Tetanus immunity after diphtheria, tetanus toxoids, and acellular pertussis vaccination in children with clinically stable HIV infection.
HIV infection often impairs the immune response to childhood vaccines. We sought to study the ability of HIV-infected children receiving highly active antiretroviral therapy (HAART) to generate a booster response to immunization with a recall antigen to which they had lost humoral immunity. Diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccination was given at either 16 or 36 weeks after initiation of HAART to 37 HIV-infected children 2 to 9 years of age with a history of DTaP or diphtheria-tetanus-pertussis receipt who had negative tetanus antibody titers (<or=1:243) at baseline. There was a clear increase in tetanus titers after vaccination, with an increase of 27-fold over the baseline values at weeks 4 and 8. The effect on tetanus titers faded to a 9-fold and 3-fold increase over baseline values at weeks 18 and 32, respectively. DTaP vaccination did not affect HIV-1 RNA viral load or CD4 percentage or cell count. There was no increase in either acute or long-term adverse events associated with the DTaP vaccination. Although children with stable HIV infection receiving HAART can mount antigen-specific responses to tetanus immunization, the durability of these responses might be limited. Long-term monitoring of specific immune function in such children is indicated.


Recovery of rainbow trout olfactory function following exposure to copper nanoparticles and copper ions.
In response to environmental information received by olfactory sensory neurons (OSNs), fish display different behaviors that are crucial for reproduction and survival. Damage to OSNs from direct exposure to environmental contaminants can disrupt fish olfaction. Copper nanoparticles (CuNPs) are neurotoxic contaminants which can impair fish olfactory function. However, it is uncertain if CuNP-induced olfactory dysfunction is reversible. Here, we compared the recovery of rainbow trout olfactory mucosa after being exposed to CuNPs or dissolved copper (Cu2+). Following a 96 h exposure to CuNPs or Cu2+, recovery was tested 14 min and 7 days after exposure using electro-olfactography (EOG). Results indicated the 14 min recovery period was not sufficient to improve the olfactory sensitivity in either Cu treatment. After 7 days of transition to clean water, olfactory mucosa was able to recover from Cu2+-induced dysfunction, while no recovery was observed in the CuNP-exposed OSNs. This olfactory dysfunction in the CuNP treatment was observed when no Cu was significantly accumulated in the olfactory mucosa after the recovery period. The transcript abundances of a subset of genes involved in olfactory signal transduction (OST) were downregulated in the CuNP-exposed fish after the 7-day recovery period. These results revealed that odorant reception through OST cascade remained impaired over the recovery period in the CuNP-treated OSNs. The ion regulation gene transcripts were not dysregulated in either Cu treatment, which suggests that neural ion balance was not affected following the recovery period. Collectively, our findings revealed the CuNP-induced olfactory dysfunction was irreversible after the 7-day recovery period. Given the importance of olfaction in crucial aspects of fish life, it is likely that the CuNP-induced impairment of odorant reception pose risks to the survival of fish.


Sunitinib dose-escalation after disease progression in metastatic renal cell carcinoma.
Previous pharmacologic studies demonstrated that higher sunitinib exposure is associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). We aimed to assess the efficacy and toxicity of sunitinib dose-escalation in mRCC patients progressing on the standard 50mg dose. A single-institution retrospective review was conducted on mRCC patients, treated outside trials with a 50mg sunitinib dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging. All progressing patients who were dose-escalated to 62.5 and 75mg on an individualized schedule if toxicity permitted were eligible for this analysis. Median progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. PFS1 and 2 were defined as the time between the start of sunitinib and first progression and the time between dose-escalation and second progression respectively. A total of 25 eligible patients were identified with a median follow-up of 40.3 months (Q1-Q3: 11.1-66.6) and a mean age of 54 years (standard deviation: 12.4). Most of the patients underwent cytoreductive surgery (92%) and were men (88%). In total 32%, 44%, and 24% had a good, intermediate, and poor prognostic Heng Score, respectively. At standard doses, 60% and 16% of patients had a partial response (PR) and a stable disease (SD) as best response respectively for a median duration of 11.4 months (95% CI: 3-20.7). A total of 6 patients (24%) had progressive disease as best response. After progression, 36% and 28% had PR and SD on higher doses of sunitinib respectively for a median duration of 7.8 months (95% CI: 6.3-12.4). The median PFS1, PFS2 and OS were 6.1 months (95% CI: 2.3-19.4), 6.7 months (95% CI: 3.1-8.4) and 63.7 months (95% CI: 26-NR) respectively. The most common adverse events after dose-escalation were fatigue (56%), diarrhea (40%) and skin toxicity (28%). Patients with mRCC who progress on 50mg sunitinib dose, may derive a clinical benefit and prolonged survival from dose-escalation with acceptable toxicity profiles. These results need to be confirmed in prospective studies with the aim to overcome drug resistance and delay the change in systemic therapy at progression.


Performance evaluation of the CellaVision DM96 system: WBC differentials by automated digital image analysis supported by an artificial neural network.
We evaluated the CellaVision DM96 (CellaVision AB, Lund, Sweden), an automated digital cell morphology and informatics system for peripheral blood smears. Technologists agreed with 82% of the instrument's preclassifications. Correlation coefficients between final results released from the CellaVision and results obtained by direct microscopy were 0.96 (all neutrophils), 0.94 (lymphocytes), 0.88 (segmented neutrophils), 0.73 (eosinophils), 0.69 (bands), and 0.67 (monocytes). After correction for statistically and clinically insignificant variations, the CellaVision DM96 had 95% sensitivity and 88% specificity for immature myeloid cells. It was 100% sensitive and 94% specific for blasts, and 100% sensitive and 97% specific for unusual WBCs and nucleated RBCs. Advantages of the CellaVision DM96 over direct microscopy include the ability to review slides from a remote location, consultation and quality control on a cell-by-cell basis, and potential labor savings.


Synthesis and biological evaluation of triterpenoid thiazoles derived from betulonic acid, dihydrobetulonic acid, and ursonic acid.
In this work, 35 new derivatives of betulonic, dihydrobetulonic and ursonic acid were prepared including 30 aminothiazoles and all of them were tested for their in vitro cytotoxic activity in eight cancer cell lines and two non-cancer fibroblasts. Compounds with the IC50 below 5 μM in CCRF-CEM cells and low toxicity in non-cancer fibroblasts (4m, 5c, 5m, 6c, 6m, 7b, and 7c) were further subjected to tests of pharmacological parameters yielding the final set for advanced biological evaluation (4m, 5m, 6m, and 7b). It was proved by several methods, that all of them trigger apoptosis via the intrinsic pathway and derivatives 5m and 7b are the most effective (IC50 2.4 μM and 3.6 μM). They are the best candidates to become potentially new anticancer drugs and will be subjected to in vivo tests in mice. In addition, compounds 6b and 6c deserve more attention because their activity is not limited only to chemosensitive CCRF-CEM cell line. Specifically, compound 6b is highly active against K562 leukemic cell line (0.7 μM) and its IC50 activity in colon cancer HCT116 cell line is 1.0 μM. Compound 6c is active in both normal K562 and resistant K562-TAX cell lines (IC50 3.4 μM and 5.4 μM) and both colon cancer cell lines (HCT116 and HCT116p53-/-, IC50 3.5 μM and 3.4 μM).


Postfunctionalization of polyoxometalates: an efficient strategy to construct organic-inorganic zwitterions.
A class of monoorganoimido-substituted hexamolybdates containing a pyridine group have been firstly synthesized. Furthermore, a reaction protocol of alkylation based on the resulting pyridine-functionalized hexamolybdates has been developed, with which a type of zwitterionic clusters has been successfully obtained.


Classes of neurons in relation to the laminar organization of the lateral geniculate nucleus in the tree shrew, Tupaia belangeri.
We used the rapid Golgi and horseradish peroxidase (HRP) techniques to study the dendritic spread of relay neurons in functionally distinct laminae of the tree shrew dorsal lateral geniculate nucleus (LGNd). On the basis of their dendritic spread in relation to laminar and interlaminar zones, we describe three classes of relay neurons. Unilaminar neurons with multipolar radiate, bitufted, and intermediate types of dendrites. Dendrites of these neurons are confined to one lamina only, but also can have some of their segments in adjacent interlaminar zones. Multilaminar neurons with multipolar radiate, bitufted, and intermediate types of dendrites. Independent of the site of their cell bodies in a laminar or interlaminar zone, these neurons spread their dendrites over two or more laminae. Interlaminar neurons whose cell bodies and dendrites are confined to a single interlaminar zone. Unilaminar neurons are found in all the laminae. In the medial three laminae, they are more of the radiate type, whereas in laminae 4 and 5 their dendrites tend to be more of a tufted nature. Lamina 6 shows a preponderance of the elongated bitufted type. Multilaminar neurons, although less common as compared to the unilaminar, are also observed in all the laminae. Some neurons have their dendrites confined to an interlaminar zone. By retrograde transport of HRP injected into the visual cortex, we have shown that these neurons are, in fact, relay neurons. In addition to relay neurons, there are small interneurons with "axoniform" dendrites and an unmyelinated axon whose arborization is confined within the limits of the neuron's dendritic spread. Neurons of this type are not labeled with HRP injected into the visual cortex. We conclude that although each lamina is functionally specialized by input from ipsilateral or contralateral retina and by segregation of neurons responding to on or off stimuli, some multilaminar neurons can be found in each lamina. Thus, laminar as well as interlaminar zones contain a class of neurons that could provide a cross-talk between the functionally specialized laminae. Most relay neurons in all the laminae, however, confine their dendrites to their home lamina. Thus, the dendritic architecture of relay neurons allows for processing of information both within channels and between channels.


Use of nonsteroidal anti-inflammatory drugs and poor olfaction in women.
It is unclear whether regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with poor olfaction in older adults. We selected 4020 participants, aged 50 to 79 years in 2018, from 36,492 eligible participants in the National Institute of Environmental Health Sciences Sister Study, according to their self-reported olfaction status. Of these, 3406 women completed the 12-item Brief Smell Identification Test. We defined poor olfaction as a test score ≤9 in the primary analysis. We then estimated odds ratios (ORs) and 95% confidence intervals (CIs) from weighted logistic models, accounting for the study design, missing exposures/outcomes, and covariates. Overall, NSAID use was not associated with poor olfaction. However, we found evidence for potential multiplicative interactions. Specifically, the OR comparing regular versus never use of aspirin was 1.8 (95% CI, 1.1-3.2) among women who had not regularly used nonaspirin NSAIDs, while the corresponding OR was 0.8 (95% CI, 0.5-1.2) among nonaspirin NSAID users (P for interaction = 0.016). Similar results were seen for ibuprofen alone versus ibuprofen with other NSAID use (P for interaction = 0.010). Among women using either drug alone, associations with poor olfaction increased with increasing duration and cumulative dose. Post hoc analyses showed that the interactions could not be readily explained by potential biases. Other NSAIDs were not associated with olfaction. Long-term regular use of aspirin or ibuprofen was associated with poor olfaction among women who never regularly used other types of NSAIDs. These preliminary findings warrant independent confirmation.


