were subjected to bilateral ovariectomies without cell transplantation (OVX). Using vaginal cytology analysis, it was revealed that in 13 out of 19 Cell Trans mice, estrus cycles were restored around 8 weeks after cell transplantation and were maintained until 16 weeks post-transplantation, whereas in the OVX group, all mice were arrested at metestrus/diestrus of the estrus cycle. The uterine weight in the Cell Trans group was similar to sham operation mice (Sham OP), while severe uterine atrophy and a decreased uterine weight were observed in the OVX group. Histologically, ectopic follicle-like structures and blood vessels were found within and around the transplants. At 12-14 weeks after cell transplantation, mean serum estradiol level in Cell Trans mice (178.0±35 pg/mL) was comparable to that of the Sham OP group (188.9±29 pg/mL), whereas it was lower in the OVX group (59.0±4 pg/mL). Serum FSH concentration increased in the OVX group (1.62±0.32 ng/mL) compared with the Sham OP group (0.39±0.34 ng/mL). Cell Trans mice had a similar FSH level (0.94±0.23 ng/mL; P<0.05) to Sham OP mice. Our results suggest that ovarian somatic cells differentiated from stem cells are functional in vivo. In addition to providing insights into the function of ovarian somatic cells derived from stem cells, our study may offer potential therapeutic means for patients with hypo-estradiol levels like those encountered in premature ovarian failure.


Influence of ion-associated water on the hydrolysis of Si-O bonded interactions.
Previous studies show the demineralization of biogenic, amorphous, and crystalline forms of silica is enhanced in the presence of alkali and alkaline earth cations. The origins of this effect are difficult to explain in light of work suggesting predominantly weak outer-sphere type interactions between these ions and silica. Here we investigate the ability of M(II) aqua ions to promote the hydrolysis of Si-O bonded interactions relative to ion-free water using electronic structure methods. Reaction pathways for Si-O hydrolysis are calculated with the B3LYP and PBE1PBE density functionals at the 6-31G(d) and 6-311+G(d,p) levels in the presence of water, and both inner- and outer-sphere adsorption complexes of Mg(2+)(6H(2)O) and Ca(2+)(6H(2)O). All reaction trajectories involving hydrated ions are characterized by one or more surmountable barriers associated with the rearrangement of ion-associated water molecules, and a single formidable barrier corresponding to hydrolysis of the Si-O bonded interaction. The hydrolysis step for outer-sphere adsorption is slightly less favorable than the water-induced reaction. In contrast, the barrier opposing Si-O hydrolysis in the presence of inner-sphere species is generally reduced relative to the water-induced pathway, indicating that the formation of inner-sphere complexes may be prerequisite to the detachment of Si species from highly coordinated surface sites. The results suggest a two-part physical model for ion-promoted Si-O hydrolysis that is consistent with experimental rate measurements. First, a bond path is formed between the cation and a bridging oxygen site on the silica surface that weakens the surrounding Si-O interactions, making them more susceptible to attack by water. Second, Si-O hydrolysis occurs adjacent to these inner-sphere species in proportion to the frequency of ion-associated solvent reorganization events. Both processes are dependent upon the particular ion hydration environment, which suggests measured cation-specific demineralization rates arise from differential barriers opposing reorganization of ion-associated solvent molecules at the silica-water interface.


The relationship between sexual abuse and purging: findings from community-wide surveys of female adolescents.
The first objective of this study was to examine the relationship between sexual abuse and a bulimic behavior, namely purging, with a large sample of female adolescents. If sexual abuse was found to be significantly related to bulimia, then the second objective was to determine if the relationship between abuse and purging remained significant when other factors were controlled. Two different analyses were conducted to address the questions outlined above--a contingency table chi-square test and a logistic regression analysis. A sample of 7,903 female adolescents was drawn from a large Midwestern state. The results of the bivariate analysis provide evidence that a relationship exists between sexual abuse and purging. However, the relationships between sexual abuse and purging did not remain significant when several other factors, including physical abuse, were included in the analysis. Several individual (a history of physical abuse and religiosity), familial (i.e., family support and parent-adolescent communication), and extra-familial (i.e., other adult support) factors were significantly related to purging. The data did not find a significant relationship between sexual abuse and purging when individual, familial, and extra-familial variables were included in the logistic regression. Unlike most earlier studies that focused on clinical samples, this study drew from a larger, more representative sample of female adolescents. The identification of significant predictors of purging at the individual, familial, and extra-familial levels suggests the importance of examining multiple levels of the teen's ecology for factors that may influence this behavior.


Effect of relining on fiber post retention to root canal.
One of the clinically relevant problems dentists face when restoring endodontically treated teeth is the mismatch between fiber post and post space diameters, which results in an excessively thick resin cement layer. Fiber post relining appears as a solution for this problem. The aim of this study was to evaluate the effect of fiber post relining with composite resin on push-out bond strength. Twenty bovine incisors were selected to assess post retention. The crowns were removed below the cementoenamel junction and the root canals were treated endodontically and flared with diamond burs. The roots were allocated into two groups (n=10): G1: fiber posts without relining and G2: fiber posts relined with composite resin. The posts were cemented with a dual-cured resin cement and the specimens were sectioned transversally. Three 1.5-mm thick slabs were obtained per root and identified as cervical, medium and apical thirds. The push-out test was performed at a crosshead speed of 0.5 mm/min until post dislodgement occurred. The failure mode of fractured specimens was analyzed under scanning electron microscopy. Data were analyzed by split-plot ANOVA and post-hoc Tukey's test at a pre-set alpha of 0.05. Relined fiber posts presented higher retention values than non-relined post in all thirds. No statistically significant differences (p>0.05) were found among thirds for relined posts. All failures occurred at the interface between resin cement and root dentin. Relining with composite resin seems to be an effective method to improve the retention of fiber posts to flared root canals.


