Improving understanding and management of the complex relationship between visitor motivations and spatial behaviors in parks and protected areas.
Increases in use and changes in the behavior of visitors to parks and protected areas (PPAs) worldwide are challenging the ability of managers to provide for a quality visitor experience while also maintaining the integrity of natural resources. Understanding visitor motivations and spatial behaviors are important for effective management of PPA resources and visitor experiences, as differences in motivations and spatial behaviors can influence the distribution of impacts to a recreation landscape. However, the relationships between motivations and behaviors are not well understood. In this study, we investigated the relationship between motivations and spatial behavior patterns of recreationists within a system of urban and peri-urban PPAs in Orange County, California, USA. Data were collected using paired GPS-based tracking and visitor questionnaires. Factor analysis revealed seven primary motivations derived from a 36-item motivation scale, and classification of visitors by motivations suggests two primary types. A three-way Analysis of Variance examining the relationship between a suite of visitor spatial behaviors and activity type (mountain bike vs. pedestrian), motivation type, and recreation area visited showed that all three variables interacted to influence visitor spatial behavior patterns while recreating. A spatial analysis of visitor dispersion further illustrated these interactions. These results suggest that the relationship between visitor motivations and spatial behaviors is complex. Understanding the complexities of how motivations influence visitor spatial behavior can help land managers mitigate impacts and improve planning for outdoor recreation by predicting where use may increase, how visitors might behave, and highlight locations of future research.


Spatial memory deficits following stimulation of hippocampal 5-HT1B receptors in the rat.
In this study we examined a possible contribution of serotonin (5-hydroxytryptamine, 5-HT) to spatial memory performance in the rat. Rats were trained to run in a radial maze in a manner that involved two kinds of memory function, i.e. working memory and reference memory. They received intrahippocampal microinjections of a 5-HT1A [8-hydroxy-2-(di-n-propylamino)tetralin or 8-OH-DPAT], or a 5-HT1B [3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one or CP-93,129] receptor agonist, and a muscarinic receptor antagonist (scopolamine). 8-OH-DPAT (5 micrograms/microliters), like injections of saline, induced no change in performance levels. In contrast, rats suffered an impairment in both reference and working memory following injection of scopolamine (10 micrograms/microliters). CP-93,129 induced a higher frequency of reference memory errors than of working memory errors at the intermediate (10 micrograms/microliters) and higher doses (16 micrograms/microliters). Thus, the stimulation of 5-HT1B receptors in the CA1 field of the dorsal hippocampus impairs the performance of rats in a spatial learning task.


Green synthesis of modified polyethylene packing supported tea polyphenols-NZVI for nitrate removal from wastewater: Characterization and mechanisms.
Nano-zero-valent iron (NZVI), as an electron donor, performed excellence in the reduction and remove of nitrate. However, the easy agglomeration and poor antioxidation of NZVI declined the nitrate removal and limited the application in the field of wastewater treatment. Herein, a novel composite packing of tea polyphenol, NZVI and modified polyethylene carrier (TP-NZVI/PE) was prepared and characterized, the removal efficiency of nitrate was verified, and the preliminary removal mechanism was finally investigated. The results showed that the maximum iron loading on TP-NZVI/PE composite achieved under 50 °C, pH of 5.0, 4.0 g/L of Fe2+, and 7.2 g/L of TP, respectively, with 3.51 ± 0.12 mg/g. NZVI presented satisfactory antioxidation and anti-agglomeration via TP encapsulation. TP encapsulation of TP-NZVI/PE composite was easily degraded by microorganisms and NZVI was exposed to nitrate during wastewater treatment, which made the reduction of nitrate possible. The nitrate removal efficiency of TP-NZVI/PE composite with microorganism was 79.88 ± 0.17%, higher three times than that of TP-NZVI/PE (25.54 ± 0.21%). The oxidized NZVI was transformed to Fe2+/Fe3+, which were prone to adsorb nitrate and then co-precipitate. It was favorable for further removal of nitrate. Results suggested a novel approach for fast and eco-friendly preparation and efficient application of NZVI.