Unmasking the suppressed immunopeptidome of EZH2-mutated diffuse large B-cell lymphomas through combination drug treatment.
Exploring the repertoire of peptides presented on major histocompatibility complexes (MHCs) helps identify targets for immunotherapy in many hematologic malignancies. However, there is a paucity of such data for diffuse large B-cell lymphomas (DLBCLs), which might be explained by the profound downregulation of MHC expression in many DLBCLs, and in particular in the enhancer of zeste homolog 2 (EZH2)-mutated subgroup. Epigenetic drug treatment, especially in the context of interferon-γ (IFN-γ), restored MHC expression in DLBCL. In DLBCL, peptides presented on MHCs were identified via mass spectrometry after treatment with tazemetostat or decitabine alone or in combination with IFN-γ. Such treatment synergistically increased the expression of MHC class I surface proteins up to 50-fold and the expression of class II surface proteins up to threefold. Peptides presented on MHCs increased to a similar extent for both class I and class II MHCs. Overall, these treatments restored the diversity of the immunopeptidome to levels described in healthy B cells for 2 of 3 cell lines and allowed the systematic search for new targets for immunotherapy. Consequently, we identified multiple MHC ligands from the regulator of G protein signaling 13 (RGS13) and E2F transcription factor 8 (E2F8) on different MHC alleles, none of which have been described in healthy tissues and therefore represent tumor-specific MHC ligands that are unmasked only after drug treatment. Overall, our results show that EZH2 inhibition in combination with decitabine and IFN-γ can expand the repertoire of MHC ligands presented on DLBCLs by revealing suppressed epitopes, thus allowing the systematic analysis and identification of new potential immunotherapy targets.


Cold and immobilization stress-induced changes in pain responsiveness and brain Met-enkephalin-like immunoreactivity in the rat.
Pain responsiveness and Met-enkephalin-like immunoreactivity (MLI) were studied in the rat after cold (25 degrees C) and immobilization stress for different lengths of time (30 min, 90 min and 180 min). The 30-min stress-induced analgesia (as measured by the tail-flick method), which was partially antagonized by pretreatment with naloxone (5 mg/kg, SC), and the magnitude of this analgesia was less than that of the 90-min stress or 180-min stress. The 30-min stress resulted in a significant decrease in MLI in the mesolimbic area, striatum, hypothalamus and thalamus. After the 90-min stress, MLI was found to be significantly decreased in the prefrontal cortex, amygdaloid nuclei and piriform cortex, thalamus and hippocampus, while the 180-min stress failed to induce a significant change in any brain area tested. As such a change in MLI content was thought to be related to an increase in the activity of the endogenous Met-enkephalin neuronal system, the activation of this system by the stress, especially in the hypothalamus and thalamus, seemed to be associated with analgesia.


Chemotherapy-induced thrombocytopenia in Ewing sarcoma: Implications and potential for romiplostim supportive care.
Maintaining dose-dense, interval-compressed chemotherapy improves survival in patients with Ewing sarcoma but is limited by myelosuppression. Romiplostim is a thrombopoietin receptor agonist that may be useful in the treatment of chemotherapy-induced thrombocytopenia (CIT). Patients aged between 3 and 33 years with Ewing sarcoma from 2010 to 2020 were reviewed. CIT was defined as a failure to achieve 75,000 platelets per microliter by day 21 after the start of any chemotherapy cycle. Fisher's exact test was used for univariate analysis and Pearson's correlation coefficient was used for the association between continuous variables. Twenty-seven out of 42 patients (64%) developed isolated CIT, delaying one to four chemotherapy cycles per patient. CIT occurred during consolidation therapy in 24/27(88.9%) and with ifosfamide/etoposide cycles in 24/27 (88.9%). Univariate analysis failed to identify risk factors for CIT. The use of radiation approached significance (p-value = .056). Ten patients received romiplostim. The median starting dose was 3 μg/kg (range 1-5). Doses were escalated weekly by 1-2 to 4-10 μg/kg and continued throughout chemotherapy. A higher romiplostim dose was associated with a higher change in average platelet counts from baseline, r = .73 (p = .04). No romiplostim-related adverse events were identified aside from mild headache. CIT is the primary reason for the inability to maintain treatment intensity in Ewing sarcoma. The concurrent use of romiplostim with chemotherapy was safe and feasible, and efficacy was associated with higher romiplostim doses.


The surgical treatment of low back pain.
If nonoperative management fails to relieve a clearly identifiable and surgically treatable cause of lumbar pain, then surgery may be beneficial. Certain "red flags" indicate the need for urgent or emergent surgical intervention. Low back pain is associated with several degenerative conditions in the lumbar spine, including degenerative disc disease, spinal stenosis, spondylolisthesis, degenerative scoliosis, facet joint syndrome, and disc herniation.


New approach for T-wave end detection on electrocardiogram: performance in noisy conditions.
The detection of T-wave end points on electrocardiogram (ECG) is a basic procedure for ECG processing and analysis. Several methods have been proposed and tested, featuring high accuracy and percentages of correct detection. Nevertheless, their performance in noisy conditions remains an open problem. A new approach and algorithm for T-wave end location based on the computation of Trapezium's areas is proposed and validated (in terms of accuracy and repeatability), using signals from the Physionet QT Database. The performance of the proposed algorithm in noisy conditions has been tested and compared with one of the most used approaches for estimating the T-wave end point: the method based on the threshold on the first derivative. The results indicated that the proposed approach based on Trapezium's areas outperformed the baseline method with respect to accuracy and repeatability. Also, the proposed method is more robust to wideband noise. The trapezium-based approach has a good performance in noisy conditions and does not rely on any empirical threshold. It is very adequate for use in scenarios where the levels of broadband noise are significant.


The measurement of stress-inducing life events and life styles: questions of conceptual independence and discriminant validity.
Research on psycho-social sources of coronary heart disease (CHD) has focused on two basic ideas: on the one hand that CHD is the result of the accumulation of stress-inducing events and, on the other hand, that CHD stems from the way in which individuals live their lives and respond to events that do occur. While it is relatively easy to separate these ideas at the conceptual level, the research reported here indicates that the two most prominent operationalizations of life situation and life style share some degree of commonality in their domains. Specifically, a comparison of the responses of 205 individuals indicate that variations in scores on the Jenkins Activity Survey are associated with variations in scores on subjective but not objective items on the Recent Life Changes Questionnaire. The implications of these results for the study of psycho-social factors in CHD are discussed.


Hypopituitary patients prefer a touch-screen to paper quality of life questionnaire.
Health Related Quality of Life questionnaires are frequently used for research, however only recently has their use been recommended in the routine clinical management of pituitary patients. Questionnaires frequently have complex scoring systems, and may be cumbersome, limiting widespread application. Touch-screen technology can overcome these limitations. We have developed a touch-screen 'Questions on Life Satisfaction-Hypopituitarism' QLS-H (Flash 5 Action script, program design by IG) questionnaire and compared its use and accuracy with a paper version questionnaire in 50 pituitary patients who were attending routine clinics. The HRQoL Z-score for the patient group was lower than the average for the normal UK population, as might be predicted for this patient group. There was no statistically significant difference between scores obtained by the touch-screen and paper questionnaires; mean (SD) Z score was -1.33 (1.4) for touch-screen and -1.26 (1.5) for paper. The touch-screen was preferred by 80% of patients, and quicker to complete (<5min). Additionally, there were significant errors in 14 (28%) of manually scored paper questionnaires. Touch-screen QLS-H questionnaires have advantages over the paper version for the routine clinical assessment of patients with hypopituitarism.


A novel technique for laser-assisted revascularization: an in vitro pilot study.
The common limitation of surgical revascularization procedures for severe tissue ischemia due to cardiovascular diseases is the need to interrupt blood flow during the intervention. We aim to introduce a new technique that allows a sutureless, non-occlusive revascularization. A 3-step technique was developed using rabbit's aorta to simulate a side-to-side anastomosis model. It enables the creation of a bypass circuit for revascularization. The first step was the soldering of 2 vessels in a side-to-side fashion based on the laser-assisted vascular anastomosis (LAVA) principle using a diode laser emitting irradiation at 810 nm with an albumin-based solder patch between them, followed by the creation of a channel within the patch using either a holmium-doped yttrium aluminum garnet laser (Ho:YAG) at λ = 2100 nm or a xenon-chloride excimer laser (XeCl) at λ = 308 nm. Thereby, a bypass circuit was created, thus allowing a non-ischemic revascularization. The system was deemed functional when a flow was observed across the anastomosis. The highest average tensile strength recorded after side-to-side LAVA using a diode laser power of 3.2 W for 60 s was 2278.6 ± 800 mN (n = 20). The Ho:YAG laser created the channels with less tension on the anastomosis than the excimer laser. Histological analysis showed limited thermal damage and good patch-tissue adaptation. The preliminary results of this feasibility study outline the foundations for an entirely sutureless laser-assisted revascularization procedure. The next studies will evaluate the rheological parameters across the bypass circuit to optimize the post-anastomotic flow.


Role of β-Adrenoceptors and L-Type Ca(2+)-Channels in the Mechanism of Reperfusion-Induced Heart Injury.
We studied the effects of β-adrenoceptor antagonists propranolol and nadolol and L-type Ca(2+)-channel blocker verapamil on cardiac reperfusion injury developed after 45-min coronary occlusion. The substances were injected intravenously 5 min before reperfusion. The results indicate that activation of β-adrenoceptors and opening of L-type Ca(2+)-channels promote the development of cardiac reperfusion injury, while blockage of β-adrenoceptors and/or L-type Ca(2+)-channels prevents reoxygenation-induced myocardial injury. Propranolol, nadolol, and verapamil can produce infraction-limiting effects after onset of ischemic heart injury.