Antileukemic activity of recombinant humanized M195-gelonin immunotoxin in nude mice.
A leukemia-selective immunotoxin was constructed by linking recombinant gelonin (rGel), a single chain ribosome inhibitory protein, to recombinant humanized M195 antibody (HuM195), which recognizes the cell-surface protein designated CD33. CD33 is an antigen found on myeloid leukemia blasts as well as myeloid progenitor cells but it is not expressed in detectable amounts on the ultimate hematopoietic progenitor stem cell. Our previous studies indicated that a non-recombinant humanized immunotoxin displayed specific, potent toxicity towards CD33-positive cells but not to CD33-negative cells in vitro. In the current study, a recombinant humanized immunotoxin, HuM195-rGel, was evaluated in vivo in a nude mouse model of human myeloid leukemias. HuM195-rGel was found to target leukemia cells rapidly in vivo and was subsequently internalized into the cells. For trials in vivo, nude mice were injected (ip) with 10(7) log-phase HL60 human leukemia cells 10 days prior to the start of i.p. HuM195-rGel treatments. HuM195-rGel demonstrated significant tumor suppressive activity in this model. While all mice treated with either saline, rGel alone, or HuM195 plus unconjugated rGel (at 10 or 14 days after transplantation) had rapid tumor growth or early deaths, 50% of mice treated with HuM195-rGel failed to develop leukemic tumors for 5 months and the 50% had significantly retarded tumor growth after treatment with HuM195-rGel. Mice treated at later times (28 days after transplantation of leukemia cells) also showed delayed leukemia cell growth, but no cures. These data show that HuM195-rGel can target leukemia cells in vivo and can result in pronounced anti-leukemic effects.


Circular RNAs: Biogenesis, properties, roles, and their relationships with liver diseases.
Circular RNAs (circRNAs) are a class of new-found RNA molecules that have a special covalent loop structure without a 5' cap and 3' tail. Researchers have found that circRNAs may be generated by intron-pairing-driven or lariat-driven circularization. They are cleared up by way of extracellular vesicles. They have some advantages such as stability, conservation, and tissue specificity. By serving as sponges of microRNAs, interacting with long non-coding RNAs, mRNA, or proteins, circRNAs regulate gene expression at transcriptional and post-transcriptional levels and contribute to carcinogenesis. In recent years, circRNAs have been found to be correlated with many cancers including hepatocellular carcinoma, one of the most common cancers with high mortality. This article will first introduce the biogenesis, properties, and functions of circRNAs. Then we focus on the molecular mechanisms underlying some circRNAs, including hsa_circ_0001649, hsa_circ_0005075, and cerebellar degeneration-related protein 1 antisense, on hepatocellular carcinoma metastasis.


Anodized Nickel Foam for Oxygen Evolution Reaction in Fe-Free and Unpurified Alkaline Electrolytes at High Current Densities.
To achieve practically high electrocatalytic performance for the oxygen evolution reaction (OER), the active surface area should be maximized without severely compromising electron and mass transport throughout the catalyst electrode. Though the importance of electron and mass transport has been studied using low surface area catalysts under low current densities (∼tens of mA/cm2), the transport properties of large surface area catalysts under high operating current densities (∼500 mA/cm2) for practical OER catalysis have rarely been explored. Herein, three-dimensional (3D) hierarchically porous anodized nickel foams (ANFs) with large and variable surface areas were synthesized via electrochemical anodization of 3D nickel foam and applied as OER electrocatalysts in Fe-free and unpurified KOH electrolytes. Using Fe-free and in situ Fe-doped ANF that were prepared in Fe-free and unpurified electrolytes, respectively, we investigated the interdependent effects of active surface area and transport properties on OER activity under practically high current densities. While activity increased linearly with active surface area for Fe-free ANF, the activity of Fe-doped ANF showed a nonlinear increase with active surface area due to lower electrocatalytic activity enhancement. Detailed investigations on the possible factors (Fe incorporation, mass transport, and electron transport) identified that electron transport limitations played the major role in restricting the activity enhancement with increasing active surface area for Fe-doped ANF, although Fe-doped ANF has electron transport properties better than those of Fe-free ANF. This study exemplifies the growing significance of electron transport properties in large surface area catalysts, especially those with superb intrinsic catalytic activity and high operating current density.


The effect of acute vibration exercise on short-distance sprinting and reactive agility.
Vibration exercise (VbX) has been a popular modality to enhancing physical performance, where various training methods and techniques have been employed to improve immediate and long-term sprint performance. However, the use of acute side-alternating VbX on sprint and agility performance remains unclear. Eight female athletes preformed side-alternating vibration exercise (VbX) and control (no VbX) in a cross over randomised design that was conducted one week apart. After performing a warm-up, the athletes undertook maximal 5m sprints and maximal reactive agility sprints (RAT), this was followed by side-alternating VbX (26 Hz, 6mm) or control (no VbX). Immediately following the intervention, post-sprint tests and RAT were performed. There was a significant treatment effect but there was no time effect (pre vs. post) or interaction effect for sprint and RAT; however, side-alternating VbX did not compromise sprint and agility performance. Key PointsAcute VbX could be beneficial for the acceleration phase (1.5m) of a short-distance sprint.Acute VbX does not have positive influence on short-distance (3m & 5m) sprint performance.Acute VbX does not enhance reactive agility performance.


Six-month effects of a thermodynamic treatment for MGD and implications of meibomian gland atrophy.
The aim of this study was to evaluate the 6-month effect of a single automated thermodynamic treatment (LipiFlow) and implications of meibomian gland atrophy on treatment efficacy 6 months after application. We analyzed the data of 26 subjects with meibomian gland dysfunction before and 6 months after treatment. Investigated parameters included subjective symptoms, lipid layer thickness, meibomian gland assessment, tear osmolarity, corneal and conjunctival staining, lid margin parallel conjunctival folds, Schirmer test values, bulbar redness, tear meniscus height, meibomian gland atrophy, and noninvasive tear break-up time. Subjective symptoms (mean Ocular Surface Disease Index, 42 ± 19 to 33 ± 21; P = 0.004, mean Standard Patient Evaluation of Eye Dryness 16 ± 7 to 12 ± 7; P = 0.0001), lipid layer thickness (44.0 ± 15.6 to 51.3 ± 20.4; P = 0.014), number of expressible glands (2.9 ± 1.6 to 6.4 ± 4.6; P < 0.0001), lid margin parallel conjunctival folds (2.3 ± 1.0 to 2.0 ± 0.9; P = 0.04), and bulbar redness (1.4 ± 0.5 to 1.2 ± 0.5; P = 0.0001) were all improved 6 months after treatment. Symptomatic improvement was higher in patients with less severe meibomian gland atrophy compared with patients with more dropout at treatment. There was no change of meibomian gland atrophy 6 months after treatment. In summary, the results showed that a single thermodynamic treatment is effective in the treatment of meibomian gland dysfunction and that the effects last for at least 6 months. We suggest performing meibography in every patient before treatment for better prediction of therapeutic effects.