The efficacy and safety of continuous versus single-injection popliteal sciatic nerve block in outpatient foot and ankle surgery: a systematic review and meta-analysis.
Continuous popliteal sciatic nerve block (CPSNB) has been performed in outpatient foot and ankle surgery as a regional anesthesia method to relieve postoperative pain. Its efficacy as well as safety is yet to be established. There are two purposes of this study: (1) to validate the efficacy of CPSNB with regards to better pain relief and reduced analgesics consumption; (2) to assess the safety of CPSNB. We performed a comprehensive literature review on Web of Science, the Cochrane Library, PubMed and Embase and only included randomized controlled trials (RCTs). Five RCTs that compared the efficacy and safety of CPSNB with the single-injection popliteal sciatic nerve block group were included. The primary outcome parameters were visual analog scale (VAS) scores at postoperative 24, 48 and 72 h. The secondary outcome parameters were amount of oral analgesics consumed, overall patient satisfaction and need of admission after surgery. A sensitivity analysis was performed to explore the consistency of the results. In comparison with the single-injection group, CPSNB was associated with a lower VAS score at postoperative 24 and 48 h (p < 0.05). There were no neuropathic symptoms or infection events after the nerve block. However, there were several minor complications associated with the pump and catheter system, with drug leakage being the most common complication (N = 26 of 187, 13.9%). CPSNB is an effective method in pain management for outpatient foot and ankle surgery. Both methods appear to be safe as none of the patients experienced neuropathic symptoms or infection. Further studies with larger sample size are needed to compare the risk of major complications between the two methods. I; meta-analysis.


Tumor angiogenesis as a prognostic factor in laryngeal cancer.
Lymph node metastasis is the single greatest predictor of recurrence in laryngeal cancer. Prognostic factors are needed to target patients who may benefit from adjuvant therapy. Tumor angiogenesis correlates with metastasis in breast, bladder, and oral cavity cancer and may have prognostic value in other tumors. In order to examine the relationship of tumor angiogenesis to recurrence, 51 patients with squamous cell carcinoma of the larynx were reviewed. In a blinded design, previously sectioned slides were chosen for advanced tumor and highest vessel concentration. Samples were cut and immunocytochemically stained for CD-31 (an endothelial marker). A computer image analyzer quantitated the percent area of staining. Variables were statistically examined against recurrence. Patients were stratified by percent tumor staining. Nodal involvement was seen in 9 (36%) patients with tumor staining < or = 20% and in 20 (77%) with tumor staining > 20% (P = 0.003). Patients with < or = 20% staining and without metastasis had a 13% rate of recurrence whereas patients with > 20% staining and without metastasis had a 67% rate of recurrence (P = 0.025). Though nodal status was suggestive of predictability, only angiogenesis is a statistically significant predictor of recurrence in node negative patients (P = 0.025). Angiogenesis shows strong correlation with regional recurrence and may be used as an independent prognostic indicator to determine clinically node negative patients who may be at higher risk for metastasis and require adjuvant therapy.