Accuracy of Tokuhashi score system in predicting survival of lung cancer patients with vertebral metastasis.
Controversy exists in the accuracy of Tokuhashi score (TS) system in predicting survival of patients with vertebral metastasis, including vertebral metastases from primary lung cancer. To calculate the accuracy of the TS in predicting survival of lung cancer patients with vertebral metastasis and investigate which subgroup's survival is suitable for TS to predict, we conduct this retrospective study. From January 2008 to December 2013, 151 patients with vertebral metastases from primary lung cancer in our institute were included. The data were censored at December 2014. Patients were classified according to TS. The actual and predicted survivals were compared to calculate the accuracy rate. Spearman's correlation analysis was conducted to explore the relation between overall survival and TS. Cox regression was carried out to investigate potential factors affecting prognosis. Only 8.6 % (13 patients) actually followed the survivorship pattern as predicted by the TS. Spearman's correlation analysis demonstrated that actual overall survival correlated significantly with the TS. Cox model indicated that status of visceral metastases (i.e., none, involved with lung, involved with extrapulmonary organ) and response to first-time systemic therapy (effective or not) are associated significantly with overall survival. For patients with visceral metastases and progression to first-time systemic therapy simultaneously, predicted survival by TS and actual survival matched well. TS could only predict survival accurately in those with visceral metastases and disease progression to first-time systemic therapy simultaneously. Thus, it may not be a reliable tool to predict survival in lung cancer patients with vertebral metastasis. Status of visceral metastases and response to first-time systemic therapy should be added into TS system to increase validity and accuracy.


A Japanese case of de novo dominant dystrophic epidermolysis bullosa.
We report a Japanese case of dominant dystrophic epidermolysis bullosa with a de novo mutation in the triple-helical domain of the type VII collagen. Mutation detection revealed a glycine --> aspartic acid substitution at amino acid position 2012 in exon 73 (G2012D). This previously unreported mutation underlies a clinical phenotype of moderately severe, localized skin blistering.


Real-world performance of SARS-CoV-2 rapid antigen testing through the Alpha-, Delta- and Omicron-dominant waves of the COVID-19 pandemic.
Compared with reverse transcription polymerase chain reaction (RT-PCR), rapid antigen detection tests (RADTs) for SARS-CoV-2 diagnostics are faster, less expensive, but also less accurate. Performance of RADTs is context-specific and depends on disease prevalence. In this real-world study, we assessed impact of RADTs in an inpatient setting through the entire COVID-19 emergency phase. In this matched retrospective study, data on RT-PCR and RADT laboratory diagnoses of SARS-CoV-2 made between February 2020 and May 2023 in a large hospital were analyzed. To be included in the study, samples used for both RT-PCR and RADT had to be collected on the same day. Of 278,867 RT-PCR tests available, 13,321 same-day RADTs could be matched to RT-PCR. Over the entire period, RADT sensitivity and specificity were 76.4% and 99.4%, respectively. With the observed positivity rate of 9.4%, positive and negative predictive values were 92.7% and 97.6%, respectively. Compared with the periods dominated by the Alpha and Delta variants of concern, RADT accuracy was slightly lower during the Omicron phase. This real-world experience demonstrates that despite suboptimal sensitivity and some variation by predominant variants of concern and positivity prevalence, the use of RADTs is useful in hospital settings. Public health implications were discussed.


Yield of 24-hour esophageal pH and bilitec monitoring in patients with persisting symptoms on PPI therapy.
Current management algorithms propose pH monitoring under proton pump inhibitors (PPIs) in suspected gastroesophageal reflux disease (GERD) with insufficient treatment response, but recent observations challenge this approach because of its low yield. To perform an audit of the outcomes of pH monitoring under PPI therapy in our unit, and to study the yield of additional nonacid reflux monitoring. All pH monitoring studies under antireflux therapy since 1997, with or without simultaneous Bilitec monitoring, were analyzed. From 1997 to 2003, 347 patients (157 men, mean age 49.4 +/- 0.8 years) underwent pH studies on PPI therapy (28% half-, 67% full-, and 5% double-dose PPI) for persisting typical (53%) or atypical (75%) symptoms. In 184 patients, simultaneous Bilitec monitoring was performed. Esophageal pH monitoring on PPI was pathological in 105 (30%) patients. Pathological pH monitoring on PPI was associated with typical reflux symptoms (64 versus 52%, P = 0.03), and a higher prevalence of persisting esophagitis (54 versus 36%, P < 0.005) and of hiatal hernia (58 versus 27%, P < 0.005). Bilitec monitoring on PPI therapy was pathological in 114 (62%) patients, of which 74 (40%) had normal pH monitoring. Adding Bilitec increased the rate of abnormal results over pH monitoring alone, from 38% to 69% on half-dose, from 27% to 69% on full-dose, and from 0% to 38% on double-dose PPI. The rate of abnormal pH monitoring in symptomatic GERD patients while on PPI therapy is relatively low, especially in those on double-dose PPI. Combined pH and Bilitec monitoring significantly increased the rate of ongoing pathological reflux compared to pH alone in refractory to PPI therapy GERD patients.


COVID-19 Vaccine Decision-Making Among Black Pregnant and Postpartum Women.
The history of biomedical research is marred by racially discriminatory and abusive practices that impacted Black/African Americans. Medical racism impacts the trust and utilization of new medical interventions, such as the COVID-19 vaccine. This study aimed to understand Black pregnant and postpartum women's perspectives and decision-making about the COVID-19 vaccine. We used a qualitative descriptive design and recruited 23 pregnant and postpartum Black women aged 18 years and above. Data was collected using a semi-structured interview guide. Data were analyzed using content analysis. The participants described factors influencing their decision to receive or not receive the COVID-19 vaccines. These factors included individual, cultural, ethnicity, religious, and family-related factors (individual-personal beliefs influenced decisions about the vaccine; ethnicity, culture, and religion influenced vaccine decision-making; group-family and friends played a role in decision-making), vaccine or vaccination-related issues (concerns about vaccination and pregnancy outcomes and mistrust in the vaccine information), and contextual influence (sources of vaccine information influenced decision-making and healthcare providers influenced decision-making). Understanding the vaccine decision-making process of underserved populations likely to decline vaccination due to pregnancy, postpartum, and breastfeeding status will help design tailored interventions to improve vaccine acceptance in minority communities, especially for pregnant and postpartum women.


Polybrominated diphenyl ethers in leaves and soil from typical electronic waste polluted area in South China.
Polybrominated diphenyl ethers (PBDEs) in leaves and soil from typical e-waste polluted area in South China were investigated. The concentrations (ng/g dry weight) of PBDE congeners and summation operatorPBDE of five leaf samples were much lower than those in soil sample. The general patterns of summation di-BDEs to summation hepta-BDEs percentage distribution in leaf samples were similar to those of the soil sample, except the percentage of BDE209 which were lower than in soil. The percentages of summation di-BDEs to summation hepta-BDEs in soil were in the range of those in leaf samples. The results showed that the contamination of PBDEs in the leaf samples had good correlation with the soil around them.


Catalytic contributions of key residues in the adenine glycosylase MutY revealed by pH-dependent kinetics and cellular repair assays.
MutY prevent DNA mutations associated with 8-oxoguanine (OG) by catalyzing the removal of adenines opposite OG. pH dependence of the adenine glycosylase activity establish that Asp 138 of MutY must be deprotonated for maximal activity consistent with its role in stabilizing the oxacarbenium ion transition state in an S(N)1 mechanism. A cellular OG:A repair assay allowed further validation of the critical role of Asp 138. Conservative substitutions of the catalytic residues Asp 138 and Glu 37 resulted in enzymes with a range of activity that were used to correlate the efficiency of adenine excision with overall OG:A repair and suppression of DNA mutations in vivo. The results show that MutY variations that exhibit reduced mismatch affinity result in more dramatic reductions in cellular OG:A repair than those that only compromise adenine excision catalysis.


Paraquat poisoning is not necessarily fatal.
This paper describes a case of deliberate ingestion of paraquat successfully managed with gastric lavage, forced diuresis, haemodialysis, gastrointestinal purgation and the adminstration of specific adsorbents.


Relative efficacy and safety of Janus kinase inhibitors for the treatment of active psoriatic arthritis: a network meta-analysis.
To determine the relative effectiveness and safety of Janus kinase (JAK) inhibitors in active psoriatic arthritis (PsA) patients. A Bayesian network meta-analysis was performed using data from randomized controlled trials (RCTs) to evaluate the effectiveness and safety of upadacitinib 30 mg, upadacitinib 15 mg, tofacitinib 10 mg, tofacitinib 5 mg, and filgotinib 200 mg in active PsA patients. Five RCTs including 2539 patients fulfilled the inclusion criteria. The surface under the cumulative ranking curve (SUCRA) revealed that filgotinib 200 mg had the highest probability of reaching a 20% American College of Rheumatology (ACR20) response rate, followed by upadacitinib 30 mg, upadacitinib 15 mg, tofacitinib 10 mg, tofacitinib 5 mg, and placebo. Upadacitinib 30 mg had the highest probability of achieving the ACR50 and ACR70 response rates, followed by upadacitinib 15 mg, filgotinib 200 mg, tofacitinib 10 mg, tofacitinib 5 mg, and placebo. The SUCRA rating based on the Psoriasis Area and Severity Index response rate of at least 75% (PASI75) showed that tofacitinib 10 mg had the highest probability of achieving this response, followed by upadacitinib 15 mg, filgotinib 200 mg, tofacitinib 5 mg, and placebo. Safety analyses evaluated adverse events (AEs) and serious adverse events (SAEs), but no statistically relevant differences were found. Based on the ACR response rates, filgotinib 200 mg and upadacitinib 30 mg were the most effective, whereas tofacitinib 10 mg was the most effective treatment for PsA based on PASI75. However, treatment options were similar with regard to AEs and SAEs.


Determinants of patients' delay with disability in the diagnosed leprosy cases in the three major states of India: A case-control study.
Skin lesions are the most common early symptoms of leprosy, often ignored by patients at an early stage and misdiagnosed as other dermatological diseases by healthcare personnel, leading to delay in diagnosis and treatment of leprosy precipitating permanent neurological deficit, deformities and serious disabilities. The objective is to evaluate the duration of delay and factors responsible for the delay in reporting of patients, among the newly detected leprosy cases (Grade 1 and Grade 2 disability patients). A case-control study was conducted during 2014-2016 in three major states of India (Delhi, Gujarat and West Bengal) in 140 randomly recruited newly registered adult leprosy patients (aged 18 years and above) with Grade 2/1 disabilities (cases) and 140 Grade 0 disability patients (controls) in each of these Indian states. It is established that the major contributors for the delay in the early diagnosis of leprosy have been patient-related factors. The median patient delay in the three states of Delhi, Gujarat and West Bengal were five months (0.7-1.8), 2.8 months (2-14) and 12 months (2-24), respectively. The study design is case-control and has an inbuilt reporting bias due to the retrospective nature of data collection but the data collection was carried with caution to reduce the recall bias. As the study is carried out in three states, generalisation of interpretation was cautiously executed. The matching ratio of cases and controls was 1:1 in this study, but we could not increase the controls due to operational feasibility during the conduct of the study. Patient delay is a crucial factor responsible for the disability among new leprosy cases. A higher patient delay in these three states reflects that the community is not aware about the signs and symptoms of leprosy. Reducing patient delay is very important for reducing disabilities in the newly diagnosed cases.


Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies.
Genomic profiling revealed the identity of at least 5 subtypes of diffuse large B-cell lymphoma (DLBCL), including the MCD/C5 cluster characterized by aberrations in MYD88, BCL2, PRDM1, and/or SPIB. We generated mouse models harboring B cell-specific Prdm1 or Spib aberrations on the background of oncogenic Myd88 and Bcl2 lesions. We deployed whole-exome sequencing, transcriptome, flow-cytometry, and mass cytometry analyses to demonstrate that Prdm1- or Spib-altered lymphomas display molecular features consistent with prememory B cells and light-zone B cells, whereas lymphomas lacking these alterations were enriched for late light-zone and plasmablast-associated gene sets. Consistent with the phenotypic evidence for increased B cell receptor signaling activity in Prdm1-altered lymphomas, we demonstrate that combined BTK/BCL2 inhibition displays therapeutic activity in mice and in five of six relapsed/refractory DLBCL patients. Moreover, Prdm1-altered lymphomas were immunogenic upon transplantation into immuno-competent hosts, displayed an actionable PD-L1 surface expression, and were sensitive to antimurine-CD19-CAR-T cell therapy, in vivo. Relapsed/refractory DLBCL remains a major medical challenge, and most of these patients succumb to their disease. Here, we generated mouse models, faithfully recapitulating the biology of MYD88-driven human DLBCL. These models revealed robust preclinical activity of combined BTK/BCL2 inhibition. We confirmed activity of this regimen in pretreated non-GCB-DLBCL patients. See related commentary by Leveille et al., p. 8. This article is highlighted in the In This Issue feature, p. 1.


Transition of Care of Pediatric Patients with Special Needs to Adult Care Settings: Children with Diabetes Mellitus and Other Endocrine Disorders.
Childhood onset endocrine disorders need long-term medical, psychological and social management. Over time, many illnesses evolve, while others may witness onset of new complications. Thus, the components of the care change as the child grows into adolescence and then adulthood. The transition of children and adolescents with chronic endocrine disorders to adult care continues to be a major challenge. Pediatric and adult healthcare teams should together design a transitional care plan that is developmentally appropriate and responsive to the needs of young adults. The preparation for transition to adult care should begin early in adolescence and involve both the adolescent and his parents. A structured and planned transitional care bridges the gap between pediatric and adult care teams, promote ongoing engagement and build trust with the new healthcare teams. Combined pediatric-adult care transition model for endocrine conditions has yielded high adherence rates and patient satisfaction.


Ultrastructure of Hemolivia mariae gamonts in the blood of the lizard Tiliqua rugosa and their development to oocyst stage in the tick Amblyomma limbatum.
The ultrastructural features of the development of Hemolivia mariae from intra-erythrocytic gamonts in their host, the Australian lizard Tiliqua rugosa, to oocysts containing sporokinetes in their vector, the tick Amblyomma limbatum, are described. Mature intra-erythrocytic gamonts, as well as gamonts ingested by the tick were encased in a thick (30 nm) capsule with distinct suture sites at each of the two apices. In the only image of a presumed syzygy, both partners were still encased. Further stages, the young and ongrowing oocysts, were bound by a membranous wall. Sporokinetes developed within the oocyst around a primordial crystalloid body. The fully differentiated sporokinetes, still resting within the oocyst wall, exhibited a very short conoid in the apical complex and were heavily loaded with crystalloid material.


Lung epithelial H292 cells induce differentiation of immature human HMC-1 mast cells by interleukin-6 and stem cell factor.
Immature mast cells migrate into tissues where they differentiate into mature mast cells under the influence of local factors. In the airways of asthmatics increased numbers of chronically activated mast cells are located nearby the airway epithelium. The aim of this study was to evaluate whether and, if so, which products released by epithelial cells may affect mast cell proliferation and differentiation. We performed in vitro studies using the human lung mucoepidermoid carcinoma-derived H292 cell line and the immature human mast cell line, HMC-1. Proliferation was assessed by 3H-thymidine incorporation. Differentiation of HMC-1 cells was inferred from tryptase production. Exposure of HMC-1 cells to medium conditioned for 48 h by H292 cells resulted in a reduction of proliferation with 65 +/- 4.9% (mean +/- SEM, n = 9) at day 5. Culturing HMC-1 cells for 8 days in the presence of H292-conditioned medium resulted in morphological changes indicative of differentiation, and in a 3.0 +/- 0.4-fold increase of tryptase production (P = 0.0039, n = 9). Conditioned medium from H292 cells that were stimulated by LPS also inhibited HMC-1 proliferation. Inhibitory antibodies against two mediators from H292 cells, interleukin-6 (IL-6) and stem cell factor (SCF), abolished the increase in HMC-1 tryptase production induced by H292-conditioned medium. Recombinant human (rh) IL-6, but not rhSCF, reduced HMC-1 proliferation with 44% and 13% at day 3 and 5, respectively. Surprisingly, rhIL-6 did not increase HMC-1 tryptase production significantly whereas incubation with rhSCF did (1.5 +/- 0.1-fold, P = 0.002, n = 10) although the increase was less than observed for conditioned medium. Epithelial-derived IL-6 and SCF are implicated in differentiation of HMC-1 cells but additional factors are not excluded. As activated primary bronchial epithelial cells also express IL-6 and SCF, it should be considered that these cells are involved in mast cell differentiation within the airways, particularly in diseases where epithelial cells are activated, such as asthma.


On the mechanism of prometaphase congression: chromosome velocity as a function of position on the spindle.
Rates of movement of univalents at prometaphase and of half-bivalents at anaphase in living cricket and grasshopper spermatocytes were determined as a function of the distance from the pole toward which the movement was directed. In the artificially produced univalents of cricket cells, correlation coefficients for rate versus distance form the pole were widely disparate from movement to movement and there was no consistent relationship between velocity and distance from the pole. However, in the naturally occurring univalents of grasshopper cells, there was a significant positive correlation between velocity and distance from the pole. In both cricket and grasshopper cells, there was no consistent correlation between rate of movement and distance from the pole for half-bivalents at anaphase. The prometaphase data from grasshopper cells support the simple hypothesis of Ostergren (1950) that congression results from the application to chromosomes of forces which increase with increasing distance from the pole. Furthermore, these data are consistent with models of force production which suppose that the relationship between force (reflected as velocity) and distance from the pole is a linear one.


Blood volume in newborn piglets: effects of time of natural cord rupture, intra-uterine growth retardation, asphyxia, and prostaglandin-induced prematurity.
Blood volume (BV), red cell mass (RCM; Cr-51) and plasma volume (125I-labeled albumin) were measured in 205 piglets from 28 litters shortly after birth. Spontaneous cord rupture in healthy piglets occurred during delivery (n = 25) or within 190 sec of birth (n = 82). Spontaneous and induced delay of cord rupture resulted in a time-dependent increase in BV and RCM. BV (x +/- S.D.) at birth was 72.5 +/- 10.5 ml/kg (RCM, 23.6 +/- 4.6 ml/kg) in the 25 piglets with prenatal cord rupture and 110.5 +/- 12.9 ml/kg (RCM, 38.4 +/- 7.0 ml/kg) in 17 piglets with late spontaneous cord rupture. The mean blood volume of all the 107 healthy piglets with spontaneous cord rupture was 90.2 +/- 12.7 ml/kg (RCM, 30.1 +/- 4.8 ml/kg). RCM was significantly (P less than 0.05) increased in nine piglets with intra-uterine growth retardation (RCM, 35.8 +/- 11.2 ml/kg) and in 13 with metabolic acidosis but without signs of asphyxia (RCM, 35.8 +/- 6.7 ml/kg). In five piglets with cord wrapping, prenatal cord rupture, and acute asphyxia, BV (57.8 +/- 7.3 ml/kg) was significantly decreased. In five other piglets with prenatal cord rupture and acute asphyxia, BV (67.9 +/- 10.0 ml/kg) corresponded to that of the normal piglets with prenatal cord rupture. However, delay of cord rupture to 60 sec after birth did not increase BV (66.0 +/- 11.8 ml/kg) in four piglets with acute asphyxia. Forty-one premature piglets delivered 6 days before normal term had their cords ruptured prenatally or within 5 sec of birth. Their hematocrit at birth (0.337 +/- 0.028 liters/liter) was significantly decreased compared to the normal full-term piglets with corresponding time of cord rupture (0.384 +/- 0.033 liters/liter). RCM in 18 piglets with prostaglandin-induced prematurity (18.9 +/- 3.4 ml/kg) was significantly lower than in 23 piglets whose births had been induced by ovarectomy of their mother (RCM, 22.1 +/- 3.2 ml/kg).


Importance of enantiomeric purity and its control by thin-layer chromatography.
Methods for the direct resolution of enantiomers are important and are necessary for pharmaceutical and biomedical analysis, synthetic and mechanistic studies and various other fields. The present paper deals with the results of recent approaches, such as ligand exchange, ion exchange and steric interactions, providing direct resolution of enantiomers of a variety of compounds by thin-layer chromatography. General aspects of various methods for analysis of enantiomeric purity and resolution have been compared.


Incidence and adverse clinical events of primary sclerosing cholangitis with ulcerative colitis.
The aim of this study was to conduct a nationwide population-based study to estimate the incidence of primary sclerosing cholangitis in patients with ulcerative colitis (UC-PSC) and investigate healthcare use, medication use, surgery, cancer, and death as adverse clinical events of UC-PSC. We identified incident cases of UC with (UC-PSC) or without PSC (UC-alone) between 2008 and 2018 using health insurance claims data in Korea. Univariate (crude hazard ratio (HR)) and multivariate analyses were performed to compare the risk of adverse clinical events between groups. A total of 14,406 patients with UC using population-based claims data were detected in the cohort. Overall, 3.38% (487/14,406) of patients developed UC-PSC. During a mean follow-up duration of approximately 5.92 years, the incidence of PSC in patients with UC was 185 per 100,000 person-years. The UC-PSC group showed statistically more frequent healthcare use (hospitalization and emergency department visits: HRs, 5.986 and 9.302, respectively; P < .001), higher immunomodulator and biologic use (azathioprine, infliximab, and adalimumab: HRs, 2.061, 3.457, and 3.170, respectively; P < .001), and higher surgery rate (operation for intestinal obstruction, and colectomy: HRs, 9.728 and 2.940, respectively; P < .001) than did the UC-alone group. The UC-PSC group also showed significantly higher colorectal cancer and biliary tract cancer (HRs, 2.799 and 36.343, respectively; P < .001) and mortality (HR, 4.257) rates than did the UC-alone group. Patients with UC-PSC have higher risks of colorectal cancer, biliary tract cancer, and death than do patients with UC-alone. Although considered a rare disease, managing this complex and costly disease requires recognition of the impact of increased burden on healthcare services.