Anti-interleukin-6 therapy in rheumatoid arthritis.
Recent advances in research have led to significant progress in unraveling the pathophysiology of rheumatoid arthritis (RA), including the cytokine-mediated signaling process. While therapies targeting one particular cytokine, tumor necrosis factor-alpha (TNF-α), have revolutionized the treatment of RA, other cytokines, including interleukin 6 (IL-6,) have been implicated in the disease process. In this review, we describe the research that ultimately led to large, randomized, controlled trials demonstrating the effectiveness of tocilizumab, a monoclonal antibody directed against the IL-6 receptor, as a potent new therapeutic agent in RA treatment. These data have shown this agent to be effective both in patients failing non-biologic DMARDs and those failing anti-TNF therapy, although the drug is currently approved for use only in the latter situation. Adverse events seen with tocilizumab therapy are also reviewed.


Tumor-derived DNA from pleural effusion supernatant as a promising alternative to tumor tissue in genomic profiling of advanced lung cancer.
Pleural effusion (PE) is commonly observed in advanced lung cancer and was suggested to contain both cell-free tumor DNA and tumor cells. Molecular profiling of PE represents a minimally invasive approach of detecting tumor driver mutations for clinical decision making, especially when tumor tissues are not available. The objective of this study is to investigate the efficacy and precision of detecting gene alterations in PE samples to address the feasibility in clinical use. Methods: Sixty-three metastatic lung cancer patients with (n=30, cohort 1) or without (n=33, cohort 2) matched tumor tissues were enrolled in this study. PE and plasma samples of each patient were collected simultaneously. Supernatant and cell precipitate of PE were processed separately to extract cfDNA (PE-cfDNA) and sediment DNA (sDNA). All samples were subjected to targeted next-generation sequencing (NGS) of 416 cancer-related genes. Results: PE supernatants contain more abundant tumor DNA than PE sediments and plasma samples, suggested by higher mutant allele frequencies (MAF) and elevated mutation detection rate in PE-cfDNA (98.4% vs. 90.5% in PE sDNA vs. 87% in plasma cfDNA). In Cohort 1 with matched tumor tissue, tumor mutational burden (TMB) of PE-cfDNA was similar as tumor tissues (6.4 vs. 5.6), but significantly higher than PE sDNA (median TMB: 3.3) and plasma cfDNA (median TMB: 3.4). Ninety-three percent (27 out of 29) of tissue-determined driver mutations were detected in PE-cfDNA, including alterations in ALK, BRAF, EGFR, ERBB2, KRAS, NF1, PIK3CA, and RET, while only 62% were captured in plasma cfDNA. PE-cfDNA also has the highest detection rate of EGFR driver mutations in the full cohort (71% vs. 68% in PE sDNA vs. 59% in plasma cfDNA). Mutation detection from cytological negative and hemorrhagic PE is challenging. Comparatively, PE-cfDNA demonstrated absolute superiority than PE sDNA in such a scenario, suggesting that it is an independent source of tumor DNA and therefore less influenced by the abundance of tumor cells. Conclusion: Genomic profiling of PE-cfDNA offers an alternative, and potentially more meticulous approach in assessing tumor genomics in advanced lung cancer when tumor tissue is not available. Our data further demonstrate that in hemorrhagic or cytologically negative PE samples, PE-cfDNA has higher mutation detection sensitivity than sDNA and plasma cfDNA, and therefore is a more reliable source for genetic testing.


The impact of stroke: are people with aphasia different to those without?
Stroke rehabilitation programmes aim to improve functional outcomes and quality of life. This study explored long-term outcomes in a cohort of people admitted to two acute stroke units with stroke. Comparisons were drawn between people with aphasia (PWA) and people without aphasia. People admitted to hospital with a first stroke were assessed at 2-weeks, 3-months and 6-months post-stroke. Measures included: the Barthel Index for Activities of Daily Living (ADL), the Frenchay Aphasia Screening Test, the General Health Questionnaire-12 for emotional well-being and the Stroke and Aphasia Quality of Life Scale-39g. Extended ADL and social support were also measured at 3 and 6 months, with the Frenchay Activities Index and the Social Support Survey, respectively. Of 126 eligible participants, 96(76%) took part and 87(69%) were able to self-report. Self-report data are reported here. Although outcomes improved significantly across time, at 6 months people continued to experience substantial functional limitations (16% aphasic; 32% dependent on basic ADL); participation limitations (79% ≤30 on the FAI); high psychological distress (45%) and compromised quality of life (54% ≤4 on the SAQOL-39g). Levels of social support remained relatively stable. Though at 3-months post-stroke PWA were significantly more likely to experience high psychological distress (93% versus 50% for those without), across time, there were no significant differences between PWA and those without on psychological distress and also ADL and social support. There were, however, significant differences on extended ADL (F(1,68) = 7.80, p < 0.01) and quality of life (F(1,69) = 6.30, p < 0.05). PWA participated in fewer activities and reported worse quality of life after stroke than people without aphasia, even when their physical abilities, well-being and social support were comparable. Implications for clinical practice and future research are discussed.


Quality and quantity of price elasticity of cigarette in Iran.
Effectiveness of tax policies to control cigarette consumption largely depends on the sensitivity of cigarette demand due to price change. Price elasticity is the measurement of this responsiveness. The main objective of this study is to measure quantity, and quality price elasticity of demand (PED) and cross-price elasticity of demand (XED) for Iranian and non-Iranian cigarette brands in Iran. This study used data from the 2017 Iranian household income and expenditures survey conducted in all 31 provinces of Iran. A total of 39,864 households were included in the survey. PED of quantity and quality and XED were estimated using restricted, unrestricted and quintile regression models. Our results s show that the Iranian and non-Iranians brands cigarettes were price inelastic and elastic, respectively. XED between Iranian and non-Iranian brands was positive suggesting households' preference for Iranian brands of cigarettes over non-Iranian brands. Quintile regression results suggest that PED varied between -1.20 and -0.91 across the distribution of quantity demanded. Imposing tax could be a useful policy tool to control smoking initiation and intensity in Iran. However, the effectiveness of such policy would depend on the better governance of taxation imposed on different brands of cigarettes.


[Difficulties in the diagnosis of hereditary familial amyloidosis].
A 24-year-old woman had fever with skin rash, marked hepatolienal syndrome from the age of 1.5 years followed in later life by involvement of central nervous system and kidneys. Morphologically, there was accumulation of amyloid FAP in hepatic and rectal tissues. Family history of amyloidosis and the above evidence confirmed hereditary nature of the disease.