[Development of a screening workflow to identify patient needs in an interdisciplinary oncological day clinic].
The diagnosis of cancer leads to high levels of emotional distress in many patients. Quality of life is an important therapeutic goal in this context. A quality-of-life guide was implemented in the oncological day clinic (ICT) at the University Hospital of Regensburg (UKR) in order to individually support outpatients, help them with their questions and needs and improve their quality of life. A screening tool is necessary for the structured assessment of quality of life/needs in the routine of tumor therapy and follow-up. As part of a mixed-methods study, focus groups with health professionals/patients were organized to specify the needs of cancer patients. On this basis, the literature was searched for questionnaires covering these needs in order to adapt an ICT-specific questionnaire and integrate it with the help of a workflow. A total of 333 individual aspects were brought up by the participants in focus groups on the needs of cancer patients in various phases of treatment/with various tumor entities. Since none of the questionnaires identified in the literature met our requirements, a new screening tool containing elements from different standardized forms and the results of the focus groups was developed and a new workflow created to integrate the questionnaire into the ICT routine. By interviewing health experts from different areas and patients with different tumor entities, the needs of cancer patients over different stages of the disease and additional possible differences between the cancer entities were identified and recorded. Through the implementation of a quality-of-life guide in the ICT, a structured assessment of the quality of life and an analysis of patient needs can take place with the help of the screening. A workflow was created to integrate screening into routine care. In addition, the questionnaire was designed in such a way that it can be used repeatedly at various points in time. In order to cover important stages in the course of therapy and to determine how patient needs change over the course, patients should be asked to complete the questionnaire several times after specified time intervals. The questionnaire is intended to assess the needs of cancer patients receiving outpatient treatment in a structured manner. Now it needs to be explored how the new screening tool and workflow interact and perform in clinical practice and how they help to improve patients' quality of life. It is also interesting to analyze which patients accept the advice offered by the quality-of-life guide and which needs are expressed most frequently.


Measuring relatives' perspectives on the quality of palliative care: the Consumer Quality Index Palliative Care.
A Consumer Quality Index (CQ-index) is a questionnaire assessing the actual care experiences and how important the recipient finds certain care aspects, as well as the priorities for improving quality. A CQ-index Palliative Care (CQ-index PC) for bereaved relatives was developed to measure the quality of palliative care. This article provides insight into the development and psychometric characteristics of this questionnaire, as well as quality improvement priorities. The content of the CQ-index PC was based on existing questionnaires, literature, and interviews and focus group discussions with relatives, patients, and caregivers. The questionnaire was tested in 31 care facilities providing palliative care. Close relatives/contact persons of patients who died non-suddenly six weeks to six months earlier were eligible for inclusion. Psychometric analyses were performed to shorten the questionnaire and to assess its reliability. "Need for improvement scores" also were computed to identify care aspects with the highest priority for quality improvement. Three hundred ninety-two bereaved relatives were eligible for inclusion. The net response was 52% (n=204). Psychometric analyses resulted in six scales (Cronbach's alphas ranging from 0.71 to 0.90). The quality aspects relatives considered most important were dying peacefully, getting help in good time in acute situations, and personal attention. Aftercare was the aspect with the highest priority for quality improvement. The CQ-index PC for relatives can be used to assess the quality of palliative care from the perspective of bereaved relatives. This instrument gives health care professionals insight into care aspects with the highest priority for quality improvement.


Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients.
To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC). Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)-pulmonary embolus, 1 (4%)-febrile neutropenia, and 1 (4%)-infection; grade 3 toxicities were 4 (15%)-neutropenia, 4 (15%)-fatigue, 2 (7%)-neuropathy, 2 (7%)-athralgias, 2 (7%)-stomatitis, 1 (7%)-pleural effusion, and 1 (4%)-hypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.


Rchimerism: An R Package for Automated Chimerism Data Analysis.
A quantitative chimerism test monitors engraftment of donor hematopoietic stem cells or relapse of leukemias or lymphomas in hematopoietic stem cell transplantation patients. The most common method used for chimerism testing is PCR amplification of short tandem repeat loci, followed by capillary gel electrophoresis. Manual data analysis is tedious and time consuming, as it involves the selection of informative loci and the repetition of quantifying chimerism percentage for multiple loci from multiple cell types. It is also susceptible to human errors. Currently, there is no free software to fully automate chimerism data analysis. Rchimerism, an R shiny package, was developed to automatically pick informative loci, calculate chimerism percentage, and display the results through a user-friendly interface. The accuracy of the program was compared with manual calculation on 60 patient samples with 100% concordance. Compared with manual calculation, Rchimerism drastically reduces analysis time from 20 to 40 minutes for single donor transplantation samples and from 40 to 80 minutes for double donor transplantation samples to >1 minute. Rchimerism can be downloaded and used freely by noncommercial laboratories.


Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell immune-dysregulation and loss of tolerance to self-antigens. CTLA-4 and PTPN-22 are involved in the inhibition of T-lymphocytes activation. IL-37 is an anti-inflammatory cytokine that suppresses innate immunity. The relative expression of CTLA-4, IL-37 and PTPN-22 were evaluated as negative regulators of immune response in SLE patients, lupus nephritis (LN) and disease activity. Real-Time PCR was performed to determine relative CTLA-4, IL-37, and PTPN-22 mRNA expressions in fifty-eight SLE patients, who were divided into two groups: 29 SLE patients without nephritis and 29 patients with LN, versus fifty controls. There was a significantly high-expression of CTLA-4 and IL-37 genes in SLE patients compared to controls (p=0.005; 0.018 respectively). There was no difference in relative PTPN-22 mRNA expression between the SLE patients and controls. Relative CTLA-4 mRNA expression decreased in LN patients (p=0.044), however, relative IL-37 mRNA over-expressed in LN patients (p=0.001) compared to those without LN. There was a significant over-expression of relative IL-37 andPTPN-22 mRNA in active SLE patients. But, there was a non-significant difference in CTLA-4 expression with disease activity. Regression analysis revealed patients with relative IL-37 mRNA over-expression had two times more to develop lupus nephritis (OR=1.906, 95% CI=1.218-2.983, p=0.005). Relative IL-37mRNA expression was elevated in SLE patients and associated with renal involvement and disease activity. It could be considered as a new promising predicting tool for LN. Relative PTPN-22 mRNA expression was correlated with disease activity only in SLE patients.


Intensity of X-ray reflections from skeletal muscle thin filaments partially occupied with myosin heads: effect of cooperative binding.
For quantitative analysis of contractile proteins of muscle by means of X-ray diffraction, it is important to know how the intensities of individual reflections are related to the number of diffracting objects, i.e., the amount of constituent contractile protein in the muscle cell. Here we diffused various amounts of exogenous myosin subfragment-1 (S1) into overstretched skinned skeletal muscle fibers, either in the presence or absence of Ca2+ , and derived the relationship between the S1 content and the intensities of reflections arising from the S1. In theory, the intensities should be proportional to the square of the S1 content (square law). However, the intensity-content relation deviated systematically from the square law as the S1 content was lowered, and it was better described as a linear function at the lower end of the S1 contents (<20% of saturation level). Model calculations show that the way of deviation is explained by the cooperative manner of S1 binding to the regulated thin filament.


Suppression of motor seizures after specific thalamotomy in chronic epileptic monkeys.
In the monkey with a chronic motor epileptogenic focus, thalamic lesions restricted to the anterior part of the ventro-postero-lateral nucleus produced a long-lasting improvement, leading in most cases to almost complete seizure suppression. This improvement was attributed to the interruption of a long-loop recurrent excitatory mechanism, involving muscular afferents which are known to relay in the thalamic region where lesions were produced. The specific nature of this effect was suggested by the preliminary results of lesions performed in thalamic regions with non-specific cortical projections. Compared with the pre-lesional situation in which focal activity resulted in permanent motor troubles, the post-lesional state did not show any additional motor deficit. It is concluded that such lesions could be a new approach to controlling intractable motor epilepsies in man.


Protective role of antibodies induced by Brucella melitensis B115 against B. melitensis and Brucella abortus infections in mice.
It has been demonstrated that antibodies specific for O-PS antigen of Brucella smooth strains are involved in the protective immunity of brucellosis. Since the rough strain Brucella melitensis B115 was able to protect mice against wild Brucella strains brucellosis despite the lack of anti-OPS antibodies, in this study we evaluated the biological significance of antibodies induced by this strain, directed to antigens other than O-PS, passively tranferred to untreated mice prior to infection with Brucella abortus 2308 and B. melitensis 16M virulent strains. The protective ability of specific antisera collected from mice vaccinated with B. melitensis B115, B. abortus RB51 and B. abortus S19 strains was compared. The results indicated that antibodies induced by B115 were able to confer a satisfactory protection, especially against B. abortus 2308, similar to that conferred by the antiserum S19, while the RB51 antiserum was ineffective. These findings suggest that antibodies induced by B115 could act as opsonins as well as antibodies anti-O-PS, thus triggering more efficient internalization and degradation of bacteria within phagocytes. This is the first study assessing the efficacy of antibodies directed to antigens other than O-PS in the course of brucellosis infection.