Dimensions of religiousness and spirituality as predictors of well-being in advanced chronic heart failure patients.
We examined relationships between seven dimensions of religion/spirituality (RS) (forgiveness, daily spiritual experiences, belief in afterlife, religious identity, religious support, public practices, and positive RS coping) and three dimensions of well-being (physical, mental, and existential) in a sample of 111 patients with advanced chronic heart failure. Participants completed questionnaires at baseline and 3 months later. Results showed that fairly high levels of RS were reported on all seven dimensions. Furthermore, RS dimensions were differentially related to well-being. No aspect of RS was related to physical well-being, and only a few aspects were related to mental well-being. Forgiveness was related to less subsequent depression, while belief in afterlife was related to poorer mental health. All aspects of RS were related to at least one aspect of existential well-being. In particularly, daily spiritual experiences were linked with higher existential well-being and predicted less subsequent spiritual strain. These results are consistent with the view that in advanced disease, RS may not affect physical well-being but may have potent influences on other aspects of well-being, particularly existential aspects.


Diagnosis of urethritis: role of polymorphonuclear leukocyte counts in gram-stained urethral smears.
Polymorphonuclear leukocytes (PMNs) in the gram-stained urethral smears of 236 consecutive sexually active men without gonorrhea were analyzed quantitatively. The frequency distribution of the highest count of PMNs per high-power field (hpf) showed a count of four PMNs to be the "cut-off" point separating men with urethritis from those without urethritis. This cut-off point correlated well with the presence of Chlamydia trachomatis as well as with turbid urine. However, the PMN count in the gram-stained urethral smear was found to be more sensitive than the appearance of the urine in the diagnosis of urethritis among those with minimal symptoms and signs and not harboring C. trachomatis. This study also demonstrated a close similarity as regards clinical features and PMN count in gram-stained urethral smears between those harboring Ureaplasma urealyticum and those with no organisms.


Over-expression of the cell death regulator BAX inhibitor-1 in barley confers reduced or enhanced susceptibility to distinct fungal pathogens.
BAX inhibitor-1 (BI-1) is a conserved cell death regulator protein that inhibits mammalian BAX-induced cell death in yeast, animals and plants. Additionally, HvBI-1 suppresses defense responses and resistance to the powdery mildew fungus Blumeria graminis f.sp. hordei (Bgh) when over-expressed in single epidermal cells of barley. To test the potential of ectopic expression of BI-1 to influence fungal interactions with crop plants, we produced stable transgenic barley plants expressing a green fluorescing protein (GFP) fusion of HvBI-1 under control of the cauliflower mosaic virus 35S promoter. GFP-HvBI-1 plants were fertile and did not display obvious developmental alterations when compared to wild type parents. GFP-HvBI-1 plants were more resistant to single cell death induced by ballistic delivery of a mammalian proapototic BAX expression construct and more susceptible to biotrophic Bgh. Microscopic observation of the interaction phenotype revealed that enhanced susceptibility, i.e. a higher degree of successful establishment of haustoria in epidermal cells, was associated with a reduced frequency of hypersensitive cell death reactions. In contrast, young seedlings of GFP-HvBI-1 barley were more resistant to Fusarium graminearum than wild type or azygous controls. Hence the effect of GFP-HvBI-1 on the outcome of a particular plant-fungus interaction appeared dependent on the lifestyle of the pathogen.


Nanotechnology Driven Approaches for the Management of Parkinson's Disease: Current Status and Future Perspectives.
Parkinson's disease (PD) is believed to be one of the commonly found adult-onset movement disorder occurring due to neurodegeneration and striatal dopamine deficiency. Although clinical diagnosis depends on the occurrence of bradykinesia and other cardinal motor features, PD is linked with many non-motor symptoms that are responsible for overall disability. Among several factors, genetic and environment-related factors are thought to be the major ones accountable for PD. Comprehensive research has shown that a number of drugs are effective in providing symptomatic relief to the patients suffering from PD. But some drug molecules suffer from significant drawbacks such as poor bioavailability and instability, therefore, they sometimes fail to deliver the expected results. Hence, to resolve these issues, new promising novel drug delivery systems have been developed. Liposomes, solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery system (SEDDS), niosomes are some of the novel drug delivery system (NDDS) carriers that have been explored for enhancing the CNS concentration of levodopa, apomorphine, resveratrol, and other numerous drugs. This paper elucidates various drugs that have been studied for their potential contribution to the treatment and management of PD and also reviews and acknowledges the efforts of several scientists who successfully established various NDDS approaches for these drugs for the management of PD.


Mapping the Oncological Basis Dataset to the Standardized Vocabularies of a Common Data Model: A Feasibility Study.
In their joint effort against cancer, all involved parties within the German healthcare system are obligated to report diagnostics, treatments, progression, and follow-up information for tumor patients to the respective cancer registries. Given the federal structure of Germany, the oncological basis dataset (oBDS) operates as the legally required national standard for oncological reporting. Unfortunately, the usage of various documentation software solutions leads to semantic and technical heterogeneity of the data, complicating the establishment of research networks and collective data analysis. Within this feasibility study, we evaluated the transferability of all oBDS characteristics to the standardized vocabularies, a metadata repository of the observational medical outcomes partnership (OMOP) common data model (CDM). A total of 17,844 oBDS expressions were mapped automatically or manually to standardized concepts of the OMOP CDM. In a second step, we converted real patient data retrieved from the Hamburg Cancer Registry to the new terminologies. Given our pipeline, we transformed 1773.373 cancer-related data elements to the OMOP CDM. The mapping of the oBDS to the standardized vocabularies of the OMOP CDM promotes the semantic interoperability of oncological data in Germany. Moreover, it allows the participation in network studies of the observational health data sciences and informatics under the usage of federated analysis beyond the level of individual countries.


Experimental study and theoretical prediction of mechanical properties of ultra-high-performance concrete incorporated with nanorice husk ash burning at different temperature treatments.
This research aimed to investigate the effect of nanorice husk ash (NRHA) prepared using different thermal treatment methods on ultra-high-performance concrete (UHPC) behaviour. NRHA was prepared by two methods: (1) burning for 3 h at 300, 500, 700 and 900 °C and (2) burning for different durations (9, 7, 5 and 3 h) at 300, 500, 700 and 900 °C. NRHA was added to UHPC to make 25 mixtures with three dosages (1%, 3% and 5%). Density, compressive strength, tensile strength, flexure strength and ultrasonic pulse velocity tests were performed at the experimental level. Moreover, full microstructure analysis, including X-ray diffractometry, Brunauer-Emmett-Teller surface area analysis, thermogravimetric analysis, scanning electron microscopy and energy-dispersive X-ray spectroscopy, was performed. The best performances in in the first method (constant duration, different temperatures) were obtained by 1% NRHA burned at 900 °C with 12.5% compressive strength and 1% NRHA burned at 700 °C with increased ratio (10%). Moreover, the best performance in the second method (different burning durations and temperatures) was obtained by 3% NRHA with a ratio of 22.5% at 700 °C for 5 h. Burning rice husk ash improved the compressive strength. It also remarkably improved the splitting tensile strength and flexure strength by 32% and 47%, respectively, at 3% NRHA treated at 700 °C for 3 h. The microstructural analysis showed the efficient role of NRHA in the compactness of concrete sections. It improved the formation of new calcium silicate hydrate gel; decreased the cracks, voids, CaCO3 and Ca(OH)2; and increased the Ca/Si composition. The obtained experimental results were used to build an artificial neural network (ANN) to predict UHPC properties. The ANN model was used as a validation tool to determine the correlation between results. Results showed a remarkable improvement in the mechanical properties of UHPC incorporating NRHA for all mixtures. The ANN model indicated a reliable correlation between input and output variables. The R2 values for the training, validation and testing steps were all 0.99.


Watch this! Observed tool use affects perceived distance.
Recent research has shown that being able to interact with an object causes it to be perceived as being closer than objects that cannot be interacted with. In the present study, we examined whether that compression of perceived space would be experienced by people who simply observed such interactions by others with no intention of performing the action themselves. Participants judged the distance to targets after observing an actor reach to an otherwise unreachable target with a tool (Experiment 1) or illuminate a distant target with a laser pointer (Experiment 2). Observing either type of interaction caused a compression of perceived space, revealing that a person's perception of space can be altered through mere observation. These results indicate that shared representations between an actor and observer are engaged at the perceptual level easily and perhaps automatically, even in the absence of cooperation or an observer's own intention to interact.


Psychological-health correlates of physical activity and sedentary behaviour during the COVID pandemic.
While physical inactivity is associated with adverse psychological outcomes, less is known about the psychological outcomes associated with sedentary behaviour, and specifically, its mentally active and passive forms. The COVID-19 pandemic represents a unique opportunity to study associations between these variables in light of widespread stay-at-home mandates and restrictions on outdoor exercise/social activities. Using a cross-sectional dataset acquired during the COVID-19 pandemic in Australia, we examined whether physical activity and sedentary behaviour were associated with subjective quality of life (sQoL) and subjective cognitive dysfunction, and whether these associations were mediated by depressive symptoms. 658 participants (males = 169, females = 489) self-reported data on physical activity and sedentary behaviour in an online survey during May 2020-May 2021. Data on physical activity and sedentary behaviour (both mentally active and passive types) was compared according to whether it was collected during or out of a lockdown period. Regression models were used to test associations of physical activity and sedentary behaviour with sQoL and subjective cognitive dysfunction, and whether these associations were mediated by depression severity. Physical activity was beneficially associated with sQoL, whereas sedentary behaviour (both total hours and the reduction of mentally active/increase in mentally passive behaviour) was detrimentally associated with sQoL. These associations were mediated by depression severity. Physical activity and sedentary behaviour were also indirectly associated with subjective cognitive dysfunction by virtue of their associations with depression severity. There are important differences in the psychological correlates of mentally passive and active sedentary behaviours. Our findings suggest that health promotion strategies should focus on not only increasing physical activity but also reducing passive sedentary behaviours as a means of maintaining good psychological health.