Caspase-dependent cleavage of ErbB-2 by geldanamycin and staurosporin.
The geldanamycin-induced degradation of ErbB-2 produces a 23-kDa carboxyl-terminal fragment, which has been isolated and subjected to amino-terminal microsequencing. The obtained sequence indicates that the amino terminus of this fragment corresponds to Gly-1126 of ErbB-2. Analysis of the residues immediately before Gly-1126 suggests that cleavage may involve caspase activity. Site-directed mutagenesis of Asp-1125 in ErbB-2 prevents geldanamycin-provoked formation of the 23-kDa fragment, consistent with the requirement of this residue for caspase-dependent cleavage in known substrates. Also, the addition of the pan-caspase inhibitor Z-VAD-FMK blocks formation of the 23-kDa ErbB-2 fragment in cells exposed to geldanamycin. Interestingly, staurosporin and curcumin are also shown to provoke the degradation of ErbB-2 with formation of the 23-kDa carboxyl-terminal fragment. The generation of this fragment by staurosporin or curcumin is likewise blocked by caspase inhibition. Caspase inhibition does not prevent accelerated degradation of the 185-kDa native ErbB-2 in geldanamycin-treated cells but does significantly prevent staurosporin-stimulated metabolic loss of ErbB-2.


[Blood levels of cyclosporine, acute rejections and the prognosis of the allografts in pediatric renal allograft recipients].
Results of a total of 46 pediatric (mean age; 9.0 years), living-related, cyclosporine-treated renal allograft recipients were analyzed retrospectively to study 1), the effects of an acute rejection on the long-term allograft function and 2), the relationship between the cyclosporine blood levels and the frequency of acute rejections. In addition, sequential allograft biopsies (100 days, one, two and three years post-transplant) were performed in all cases to see if clinical symptoms correlated with histological changes. After a mean follow up of 3.3 (range 1-6) years, 15 of 22 (68%) recipients who had no signs of acute rejection, 6 of 12 (50%) who had acute rejections but responded completely to therapy, and none of the remaining 12 cases who failed to recover completely from acute rejections showed good allograft functions and normal histology on biopsy. Thirty-four of 46 cases had no clinical signs of rejection at 100-day allograft biopsy. Yet, histological changes compatible with acute rejection were noted in 11 of 34. Treatments of the rejection were promptly started on these patients and the prognosis was excellent in six cases. The mean blood trough levels of cyclosporine were significantly lower in patients who developed an acute rejection during the first week following transplantation as compared to those without rejection episodes during the same period, 165.5 ng/ml and 204.1 ng/ml, respectively. Furthermore, the mean blood cyclosporine trough levels in patients who experienced rejections during two, three and five weeks after transplantation were definitely lower than those who did not experience such episodes; 124.5 ng/ml, 101 ng/ml and 149.3 ng/ml versus 241.7 ng/ml, 217.7 ng/ml and 201.1 ng/ml respectively, although the number of the cases was too small to reach statistical significance. The results indicate that the long-term allograft function would depend on whether there were episodes of acute rejections, and/or how the allograft responded to the treatments. Since the introduction of cyclosporine has made it difficult to detect acute rejections by clinical findings alone such as blood chemistry or urinalysis, the role of routine allograft biopsies is very important in renal transplantation. It seems likely that low blood levels and/or acute decline of cyclosporine during early postransplant period could increase the possibility of episodes of acute rejection. Since it is well documented that cyclosporine induces less renal parenchymal damages in children, the blood through levels of the drug should be kept at between 200 and 300 ng/ml within 5 weeks of transplantation in order to reduce the risk of acute rejections and to improve the chance of long-term allograft survival.


Evidence of a direct TRH effect on the rat exocrine pancreas.
In the present study, the effect of TRH on amylase secretion was determined both in vivo, by cannulating the pancreatic duct of rats, as well as in vitro, by using isolated lobules and dissociated acini. The results show that TRH inhibited both basal and stimulated in vivo amylase secretion. Nevertheless, the in vitro experiments failed to show a TRH-related inhibitory effect when TRH was used alone, although the hormone did blunt the secretion elicited by CCK8 and bethanechol from isolated lobules and dissociated acini. Results suggest that TRH can inhibit stimulated amylase secretion in rats through a direct effect on acinar cells.


MoS2 Quantum Dots@TiO2 Nanotube Arrays: An Extended-Spectrum-Driven Photocatalyst for Solar Hydrogen Evolution.
TiO2 nanotube arrays (TiO2 NTAs) decorated with molybdenum disulfide quantum dots (MoS2 QDs) were synthesized by a facile electrodeposition method and used as a composite photocatalyst. MoS2 QDs/TiO2 NTAs showed enhanced photocatalytic activity compared with pristine TiO2 NTAs for solar light-promoted H2 evolution without adding any sacrificial agents or cocatalysts. The photocatalytic activity was influenced by the amount of MoS2 QDs coated on TiO2 NTAs. The optimal composition showed excellent photocatalytic activity, achieving H2 evolution rates of 31.36, 5.29, and 1.67 μmol cm-2 h-1 corresponding to ultraviolet (UV, λ<420 nm), visible (Vis, λ≥420 nm), and near-infrared (NIR, λ>760) illumination, respectively. The improved photocatalytic activity was attributed to the decreased bandgap and the surface plasmonic properties of MoS2 QDs/TiO2 NTAs, which promoted electron-hole pair separation and the absorption capacity for Vis and NIR light. This study presents a facile approach for fabricating MoS2 QDs/TiO2 NTA heterostructures for efficient photocatalytic H2 evolution, which will facilitate the development of designing new photocatalysts for environment and energy applications.


Triplication of Ureter: A Rare Case.
Anatomical fusion abnormalities of the urinary system and ureters are not uncommon. However, triplication of the ureter is very rare. A boy with this abnormality is being presented in view of its rarity. The importance of a thorough preoperative evaluation is being projected that may help us to choose the best management avenue.


Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia.
Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalation anaesthetics and depolarizing neuromuscular blocking agents. To date, eight mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in malignant hyperthermia susceptible (MHS) and central core disease (CCD) cases. We have screened the RYR1 gene in affected individuals for novel MHS mutations by single stranded conformational polymorphism (SSCP) analysis and have identified a G to T transition mutation which results in the replacement of a conserved arginine (Arg) at position 614 with a leucine (Leu). The Arg614Leu mutation was present in three unrelated MHS individuals of 151 investigated. The mutation was not detected in 148 normal chromosomes and segregated precisely with MHS in family members from one of the probands where DNA was available for analysis. This mutation occurs at the same position as the previously identified Arg to Cys mutation reported in all cases of porcine MH and in approximately 5% of human MH. A comparison of the phenotypes of the Arg614Leu and Arg614Cys probands is presented.