Characteristics of depressed and non-depressed children and their parents.
A sample of 186 outpatient children considered by both clinicians and parents as depressed or non-depressed were compared in terms of child and parent variables. Parents of depressed children appeared to be more overinvolved with their children, more overprotective, more likely to have communication difficulties in the family and more apt to undermine the child's learning. More girls were depressed than boys and depressed children exhibited more somatic complaints and coexisting phobic or anxiety disorders. The results of the present study need to be replicated with a broader group of depressed and non-depressed children and their families from other regions of the country. Further research in this area is indicated in order to provide clinicians who work with depressed children with a better understanding of their symptoms and parental characteristics.


Stabilization of the Metastable α-Form of Indomethacin Induced by the Addition of 2-Hydroxypropyl-β-Cyclodextrin, Causing Supersaturation (Spring) and Its Sustaining Deployment (Parachute).
The purpose of this study is to find that a small amount of 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) can produce a parachute effect on indomethacin (INM). From the examination of dissolution curves and concentration after several days, the supersaturation of INM was observed for the mixtures containing HP-β-CD at a molar ratio ≤ 0.5, and the sustained deployment of supersaturation was found not only in equimolar mixtures but also in mixtures with a shortage of HP-β-CD. In the solid state, it was compared the physical properties of INM/HP-β-CD mixtures using two different mixing methods and determined the stoichiometry of INM and HP-β-CD. Differential scanning calorimetry (DSC) revealed that the polymorphs of INM were converted by HP-β-CD into an amorphous state. Furthermore, X-ray powder diffraction (XRPD) and DSC-XRPD demonstrated that INM crystals from the INM/HP-β-CD mixture prepared from an EtOH solution were metastable. In conclusion, these phenomena may be considered the "spring" and "parachute" effects of mixtures with a shortage of HP-β-CD, as they depended on the presence of the metastable α-form of INM. The addition of 1/3 to 1/20 equivalents of HP-β-CD to INM enhanced INM solubility.


EU MECI: A Network-Structured Indicator for a Union of Equality.
How are the Member States performing in their challenge toward a fairer and more equal Europe? Based on the data measured by the EU Multidimensional Inequality Monitoring Framework (EU MIMF), we introduce the Multidimensional Equality Complexity Index, EU MECI, derived by structuring the EU MIMF data as a bipartite network of countries and indicators. EU MECI is defined upon the economic complexity methodology, exploiting the network's centrality metrics to calculate aggregate scores of the capacity of Member States to 'build a Union of equality'.


Toward an integrative model of the spectrum of mood, behavioral and personality disorders based on fear and anger traits: II. Implications for neurobiology, genetics and psychopharmacological treatment.
Current psychiatry relies on a purely categorical paradigm for diagnosis of mental disorders that profoundly impacts research and clinical practice. However, high comorbidity rates and relative non-specificity of family history for psychiatric disorders suggests that this categorical approach fails to identify the underlying diathesis. As an attempt to overcome such limitations, we developed a bidimensional model based on fear and anger traits or temperaments which does not preclude the use of a categorical approach. As a result, it is hypothesized that mood, behavioral and personality disorders share a neurobiological substrate according to combinations of fear and anger traits. Both fear and anger, when excessive or deficient, lead to increased risk for mental disorders and should be considered in genetic, neurobiological and neuroimaging studies. Fear traits are much influenced by the amygdala and the serotonergic, noradrenergic and GABAergic systems, whereas anger seems to be mostly regulated by the nucleus accumbens and the dopaminergic and glutamatergic systems. Pharmacological treatments with antidepressants and anxiolytics can be considered as essentially restraint on fear, whereas lithium and alpha2 noradrenergic agonists would attenuate fear deficiency. Dopaminergic antidepressants and psychostimulants are anger enhancers and antipsychotics and mood stabilizers, such as divalproate and carbamazepine, may share antianger effects. Drugs effective for manic and depressive phases probably have both antianger and antifear effects. This framework may lead to a better understanding of the neurobiological basis of mental health and disease, providing an integrative approach for future research.