Ascending aorta-right pulmonary artery anastomosis. Long-term results in 137 patients with cyanotic congenital heart disease.
Long-term follow-up of 137 patients who had an ascending aorta-right pulmonary artery anastomosis at the Children's Hospital of Philadelphia between 1966 and 1975 is presented. One hundred four patients survived the first hospitalization. Of the 81 patients currently alive, 30 have had a succesful corrective. operation. Nine patients died at the time of correction. Fifty patients have adequate pallation. Of the 56 deaths, only nine were shunt related. Late complications in the 104 first admission survivors included congestive heart failure (23%), pulmonary artery hypertension (7%), pulmonary vascular obstructive disease (1%), and shunt failure (9%). Special catheterization techniques to evaluate the shunt and its effect on the pulmonary arteries prior to surgical correction are described. The ascending aorta-right pulmonary artery anastomosis can provide effective palliation without interfering with subsequent corrective operations.


Determinants of renal volume in autosomal-dominant polycystic kidney disease.
The Consortium of Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) recently showed that renal enlargement in autosomal-dominant polycystic kidney disease mimicked exponential growth. We determined the effects of cyst initiation rate, total number, and growth rate on the time-dependent change of total cyst volume (TCV). Mathematical models with equations integrating cyst surface area, volume, and an invariant growth rate constant were used to compute the time-dependent change in volume of solitary and multiple cysts. Multiple expanding cysts increased TCV in an exponential-like pattern even when individual cysts formed at different rates or exhibited different but constant growth rates. TCV depended on the rate of cyst initiation and on the total number of cysts; however, the compounding effect of exponential-like growth was the most powerful determinant of long-term cyst expansion. Extrapolation of TCV data plots for individual subjects back to an age of 18 predicted TCV values within an established range. We conclude that cysts started early in life were the main contributor to eventual TCV while their growth rate primarily determined renal size; although the rate of formation and the ultimate number of cysts also contributed. The good fit between the exponential models and the extrapolated CRISP data indicates that the TCV growth rate is a defining trait for individual patients and may be used as a prognostic marker.


A Novel Method of Implant Coverage for Post-Mastectomy Reconstruction after Previous Augmentation: A Case Report.
Breast augmentation is the most common -cosmetic surgical procedure in the USA, with nearly 300,000 women undergoing surgery annually. National incidence rates predict that among women undergoing breast augmentation each year, approximately 35,000 will eventually be diagnosed with breast cancer, in particular individual BRCA1/2 germline mutant carriers. Our case introduces a novel method of implant coverage after immediate post-mastectomy reconstruction in augmented patients. A novel "capsular flap" (flap of the pre-existing old capsule) is isolated and refolded to cover the outer lower portion of the implant. Tailored surgical approaches can be offered to those patients previously augmented and requiring mastectomy after breast cancer diagnosis.


Evidence that MEHP inhibits rat granulosa cell function by a protein kinase C-independent mechanism.
We have recently shown that mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the reproductive toxicant di-(ethylhexyl) phthalate (DEHP), inhibited FSH- but not forskolin-, isoproterenol-, or cholera toxin-stimulated granulosa cell cAMP accumulation in vitro. In addition, MEHP also inhibited FSH-stimulated progesterone production, a cAMP-dependent process. Similar to MEHP, the protein kinase C (PKC) activator, 12-0-tetradecanoyl-phorbol 13-acetate (TPA) has been shown to inhibit rat granulosa cell cAMP accumulation in a FSH-specific manner, and decrease FSH-stimulated progesterone production. Due to the similarity with respect to inhibition of cAMP accumulation, we conducted studies to determine if the inhibitory actions of MEHP on granulosa cell function are mediated via activation of PKC. Treatment of granulosa cells for 48 h with 100 microM MEHP produced no effect on forskolin- or isoproterenol-stimulated progesterone production, indicating that MEHP does not have a post-cyclic AMP site of action with respect to progesterone inhibition. Unlike the FSH-specific effect seen with MEHP, treatment with 10 nM TPA inhibited FSH-, forskolin-, and isoproterenol-stimulated progesterone production. In addition, maximally inhibitory concentrations of TPA and MEHP caused significantly greater inhibition of FSH-stimulated cAMP accumulation than either compound alone. Finally, addition of the progesterone precursor, pregnenolone, reversed the FSH-stimulated progesterone production inhibition by MEHP, but not that by TPA. Taken together, these data indicate that the inhibitory effects of MEHP on granulosa cell function are independent of phorbol ester-sensitive PKC activation.


Familial Creutzfeldt-Jakob disease in Japan. Three cases in a family with white matter involvement.
Three cases of Creutzfeldt-Jakob disease occurring in one family have been clinicopathologically examined. Although the age at onset, duration, and age at death differed for each case, pathological findings, including diffuse neuronal loss, astrocytosis, spongiform changes and patchy and/or diffuse white matter involvement were similar. Life histories and inheritance patterns of the present 3 cases and 2 other families previously reported in Japan are compared with the general findings for familial cases in western countries.


Effect of thiols enrichment on Cr(VI) photo-reduction by natural organic matter (NOM).
Photochemical redox transformation of Cr(VI)-NOM complexes substantially affects transport and speciation of less toxic Cr(III) in natural waters. However, the underlying mechanisms remain unclear. This study reported photochemical reactions of Cr(VI) with thiol-enriched NOM under acidic condition. More effective thiols enrichment in humic acid (HA) was observed than that in fulvic acid (FA), thereby resulting in a higher reduction capacity and faster rate of Cr(VI) photo-reduction. Chemical addition of sulfide to HA formed a large number of S-containing molecular formulae, which subsequently disappeared following reactions with Cr(VI) under solar irradiation. Cr(VI) photo-reduction in thiol-enriched HA consumed more S-containing formulae. Solar irradiation caused a rapid loss of the reduction capacities and thiol contents in HA and FA. All these findings can provide useful information for understanding the biogeochemical cycles of chromium and sulfur, and are also of environmental significance because they may partially account for photo-transformation of Cr(VI) when chromium enters into the aquatic environment as acidic industrial effluents.


"Jing-Ning Granules" Can Alleviate Attention Deficit Hyperactivity Disorder in Rats by Modulating Dopaminergic D2/D1-Like Receptor-Mediated Signaling Pathways.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention deficit, hyperactivity, and impulsivity. Jing-Ning Granules (JNG) is a traditional Chinese medicine (TCM) that can alleviate ADHD. Although JNG is commonly used for the effective treatment of ADHD and has obtained the national invention patent, the exact mechanism of action remains unclear. In this study, we examined the effect and mechanism of JNG in spontaneously hypertensive rats (SHRs). We hypothesized that JNG affects dopaminergic D2/D1-like receptors and related pathways. Six rat groups were used in the experiment: Wistar-Kyoto rats (WKY, control group) and five SHR groups, including a model group; atomoxetine (ATX, positive control) group; and low, medium, and high-dose JNG groups. The corresponding treatments were daily administered to each group for 6 weeks. A behavioral test, including a step-down test and open field test (OFT), was carried out at the end of treatment. After the behavioral test, all animals were sacrificed, and the brain tissue was collected and analyzed ex vivo; histopathological analysis was performed to assess the pathological changes of the hippocampus; expression of D1-like and D2-like receptors, sensor protein calmodulin (CaM), protein kinase A (PKA), and calcium/calmodulin-dependent serine/threonine protein kinase (CaMKII) in the striatum and hippocampus was measured by western blot and real-time quantitative PCR (RT-PCR); cyclic adenosine monophosphate (cAMP) levels in the striatum were analyzed using an enzyme-linked immunosorbent assay (ELISA), while the level of Ca2+ in the striatum was analyzed by a calcium kit. Our results showed that ATX or JNG could ameliorate the hyperactive/impulsive behavior and cognitive function of ADHD by promoting neuroprotection. Mechanistically, ATX or JNG could prompt the expressions of Dl-like and D2-like receptors and improve the mRNA and protein levels of cAMP/PKA and Ca2+/CAM/CAMKII signaling pathways. These results indicate that JNG can produce therapeutic effects by regulating the balance of D2/D1-like receptor-mediated cAMP/PKA and Ca2+/CaM/CaMKII signaling pathways.


Current issues in the surgical management of breast cancer: a review of abstracts from the 2002 San Antonio Breast Cancer Symposium, the 2003 Society of Surgical Oncology annual meeting, and the 2003 American Society of Clinical Oncology meeting.
Three areas of development in the surgical management of breast cancer received significant attention in 2003--breast-conserving surgery, sentinel lymph node (SLN) biopsy, and ductal lavage. Provocative investigations focusing on these controversial aspects of surgical care were presented at major national oncology meetings throughout the year. The recently published 20-year updates by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the Italian National Cancer Institute confirm the survival equivalence of breast-conserving surgery and mastectomy in early stage disease. Data reveal, however, that this strategy is underutilized in the United States when compared with other countries. A meta-analysis of close to 70 published trials on the use of SLN biopsy has revealed an overall SLN identification rate of greater than 90%, with a false-negative rate of 8.4%. Two major controversies remain to be resolved: Is there a subset of sentinel node-positive patients who may safely avoid complete axillary lymph node dissection? What is the best way integrate lymphatic mapping into neoadjuvant chemotherapy protocols? The strength of ductal lavage as a risk assessment adjunct is related to the ability to detect cellular atypia, a feature associated with a three- to fivefold increased risk for breast cancer. This technique continues to be rigorously evaluated in a number of ongoing studies.


Sudden death in the chronic alcoholic.
A review of the causes of sudden death in 500 chronic alcoholics is presented. The deaths were fairly equally distributed between trauma, natural causes, acute intoxication and alcohol related disease. In a small but significant number, the cause is not initially clear although distinct patterns of death were evident.


Inbreeding Alters the Gut Microbiota of the Banna Minipig.
The gut microbiota coevolve with the host and can be stably transmitted to the offspring. Host genetics plays a crucial role in the composition and abundance of gut microbiota. Inbreeding can cause a decrease of the host's genetic diversity and the heterozygosity. In this study, we used 16S rRNA gene sequencing to compare the differences of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to understand the impact of inbreeding on the gut microbiota. Three dominant bacteria (Stenotrophlomonas, Streptococcus, and Lactobacillus) were steadily enriched in both the Diannan small-ear pig and Banna minipig inbred. After inbreeding, the gut microbiota alpha diversity and some potential probiotics (Bifidobacterium, Tricibacter, Ruminocaccae, Christensenellaceae, etc.) were significantly decreased, while the pathogenic Klebsiella bacteria was significantly increased. In addition, the predicted metagenomic analysis (PICRUSt2) indicated that several amino acid metabolisms (''Valine, leucine, and isoleucine metabolism'', ''Phenylalanine, tyrosine, and tryptophan biosynthesis'', ''Histidine metabolism'') were also markedly decreased after the inbreeding. Altogether our data reveal that host inbreeding altered the composition and the predicted function of the gut microbiome, which provides some data for the gut microbiota during inbreeding.