Determination of Trace Phosphoprotein in Food Based on Fluorescent Probe-Triggered Target-Induced Quench by Electrochemiluminescence.
Evaluation of the nutrition and determination of phosphoproteins is of great importance in different foods as aberrant phosphorylation changes many biological processes and can relate to health conditions. In this study, an ultrafast (5 min) and sensitive electrochemiluminescence (ECL) sensor was innovatively fabricated for the determination of phosphoproteins in foods on the basis of fluorescent probe NH2-TiO2/upconversion nanomaterials (UCNPs). Impressively, the ECL intensity of NH2-TiO2/UCNPs-rGO/GCE was remarkably enhanced by 29 times. Furthermore, the photoactive NH2-TiO2 layer provided not only specific selectivity but also a large surface area as well as an unprecedented photocatalytic activity for the NH2-TiO2/UCNPs-rGO/GCE ECL sensor (TIECLS), which could serve as an identification element for trace phosphoproteins. Under optimal conditions, the TIECLS achieved a relatively low detection limit of 9.2 × 10-5 mg/mL (S/N = 3). Practical application of this TIECLS was carried out in different food samples with satisfying results, which were validated by laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS).


Periodontal plastic surgery associated with treatment for the removal of gingival overgrowth.
Excisional biopsies of gingival overgrowths, performed with safety margins, frequently result in mucogingival defects. These defects may produce esthetic problems and increase the chances of dentin hyperesthesia and its possibility of hindering oral hygiene. Two clinical cases are reported in which gingival overgrowths were removed by excisional biopsy, resulting in unsightly defects. The first clinical case presents an invasive approach for the treatment of a recurrent pyogenic granuloma in the anterior maxilla, and the second depicts a complete removal of a peripheral odontogenic fibroma in the posterior maxilla. In both situations, the soft-tissue defects were repaired by periodontal plastic surgery, including a laterally positioned flap and a coronally positioned flap, respectively. Periodontal plastic surgery successfully restored the defects that resulted from biopsies, and no recurrence has been noticed in the 5-year postoperative follow-up period. The combination of biopsy and periodontal plastic surgery in a one-step procedure seems to be suitable to remove gingival overgrowths in most areas of the mouth, regardless of esthetic significance. Such procedures seem to restore gingival health, encourage healing, and create both esthetics and function in the excised area.


[Prevention and management of anastomotic bleeding after laparoscopic anterior resection of rectal cancer].
In recent years, the laparoscopic anterior rectal cancer resection is increasingly applied in clinical practice, however, laparoscopic operations and stapling techniques can bring a series of related complications. The anastomotic bleeding is one of the early complications in laparoscopic anterior rectal cancer resections. If the continuous anastomotic bleeding is not diagnosed or managed in time, it could lead to serious consequences, such as secondary surgery and shock. Therefore, the diagnosis and treatment of anastomotic bleeding is meaningful. This paper investigates the reasons of anastomotic bleeding after laparoscopic anterior resection of rectal cancer, and introduces related preventions and treatments. Conservative treatment can be used first for small or delayed bleeding. As for acute bleeding from low anastomosis, transanal suture hemostasis can be considered. When the bleeding comes from high anastomosis and is massive and active, laparoscopic or open surgery must be performed immediately.


The use of growth hormone-releasing hormone in the diagnosis and treatment of short stature.
We have assessed the role of growth hormone-releasing hormone (GHRH) as a diagnostic test in 40 children and young adults with growth hormone deficiency (GHD), principally using the GHRH(1-29)NH2 analogue. Following 200 micrograms GHRH as an acute intravenous bolus, serum GH rose to normal or just subnormal levels in 13 out of 17 children with structural lesions, and in 8 of 14 patients with idiopathic GHD or panhypopituitarism. Of 9 children (mean age 12 years) with GHD following treatment with cranial irradiation for nonendocrine tumours, all responded acutely to GHRH. 12- and 24-hour infusions with GHRH(1-29)NH2, and 1- and 2-week treatments with twice-daily subcutaneous GHRH(1-29)NH2, showed persistent stimulation of GH release. It is concluded that many children with GHD of diverse aetiology will respond both acutely and chronically to treatment with GHRH.


Deterministic generation of a cluster state of entangled photons.
Photonic cluster states are a resource for quantum computation based solely on single-photon measurements. We use semiconductor quantum dots to deterministically generate long strings of polarization-entangled photons in a cluster state by periodic timed excitation of a precessing matter qubit. In each period, an entangled photon is added to the cluster state formed by the matter qubit and the previously emitted photons. In our prototype device, the qubit is the confined dark exciton, and it produces strings of hundreds of photons in which the entanglement persists over five sequential photons. The measured process map characterizing the device has a fidelity of 0.81 with that of an ideal device. Further feasible improvements of this device may reduce the resources needed for optical quantum information processing.


Monthly actuarial rates and monthly premium rate. Office of the Secretary. General notice.
This notice announces the monthly actuarial rates for aged (age 65 or over) and disabled (under age 65) enrollees in the Medicare. Supplementary Medical Insurance (SMI) program for the twelve months beginning July 1982. It also announces the monthly SMI premium rate to be paid by all enrollees during the twelve months beginning July 1982.


Metabolism of a bisphosphonate ester (PNU-91638) in rat.
1. Metabolites of the cyclic bisphosphonate ester, 4-[2,2'-bis-(5,5- dimethyl-1,3,2-dioxaphosphorinan-2-yl)] butanoyl-3-fluoro-benzene (PNU-91638) in bile or urine of the male Sprague-Dawley rat were characterized by mass spectrometry. The chronically bile duct/duodenal-cannulated male rats received a single oral dose of 100 mg/kg [13C] [14C]PNU-91638. Bile and urine samples were analysed for radioactivity and profiled by hplc with radiometric and UV detection. 2. The 0-28-h bile and urine accounted for 46.0 and 19.7% of dose respectively. The structures of radioactive peaks were investigated by ionspray and liquid secondary ion mass spectrometry (LSIMS) and LSIMS/MS analysis. 3. Major metabolites in urine included two regioisomeric phenol glucuronides, a gem methyl hydroxylated metabolite of the bisphosphonate heterocycle, a phenol metabolite, parent drug and a benzylic alcohol metabolite. Additional metabolites in bile included an unstable phenol/glutathione adduct (from a putative epoxide intermediate) with several minor isobaric regioisomers, and a carboxylic acid derived from the gem methyl hydroxylated bisphosphonate ring. 4. The structures proposed have not been confirmed by nmr due to discontinuation of the development of PNU-91638.