Effect of chlorpromazine on drug absorption and gastric emptying in man.
In a double-blind study the effect of a single IV dose (25 mg) of chlorpromazine on gastric emptying, as determined by the rate of paracetamol absorption, was measured in seven healthy volunteers. Each volunteer acted as his/her own control. There was no significant difference between the maximum paracetamol concentration, the time to reach the plasma maximum concentration, and the area under the plasma concentration time curve from 0-120 minutes on the two occasions, indicating unchanged gastric emptying after administration of chlorpromazine.


Posterior spinal fusion to sacrum in non-ambulatory hypotonic neuromuscular patients: sacral rod/bone graft onlay method.
A retrospective study involving 65 non-ambulatory patients with hypotonic neuromuscular scoliosis has assessed the effectiveness of a sacral rod/bone onlay technique for extending spinal fusion to the sacrum. To extend posterior spinal fusion to the sacrum, we used either 1 Harrington rod and 1 Luque L rod with sublaminar wires in 14 patients (Group 1) or two rods with sublaminar wires in 51 patients (Group 2) along with abundant autograft and allograft bone covering the ends of the rods. Diagnoses were Duchenne muscular dystrophy 53, spinal muscular atrophy 4, myopathy 3, limb girdle muscular dystrophy 2, infantile FSH muscular dystrophy 1, cerebral palsy 1, and Friedreich ataxia 1. Mean age at surgery was 14.3 years (±2.2, range 10.9-25.2). Radiographic follow-up (2 years post-surgery or greater) was 6.4 years (±4.4, range 2-25.3). Using the onlay technique, all patients fused with no rod breakage or pseudarthrosis. For the entire series, the mean pre-operative scoliosis was 54.7° (±31.1, range 0°-120°) with post-operative correction to 21.8° (±21.7, range 0°-91°) and long-term follow-up 24° (±22.9, range 0°-94°). For pelvic obliquity, pre-operative deformity was 17.3° (±11.3, range 0°-51°) with post-operative correction to 8.9° (±7.8, range 0°-35°) and long-term follow-up 10.1° (±8.1, range 0°-27°). Five required revision at a mean of 3.3 years post-original surgery involving rod shortening at the distal end. One of these had associated infection. Lumbosacral stability and long-term sitting comfort have been achieved in all patients. Problems can be minimized by positioning the rods firmly against the sacrum at the time of surgery with a relatively short extension beyond the L5-S1 junction. The procedure is valuable in hypotonic non-ambulatory neuromuscular patients whose immobility enhances the success rate for fusion due to diminished stress at the lumbosacral junction. It is particularly warranted for those with osteoporosis and a small, deformed pelvis. Considerable weight loss and lengthy rods not closely apposed to the sacrum at the time of surgery played a major role in patients needing revision.


Pregnancy hypertension, placental evidences of low uteroplacental blood flow, and spontaneous premature delivery.
This study was undertaken to determine if preeclampsia and low uteroplacental blood flow cause spontaneous preterm births. No non-invasive methods are currently available to accurately measure uteroplacental blood flow, so surrogates that are known to be associated with low uteroplacental flow were used. These are preeclampsia, placental infarcts, abnormally small placental villi, and excessive syncytial knots. Preeclampsia was associated with a frequency of spontaneous preterm births that was 41% greater than expected (P less than .001). Normotensive gestations with placental findings of low uteroplacental blood flow ended preterm 147% more frequently than expected, and when a woman had two such pregnancies in succession, the second had a particularly high frequency of spontaneous preterm delivery (64%). Overall, preeclampsia and placental findings of low uteroplacental blood flow were associated with 26% of the spontaneous preterm deliveries in this study. Preeclampsia and low uteroplacental blood flow may be major causes of preterm birth.


Review, monitor, educate: A quality improvement initiative for sustained chest radiation reduction in pediatric trauma patients.
We hypothesize that in pediatric trauma patients, CT scans after normal chest x-rays do not add information that alters clinical decision making. A retrospective review of trauma patients < 15 years with chest imaging evaluated at a pediatric trauma center between 1/2013 and 6/2019 was performed. Imaging was reviewed for significant findings that could affect care. A guideline was established in January 2017 which emphasized x-rays prior to CTs and no CTs after normal x-rays. A prospective review was performed from 1/2017-6/2019. Pre and post guideline groups were compared. From 2013 to 2016, 246 patients met inclusion. 29.5% had a chest CT after a normal x-ray, only 1.8% (1/57) had a significant result. From 2017 to 2019, 188 patients were reviewed post guideline; only 9.4% received a CT after normal x-ray, of which 6.3% (1/16) were significant. Neither changed clinical management. Chest CT following normal chest x-ray does not change clinical management in pediatric trauma patients. Monitoring and education following guideline implementation improves long term outcomes.


Effect of experimental hyperinsulinaemia on intracellular glucose metabolism of isolated adipocytes.
Glucose oxidation and lipogenesis were studied in isolated adipocytes from control and non-obese, experimentally hyperinsulinaemic rats. In cells from the hyperinsulinaemic animals oxidation of either [1(-14) C]- or [6(-14) C] glucose was increased in the presence or absence of insulin, at substrate concentrations from 0.1 to 20 mmol/l. Glucose incorporation into total triglycerides and fatty acids was also increased. These enhanced rates of glucose metabolism were due to increased activity of the glucose transport system in addition to increased activity of intracellular glucose metabolism. Therefore, these data indicate that insulin can influence long term glucose homoeostasis by augmenting the overall cellular capacity for glucose metabolism at several loci.


Unusual ciliate-specific codons in Tetrahymena mRNAs are translated correctly in a rabbit reticulocyte lysate supplemented with a subcellular fraction from Tetrahymena.
The codon usage of Tetrahymena thermophila and other ciliates deviates from the 'universal genetic code' in that UAA and probably UAG are not translational termination signals but code for glutamine. Therefore, translation in vitro of mRNA from Tetrahymena in a reticulocyte lysate is prematurely terminated if a UAA or UAG triplet is present in the reading frame of the mRNA. We show that the addition of a subcellular fraction from Tetrahymena thermophila enables a rabbit reticulocyte lysate to translate Tetrahymena mRNAs into full-sized proteins. The activity of the subcellular fraction is shown to depend on the combined function of a protein component(s) and a tRNA(s). The subcellular fraction is easily prepared and its usefulness for the identification of isolated mRNAs from Tetrahymena by their translation products in vitro is demonstrated.


[Stimulation of neuropeptide Y on heat shock protein expression in renal vascular smooth muscle and the inhibition thereon by losartan].
To study the effect of neuropeptide Y (NPY) on the expression of heat shock protein 70 (HSP70) in vascular smooth muscle cells (VSMCs) of renal arteries. The renal veins of SD rats were isolated and broken into pieces. The VSMCs were cultured and then divided into 3 groups, neuropeptide Y (NPY), NPY + losartan, and serum-free DMEM were added into the culture respectively. Automated MTT colorimetric microassay and quantitative immunocytochemistry were used to detect the expression of heat shock protein (HSP70) in the proliferating VSMCs. The fluorescence intensity of labeled HPS70 in the NPY group was 1,825.10 +/- 115.55, significantly stronger than that in the control group (1595.83 +/- 186.54, P < 0.05) and the fluorescence intensity of labeled HPS70 in the NPY + losartan group (1 658.54 +/- 183.78) was not significantly different from that in the control group (P > 0.05). The MTT-OD in NPY group was 0.2626 +/- 0.0025, significantly higher than that in the control group (0.2239 +/- 0.0010, P < 0.01). and the MTT-OD in NPY + losartan group was 0.2440 +/- 0.0013, significantly lower than that in the control group (P < 0.05). NPY stimulates the proliferation of renal VSMC, promotes the expression of HPS70, and may cause hypertension. Losartan reduces the NPY stimulation over VSMC proliferation and relevant expression of intracellular HSP70.


Craniopharyngioma intrinsic to the third ventricle.
The case of a third ventricular craniopharyngioma in a 57-year-old woman is reported. This lesion is rare, having been previously identified in only eight adults. Intraventricular craniopharyngioma is also unusual in that it is not associated with tumoral calcification or cyst formation, as is frequently seen with the more common suprasellar craniopharyngioma. The role of computed tomography scanning in the diagnosis of this tumor is presented and discussed.


Renal cell carcinoma and vasculitis: report of two cases.
A 63-year-old caucasian male with systemic leukocytoclastic vasculitis involving the skin, lungs, and gastrointestinal tract was found to have a renal cell carcinoma at autopsy. A 77-year-old-woman with a history of hypertension was felt to have temporal arteritis that was confirmed by biopsy. The autopsy revealed a renal cell carcinoma in association with widespread giant cell arteritis. The possible association of renal cell carcinoma with vasculitis and an assessment of the possible clinical usefulness are presented and cases of vasculitis with renal neoplasms are briefly reviewed.


17β estradiol regulates adhesion molecule expression in mesangial cells during glomerulonephritis.
We showed previously that 17β estradiol (E2) led to improved survival in nephrotoxic serum induced nephritis (NTN) in male mice. In this study we determined whether E2 regulates vascular cell adhesion molecule (VCAM)-1, an adhesion molecule that is upregulated in kidney during autoimmune nephritis, in mesangial cells (MC). We show that E2 inhibited VCAM-1 up-regulation in kidneys in vivo during NTN, and in MCs upon TNFα stimulation. VCAM-1 up-regulation in MCs was controlled by the transcription factor NFκB. E2 inhibited RNA polymerase II recruitment to the VCAM-1 promoter, but not p65 recruitment. Interestingly E2 inhibited TNFα stimulated interaction between poly (ADP-ribose) polymerase-1 (PARP-1) and p65. As PARP-1 is required for VCAM-1 upregulation in MCs, our data suggest that E2 may inhibit pre-initiation complex formation at VCAM-1 promoter by inhibiting PARP-1 recruitment to p65. We propose that E2 plays an important role in regulating renal inflammation locally.


Exposure of field workers to organophosphorus insecticides: cotton.
The red blood cell and plasma cholinesterase (ChE) levels of cotton scouts inspecting foliage for insect infestation and damage were monitored. Group means for ChE activity were significantly depressed at one or more time(s) during four of the eight growing seasons studied. Although no symptoms of organophosphate poisoning were confirmed, several scouts exhibited ChE depressions over 50% of pre-exposure levels.


The influence of two cognitive-linguistic variables on incidental word learning in 5-year-olds.
The relation between incidental word learning and two cognitive-linguistic variables--phonological memory and phonological awareness--is not fully understood. Thirty-five typically developing, 5-year-old, preschool children participated in a study examining the association between phonological memory, phonological awareness, and incidental word learning. Children were exposed to target words in a read-aloud story that accompanied a wordless picture book. Target word comprehension was assessed before and after two readings of the story. Phonological awareness predicted incidental word learning but phonological memory did not. The influence of phonological awareness and phonological memory on word learning may be dependent on the demands of the word learning task.


Are urgent care centers a viable venue for recruitment in clinical trials?
Clinical trials are extremely difficult to undertake and recruiting patients for these trials is one of the most significant challenges. This brief report sought to determine the suitability of an urgent care center as a research recruitment site by assessing its patients' views on participating in clinical trials. One thousand and two subjects were surveyed over a 45-day period; 9.0 % had previously participated in clinical trials while 46.6 % indicated they would be interested in participating in future clinical trials if given the opportunity. This research suggests that the urgent care venue is a viable recruitment source for clinical trials.


Effects of sulfur on toxicity and bioavailability of Cu for castor (Ricinus communis L.) in Cu-contaminated soil.
The biogeochemical cycling of sulfur (S) in soil has an important impact on the bioavailability of heavy metals and affects the utilization of soil polluted by heavy metals. In addition, S-containing compounds are involved in heavy metal detoxification. This study investigated the effects of S on the toxicity and bioavailability of copper (Cu) in castor (Ricinus communis L.) grown in Cu-contaminated mine tailings. The results showed that the application of S reduced the accumulation of Cu in castor and promoted its growth. With the addition of S, the malondialdehyde (MDA) content of castor leaves decreased significantly compared with control plants, indicating the alleviation of oxidative stress. Superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) content decreased significantly with the alleviation of oxidative stress. The sequential extraction of Cu fractions showed that the application of S significantly reduced the reducible Cu fraction, and increased the oxidizable Cu fraction. It also increased the residual Cu fraction in the soil. The transformation of chemical speciation reduced the bioavailability of Cu in soil, which then reduced the accumulation of Cu in castor. Our results demonstrated that S application was effective at promoting castor growth by reducing the bioavailability and uptake of Cu in Cu-contaminated mine tailings.


The proxy effect: gender and gambling problem trajectories of iowa gambling treatment program participants.
Recent research has found that men and women who end up in gambling treatment tend to follow different trajectories to that endpoint: women generally begin gambling later in life, but progress to problems and seek treatment more quickly. With women's prevalence rates of gambling and disordered gambling increasing, it has become important to identify the causes and consequences of these trajectory differences. The current study used a sample of 2,256 gamblers enrolled in the Iowa Gambling Treatment Program to examine the relationship of gender and other demographic, economic and health-related (i.e., psychosocial) factors to empirically-identified gambling problem trajectories. The results indicated that gender made a statistically significant contribution to the prediction of trajectory, but increased predictive accuracy by only 1-2% beyond a model with psychosocial predictors. Gender's contribution was limited to its relationship to age of initiation; men and women's problem progression did not differ meaningfully once age of gambling initiation was taken into account. Gender is a unique contributor to the development of gambling problems among treatment seekers, but it is only one small part of the myriad psychosocial characteristics that influence gambling problem development.


Growth, development, puberty and adult height of patients with congenital multiple pituitary hormone deficiencies.
Congenital MPHD is a rare condition caused by mutations in pituitary transcription factors genes: PROP1, POU1F1 (PIT1), HESX1, LHX3, LHX4. We evaluated in a retrospective study the effects on growth and development in 29 patients with congenital MPHD (cMPHD), during hGH replacement therapy alone and combined with sex hormones. Twenty nine patients with cMPHD were included and diagnosed, treated and followed in our clinic from diagnosis to adult age. Measurements on growth and development were taken by the same medical team. Mean birth weight of 21/29 neonates was 3126 ± 536 g. Mean birth length of 7/29 neonates was 48.7 ± 2 cm. Neuromotor development was normal or slightly delayed. Mean age at referral was 9.5 ± 7 years (m), 6.7 ± 3.5 years (f) (p=0.17). Height (SDS) before treatment was -2.8 ± 1.0 (m), -2.8 ± 1.0 (f) (p=0.99). Mean age at initiation of hGH treatment was 9.9 ± 6.7 years (m), 10.3 ± 4.2 years (f) (p=0.85). Mean age at initiation of sex hormone treatment was 17.0 ± 3.5 years (m), 17.1 ± 2.3 years (f) (p=0.88). Penile and testicular sizes were below normal before and after treatment. Head circumference (SD) was -1.9 ± 0.9 before and -0.6 ± 1.8 at end of treatment (p<0.001). Adult height (SDS) reached -1.1 ± 0.6 (p<0.001) for both males and females. Despite the multiple pituitary hormone deficiencies including hGH, children with congenital MPHD present with a better auxological development than children with congenital IGHD or congenital IGF-1 deficiency. These findings may be due to irregular and incomplete hormone deficiencies increasing with progressive age and late initiation of puberty.


Differences in Non-suicidal Self-injury Behaviors between Unipolar Depression and Bipolar Depression in Adolescent Outpatients.
Non-suicidal self-injury (NSSI) has a higher prevalence in adolescents with depressive disorders than in community adolescents. This study examined the differences in NSSI behaviors between adolescents with unipolar depression (UD) and those with bipolar depression (BD). Adolescents with UD or BD were recruited from 20 general or psychiatric hospitals across China. The methods, frequency, and function of NSSI were assessed by Functional Assessment of Self-Mutilation. The Beck Suicide Ideation Scale was used to evaluate adolescents' suicidal ideation, and the 10-item Kessler Psychological Distress Scale to estimate the anxiety and depression symptoms. The UD group had higher levels of depression (19.16 vs.17.37, F=15.23, P<0.001) and anxiety symptoms (17.73 vs.16.70, F=5.00, P=0.026) than the BD group. Adolescents with BD had a longer course of NSSI than those with UD (2.00 vs.1.00 year, Z=-3.39, P=0.001). There were no statistical differences in the frequency and the number of methods of NSSI between the UD and BD groups. Depression (r=0.408, P<0.01) and anxiety (r=0.391, P<0.01) were significantly and positively related to NSSI frequency. Adolescents with BD had a longer course of NSSI than those with UD. More importantly, NSSI frequency were positively and strongly correlated with depression and anxiety symptoms, indicating the importance of adequate treatment of depression and anxiety in preventing and intervening adolescents' NSSI behaviors.


Total Synthesis of (-)-Enigmazole A.
A highly convergent, stereocontrolled total synthesis of the architecturally complex marine sponge metabolite (-)-enigmazole A has been achieved. Highlights include an unprecedented late-stage large-fragment Petasis-Ferrier union/rearrangement, a multicomponent Type I Anion Relay Chemistry (ARC) tactic, and a dithiane-epoxide union in conjunction with an oxazole-directed stereoselective reduction.


Behavioral Treatment of Insomnia and Sleep Disturbances in School-Aged Children and Adolescents.
Insomnia and related sleep disturbances are prevalent among youth and are associated with adverse consequences, including poorer psychiatric functioning. Behavioral sleep interventions, ranging from brief educational interventions to behavioral therapies (cognitive behavior therapy-insomnia), are associated with positive outcomes for pediatric sleep health. In addition, sleep interventions may improve psychiatric health for children and adolescents with neurodevelopmental and internalizing disorders. Additional research is necessary to clarify the efficacy of these interventions over the long-term and across demographic groups; however, evidence suggests incorporating behavioral sleep strategies may prove beneficial to pediatric patients with sleep disturbances and related psychiatric complaints.


Altered DNA methylation profiles in blood from patients with sporadic Creutzfeldt-Jakob disease.
Prion diseases are fatal and transmissible neurodegenerative disorders caused by the misfolding and aggregation of prion protein. Although recent studies have implicated epigenetic variation in common neurodegenerative disorders, no study has yet explored their role in human prion diseases. Here we profiled genome-wide blood DNA methylation in the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD). Our case-control study (n = 219), when accounting for differences in cell type composition between individuals, identified 38 probes at genome-wide significance (p < 1.24 × 10-7). Nine of these sites were taken forward in a replication study, performed in an independent case-control (n = 186) cohort using pyrosequencing. Sites in or close to FKBP5, AIM2 (2 probes), UHRF1, KCNAB2 successfully replicated. The blood-based DNA methylation signal was tissue- and disease-specific, in that the replicated probe signals were unchanged in case-control studies using sCJD frontal-cortex (n = 84), blood samples from patients with Alzheimer's disease, and from inherited and acquired prion diseases. Machine learning algorithms using blood DNA methylation array profiles accurately distinguished sCJD patients and controls. Finally, we identified sites whose methylation levels associated with prolonged survival in sCJD patients. Altogether, this study has identified a peripheral DNA methylation signature of sCJD with a variety of potential biomarker applications.


[Headache in childhood with special reference to migraine. Discussion of a personal case material of 94 subjects].
After having characterized epidemiologically, etiopathogenetically diagnostically, prognostically and psychologically the childhood headache, the A.A. refer data relative to 94 children of age in between 6 and 16 years, of which 51 females and 43 males, suffering for migraine (diagnosed by Bille's criteria). The ratio between migraine and sex, age, relationships, clinical symptomatology, onset time, crisis appearance frequency and causing factors have been studied. The relations between migraine and spasmophilia have been treated with particular remark in our casuistry, since similar studies don't appear in the literature. The work ends with some informations about migraine's common therapy, our particular one and the results that we obtained.


Complete genome sequence of GII.9 norovirus.
Norovirus is recognized as one of the leading causes of acute gastroenteritis outbreaks. Genotype GII.9 was first detected in Norfolk, VA, USA, in 1997. However, the complete genome sequence of this genotype has not yet been determined. In this study, a complete genome sequence of GII.9[P7] norovirus, SCD1878_GII.9[P7], from a patient was determined using high-throughput sequencing and rapid amplification of cDNA ends (RACE) technology. The complete genome sequence of SCD1878_GII.9[P7] is 7544 nucleotides (nt) in length with a 3' poly(A) tail and contains three open reading frames. Sequence comparisons indicated that SCD1878_GII.9[P7] shares 92.1%-92.3% nucleotide sequence identity with GII.P7 (AB258331 and AB039777) and 96.7%-97.4% identity with GII.9 (AY038599 and DQ379715). The results suggested that SCD1878_GII.9[P7] is a member of P genotype GII.P7 and G genotype GII.9. This viral sequence fills a gap at the whole-genome level for the GII.9 genotype.