[New oxidized LDL receptors and their functions in atherogenesis].
Oxidized low density lipoprotein (Ox-LDL) appears to play key roles in atherosclerotic progression and plaque rupture. Biological effects of Ox-LDL on vascular cells may, at least in part, be mediated by cell surface receptors for Ox-LDL. Lectin-like oxidized LDL receptor (LOX)-1 and scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) are type II and I membrane glycoprtoeins, respectively, both of which can act as cell-surface endocytosis receptors for atherogenic oxidized LDL (Ox-LDL). LOX-1 expression can dynamically be induced by proinflammatory stimuli, and is detectable in cultured macrophages and activated vascular smooth muscle cells (VSMC), in addition to endothelial cells. LOX-1-dependent uptake of Ox-LDL induced apoptosis of cultured VSMC. In vivo, endothelial cells that cover early atherosclerotic lesions, and intimal macrophages and VSMC in advanced atherosclerotic plaques dominantly express LOX-1. LOX-1 expressed on the cellsurface can be cleaved, in part, and released as soluble molecules, suggesting the diagnostic significance of plasma soluble LOX-1 levels. SR-PSOX appeared to be identical to CXCL16, a novel membrane-anchored chemokine directed to CXCR6-positive lymphocytes, suggesting another role of SR-PSOX as T-cell chemoattractant. In contrast to LOX-1 expressed by a variety of cell types. SR-PSOX expression appeared relatively confined to macrophages in atherogenesis. Taken together, LOX-1 and SR-PSOX may play important roles in atherogenesis and athrosclerotic plaque rupture.


Feasibility of laparoscopic resection for perforated diverticulitis: a retrospective observational study of 77 consecutive patients.
Perforated colonic diverticulitis with purulent or fecal contamination (PCD) is a surgical emergency with high morbidity and mortality. Traditionally, open surgery as a Hartmann procedure (HP) has been performed. Feasibility of the laparoscopic approach (LA) either with primary anastomosis (PA) or as an HP has been shown, but evidence and implementation into daily routine remain low. We analysed all patients with PCD and emergency surgery at our institution to compare post-operative outcomes between LA and open surgery. Our results should add more evidence about the potential benefit of LA in treating PCD. This retrospective analysis conducted at a tertiary care centre in Germany included all patients with PCD undergoing emergency surgery between June 2007 and February 2019. Mortality and postoperative morbidity according to Clavien-Dindo-Classification are the primary endpoints. Secondary endpoints were stoma-free survival and length of hospital stay. Seventy-seven patients were identified (41 female/36 male; median age 67.9 years). Sixty patients underwent a LA (conversion in 9 of 60, 15%). PA has been performed in 25 of 77 patients (22 LA, 3 with open surgery). Severe complications and death (Clavien-Dindo-Classification grade IIIb-V) were lower in patients with LA (17/60, 28%) compared to open surgery (9/17, 53%; p = 0.082) as well as the length of hospital stay (LOS; LA 9 days vs. open surgery 17 days; p = 0.016). The LA is feasible in the majority of patients with PCD and may be warranted as a routine in emergency surgery. Although limited by a selection bias of this retrospective study, the LA seems to reduce morbidity and LOS.


Survival of Suspension-cultured Sycamore Cells Cooled to the Temperature of Liquid Nitrogen.
Suspension-cultured cells of sycamore (Acer pseudoplatanus L.) which were immersed in liquid nitrogen after prefreezing to the temperatures from -30 to -50 C in the presence of dimethylsulfoxide and glucose as cryoprotective additive could proliferate vigorously when rewarmed rapidly in water at 40 C. For maintaining high viability of the cells after immersion in liquid nitrogen, it seems to be essential to use the cells at the later lag phase or the early cell division phase. This study provides a possibility for long term preservation in liquid nitrogen of plant-cultured lines.


Present status and future directions: Surgical extrusion, intentional replantation and tooth autotransplantation.
Surgical extrusion, intentional replantation and tooth autotransplantation procedures are important treatment options that clinicians may consider performing in their day-to-day clinical practice. Despite compromised teeth are generally considered for extraction, clinicians must be aware that these cases could be suitable for management by these alternative predictable treatment options. Surgical extrusion, intentional replantation or tooth autotransplantation have similar treatment protocols which includes atraumatic tooth extraction, visualisation of the root portion and replantation. Surgical extrusion is defined as the 'procedure in which the remaining tooth structure is repositioned at a more coronal/supragingival position in the same socket in which the tooth was located originally'. Intentional replantation is defined as the 'deliberate extraction of a tooth and after evaluation of root surfaces, endodontic manipulation and repair, placement of the tooth back into its original position'. Tooth autotransplantation is defined as the 'transplantation of an unerupted or erupted tooth in the same individual, from one site to another extraction site or a new surgically prepared socket'. The same team previously published a narrative review (International Endodontic Journal. 2020, 53, 1636) and European Society of Endodontology position statement (International Endodontic Journal. 2020, 54, 655) on this topic in International Endodontic Journal. The aim of the current updated review was to provide the reader a complete overview and background on these procedures, to established clear clinical protocols and step-by-step for technically perform these therapies in their clinical practice and to establish future directions on the topics. The clinicians must periodically update their knowledge about these three procedures to achieve success.


Parents' socialization of children's injury prevention: description and some initial parameters.
In a year-long participant observation study of remediative action following actual injury, 61 8- and 9-year-old children and their 27-46-year-old mothers wrote records and reported on more than 1,000 minor injuries in branching biweekly interviews. Mothers reported that 80.1% of injuries received no parent-initiated remediation, 14% received only a lecture, and less than 3% of injuries were followed by parental action. Children reported that 96.1% of their injuries were followed by no remediative action and recalled lectures after only 1.2% of injuries. Remediative action was related to type of child activity (e.g., unstructured play was followed by remediation more often than more purposive behavior) and to mother's affect (e.g., anger) and beliefs (e.g., that injury was the child's fault or due to rule violation). The parameters that influenced remediative consequences, and thus that may influence future injury, are discussed.


Thrombopoietin Measurement as a Key Component in the Evaluation of Pediatric Thrombocytosis.
JAK2, MPL, and CALR mutations, which underlie essential thrombocythemia (ET) in most adults, are infrequent in children. Consequently, additional tests are needed to confirm pediatric ET diagnoses. We report a child with suspected ET and normal JAK2, MPL, and CALR analyses. Serum thrombopoietin (TPO) was markedly elevated, leading to analysis of the TPO gene, TPHO, which contains an upstream open reading frame (uORF) known to repress THPO translation. Sequencing revealed a de novo, germline stopgain mutation in the uORF, explaining the elevated TPO and thrombocytosis. This finding suggests that screening TPO levels and, if elevated, THPO 5' UTR sequencing could be diagnostic.


Comparative Studies of the Thylakoid Proteins of Mesophyll and Bundle Sheath Plastids of Zea mays.
The proteins from both grana and stroma lamellae of maize (Zea mays) mesophyll plastids and from maize bundle sheath plastid membranes have been compared by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels using a discontinuous buffer system. Peptide differences between grana and stroma lamellae were essentially quantitative and not qualitative. Bundle sheath plastid membrane peptides more closely resembled those of the ultrastructurally similar stroma lamellae. However, bundle sheath membranes contained several peptides not apparent in the stroma lamellae.The unappressed membranes (stroma lamellae and bundle sheath plastid membranes) were enriched in heavy (60-40 kilodaltons) peptides and depleted in light (31-20 kilodaltons) peptides as compared to stacked grana membranes. The heavier peptides were tentatively identified as subunits of chloroplast coupling factor. These peptides in unappressed membranes were much more resistant to removal by washing with ethylenediaminetetraacetate (under conditions of low ionic strength) than they were in granal membranes.Ribulose-1,5-diphosphate carboxylase was identified on the gels and was localized exclusively in the bundle sheath cells. It is suggested that sodium dodecyl sulfate electrophoresis is a simple method to test for the localization of carboxylase in various C(4) plastid fractions.


Quercetin Impairs HuR-Driven Progression and Migration of Triple Negative Breast Cancer (TNBC) Cells.
In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients (p = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., β-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-β-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.


Incidence and mortality of relapsing polychondritis in the UK: a population-based cohort study.
Relapsing polychondritis is a rare disease characterized by cartilage inflammation. Our aim was to estimate the incidence, prevalence and mortality of relapsing polychondritis and describe the clinical features of relapsing polychondritis in a large population. All participants diagnosed with relapsing polychondritis were sampled from the Clinical Practice Research Datalink. Prevalence and incidence rates for 1990-2012 were estimated. Relative mortality rates were estimated in a time-to-event framework using reference UK life tables. A questionnaire validation study assessed diagnostic accuracy. There were 117 participants with relapsing polychondritis ever recorded. Fifty (82%) of 61 cases were validated by a physician and unconfirmed cases were excluded. The analysis included 106 participants (42 men, 64 women) diagnosed with relapsing polychondritis. The mean age (range) at diagnosis in men was 55 (range 17-81) years and in women 51 (range 11-79) years. The median interval from first symptom to diagnosis was 1.9 years. The incidence of relapsing polychondritis between 1990 and 2012 was 0.71 (95% CI 0.55, 0.91) per million population per year. There were 19 deaths from any cause. There were 16 observed deaths eligible for survival analysis and 7.4 deaths expected for the UK population of the same age, sex and period. The standardized mortality ratio was 2.16 (95% CI 1.24, 3.51), P < 0.01. Respiratory disease, cardiac conditions and cancer were the most frequent causes of death. The incidence of relapsing polychondritis may be lower than previously estimated, and diagnostic misclassification and delay are common. Mortality in relapsing polychondritis is more than twice that of the general population.


Continuity and change in Canada's unemployment-immigration linkage (1946-1993).
"Between 1946 and 1976, variation in unemployment rates strongly affected the number of immigrants allowed into Canada. Implementation of the Immigration Act of 1976 should have weakened the effect of unemployment on immigration, for the Act requires that immigration levels be set after consideration of demographic as well as labour market conditions. Our analysis shows the unemployment-immigration linkage actually strengthened after 1978, and only weakened significantly after 1989. Since the government's annual immigration projections are excellent predictors of immigration landings, we conclude the Canadian state is highly capable of controlling immigration levels and thus the tightening of the unemployment-immigration linkage from 1978 to 1989 reflected the choice of regulators. Discussing future research in this area, we argue that if the immigration policymaking process was not restructured in the late 1980s, an adequate model of state-society relations in this area must account for both continuity and change. However, if the process was restructured, a revised or new theoretical framework is needed." (SUMMARY IN FRE)


Moyamoya syndrome after radiation therapy: case reports.
Potentially harmful effects of irradiation on the developing central nervous system have been well documented. We report 2 pediatric patients with moyamoya syndrome developed after irradiation. A 3-year-old girl had received 4,860 cGy of postoperative radiation for optic pathway glioma. Cerebral angiography 7 months after completion of the radiation therapy revealed progressive cerebral arterial occlusive disease, involving the internal carotid artery on either side of the circle of Willis, with abnormal netlike vessels. Another 5-year-old girl had received 3,600 cGy of postoperative radiation on the cerebrum for a medulloblastoma. Two years later, she was diagnosed with moyamoya syndrome and treated with indirect revascularization. She died due to further progressive obstruction of the right M1 and A1 on the unoperated hemisphere, in spite of well-developed collateral circulation from the superficial temporal artery and middle meningeal artery on the operated left hemisphere. We suggest that radiation therapy with portals typically including carotid siphon may particularly cause vascular damage, regardless of the tumor pathology and lead to radiation-induced moyamoya syndrome. The prognosis may be poorer in case of poor collateral flow and rapid progression. The radiation therapy may cause fatal vascular damage so it should be taken into consideration when a treatment plan is being formulated for young patients.


Increased expression of human thioredoxin/adult T cell leukemia-derived factor in Sjögren's syndrome.
To determine the involvement of human thioredoxin/adult T cell leukemia-derived factor TRX/ADF) in Sjögren's syndrome (SS) and the correlation with Epstein-Barr virus (EBV). Indirect immunohistochemical techniques and reverse transcriptase polymerase chain reaction were utilized to analyze TRX/ADF expression and the presence of EBV, using 6 normal tissues and 23 surgical specimens. The kinetics of expression of TRX/ADF induced by EBV was examined in vitro with peripheral blood B cells from EBV-seronegative donors. Marked expression of TRX/ADF was found in the infiltrating B cells and the epithelial cells of salivary gland tissues from patients with SS (11 of 12 cases), but not in those from patients with other salivary gland inflammatory conditions (0 of 11 cases) or those of normal individuals (0 of 6 cases). In immunohistologic analyses, a striking topographic correlation between TRX/ADF and EBV was found. The coexistence of TRX/ADF messenger RNA and EBV DNA was detected by polymerase chain reaction (r = 0.75, P < 0.01). Peripheral blood B cells from EBV-seronegative donors showed de novo synthesis of TRX/ADF following in vitro infection with EBV. EBV-infected B cell lines all expressed TRX/ADF. TRX/ADF was not detected in non-EBV-infected cells. Tumors in SCID mice reconstituted with mononuclear cells of salivary glands from SS patients, which were composed of human B cells carrying EBV DNA, were positive for TRX/ADF. These findings suggest that TRX/ADF expression closely reflects the intracellular event of EBV reactivation in SS. This is also the first report to show the ectopic in vivo expression of TRX/ADF in human autoimmune disease.


Underdetection of Interstitial Lung Disease in Juvenile Systemic Sclerosis.
Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.


Circular RNAs and glioblastoma multiforme: focus on molecular mechanisms.
Glioblastoma multiforme (GBM), as a deadly and almost incurable brain cancer, is the most invasive form of CNS tumors that affects both children and adult population. It accounts for approximately half of all primary brain tumors. Despite the remarkable advances in neurosurgery, radiotherapy, and chemotherapeutic approaches, cell heterogeneity and numerous genetic alterations in cell cycle control, cell growth, apoptosis, and cell invasion, result in an undesirable resistance to therapeutic strategies; thereby, the median survival duration for GBM patients is unfortunately still less than two years. Identifying new therapeutics and employing the combination therapies may be considered as wonderful strategies against the GBM. In this regard, circular RNAs (circRNAs), as tumor inhibiting and/or stimulating RNA molecules, can regulate the cancer-developing processes, including cell proliferation, cell apoptosis, invasion, and chemoresistance. Hereupon, these molecules have been introduced as potentially effective therapeutic targets to defeat GBM. The current study aims to investigate the fundamental molecular and cellular mechanisms in association with circRNAs involved in GBM pathogenesis. Among multiple mechanisms, the PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK signaling, angiogenic processes, and metastatic pathways will be thoroughly discussed to provide a comprehensive understanding of the role of circRNAs in pathophysiology of GBM. Video Abstract.


Relationship between acquired spastic talipes equinovarus and dystonia musculorum deformans.
Acquired spastic talipes equinovarus associated with dystonia musculorum deformans (DMD) presents orthopaedic surgeons with a difficult treatment problem. We reviewed the natural history, diagnostic evaluation, and treatment of this deformity in 12 patients. Two patients initially had the generalized form of dystonia, and 10 patients had the focal form (in which acquired spastic talipes equinovarus was the only manifestation). With time, five of these 10 developed the generalized form. A positive family history and age < 14 years at onset were prognostic of this progression.


Design and characterization of tissue-specific extracellular matrix-derived microcarriers.
The three-dimensional (3D) extracellular matrix (ECM) environment plays a critical role in mediating normal cellular behavior and tissue organization. While commercially available microcarriers have shown promise, limited research has been conducted on the design of tissue-specific, custom-fabricated microcarriers, engineered to mimic the composition of the native ECM of cells or tissues of interest. Moving toward this goal, methods were developed to fabricate microcarriers from decellularized adipose tissue (DAT) via minimally-cytotoxic protocols. Characterization by microscopy confirmed the production of stable spherical microcarriers, with a microporous surface topography and porous interior. The mean diameter of the DAT microcarriers was 934±51 μm, while the porosity was estimated as 29%±4% using liquid displacement. Stability and swelling behavior over 4 weeks indicated that the DAT microcarriers were effectively stabilized with the photochemical crosslinking agent rose bengal, with total protein release in a simulated physiological environment remaining below 10 μg/mL at all time points. Preliminary cell culture studies with human adipose-derived stem cells (ASCs) in a spinner flask system indicated enhanced cell attachment and proliferation of ASCs on DAT microcarriers over 14 days, as compared with gelatin control microcarriers fabricated using similar methods. Testing confirmed injectability of the DAT microcarriers, further supporting the clinical potential of the approach for localized cell delivery and small volume augmentation in plastic and reconstructive surgery. Overall, tissue-specific microcarriers prepared from solubilized DAT were found to be highly supportive of human ASCs cultured in a 3D dynamic environment.


Growth hormone treatment in non-growth hormone-deficient children: effects of stopping treatment.
Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved GH levels greater than 15 mU/l following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase, demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period, all children received GH according to the same dose regimen; they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating 'catch-down' growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.


Low-flow anesthesia and reduced animal size increase carboxyhemoglobin levels in swine during desflurane and isoflurane breakdown in dried soda lime.
After institutional approval, we studied the effect of animal size, anesthetic concentration, and fresh gas flow (FGF) rate on inspired carbon monoxide (CO) and carboxyhemoglobin (COHb) during anesthesia in swine, using soda lime previously dried to 1 +/- 0.1% water content. To ascertain the effect of anesthesia, eight adult pigs were anesthetized with either 1 minimum alveolar anesthetic concentration (MAC) desflurane or isoflurane and, to characterize the effect of the FGF rate, it was doubled in four pigs. To determine the effect of animal size, four small and four large pigs received 1 MAC desflurane or isoflurane, and to determine the effect of the anesthetic concentration, a group of four swine was exposed to 0.5 MAC. CO and COHb concentrations were larger with desflurane (5500 +/- 980 ppm and 57.90% +/- 0.50%, respectively) than with isoflurane (800 ppm and 17.8% +/- 2.14%, respectively), especially in the small animals. Increasing the FGF rate significantly reduced peak CO and COHb concentrations resulting from both anesthetics; however, when each anesthetic was reduced to 0.5 MAC, the concentrations obtained were similar. We conclude that CO intoxication is more severe with desflurane than with isoflurane, that small animals are at higher risk for CO poisoning, and that low FGF can increase COHb concentrations. The present study shows that the use of desflurane with desiccated carbon dioxide absorbents in pediatric anesthesia can produce a dangerous carbon dioxide intoxication, especially with low-flow anesthesia.