Coordinated transcription of key pathways in the mouse by the circadian clock.
In mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed approximately 650 cycling transcripts and showed that the majority of these were specific to either the SCN or the liver. Genetic and genomic analysis suggests that a relatively small number of output genes are directly regulated by core oscillator components. Major processes regulated by the SCN and liver were found to be under circadian regulation. Importantly, rate-limiting steps in these various pathways were key sites of circadian control, highlighting the fundamental role that circadian clocks play in cellular and organismal physiology.


Analgesia for operative dentistry: a comparison of acupuncture and placebo.
Fifty-one volunteer patients participated in a study to evaluate the effectiveness of acupuncture as an analgesic for operative dentistry. For the twenty-six patients randomly assigned to an acupuncture group, needles were inserted through specially designed holders into the Ho-Ku points, located between the first and second metacarpals. An acupuncture pulse generator provided electrical current. For the twenty-five patients in a placebo group, the identical needle and holder arrangement was used. When inserted, however, the needles became embedded in plastic on the undersurface of the holders and did not touch the skin of the patient or receive any electrical stimulation. The patients and dentists were blind to this procedural variation. Analysis of ratings and responses indicated no differences in findings for the acupuncture and placebo procedures, with both having 100% success and high levels of patient acceptance. Since there was no electric current or penetration of the skin in the placebo group, the findings suggest that the successful use of acupuncture for restorative dentistry may be due to psychological and/or placebo effects in combination with a possible diminished need for analgesia because of the modern use of the high-speed drill.


Patient-Related Risk Factors for Contralateral Anterior Cruciate Ligament (ACL) Tear After ACL Reconstruction: An Analysis of 3707 Primary ACL Reconstructions.
Return to play after anterior cruciate ligament (ACL) reconstruction can increase risk for both ipsilateral graft rupture and contralateral ACL rupture. The risk for injury of the contralateral knee after ACL reconstruction could be nearly double that of ipsilateral graft rupture. We sought to identify independent, patient-related risk factors for contralateral ACL rupture following primary ACL reconstruction. A national database was queried for patients who underwent primary ACL reconstruction from 2007 to 2015 with a minimum of 2 years of post-operative follow-up (n = 12,044). Patients who underwent subsequent primary ACL reconstruction on the contralateral extremity were then identified. A multivariate binomial logistic regression analysis was utilized to evaluate patient-related risk factors for contralateral ACL rupture, including demographic and comorbidity variables. Adjusted odds ratios and 95% confidence intervals were calculated for each risk factor. Of the 3707 patients who had a minimum of 2 years of database activity and comprised the study group, 204 (5.5%) experienced a contralateral ACL rupture requiring reconstruction. Independent risk factors for contralateral ACL rupture included age less than 20 years, female gender, tobacco use, and depression. Obesity, morbid obesity, type 1 diabetes, type 2 diabetes, and a history of anxiety were not significant predictors of contralateral injury. We were able to adequately power an analysis to identify several significant patient-related risk factors for contralateral ACL rupture after primary ACL reconstruction, including younger age, female gender, tobacco use, and depression. This information can be used to counsel patients on the risk of injury to the contralateral knee.


Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study.
• To investigate androgen receptor (AR) expression in a large series of patients with bladder cancer (BC) because data on a limited number of patients showed that loss of AR expression was associated with invasive BC. • A total of 472 patients with urothelial bladder carcinoma (UBC) from two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays comprising both non-muscle-invasive UBC (n= 167) and muscle-invasive UBC (n= 305) were accrued and immunohistochemical staining for AR was performed. • We used bright-field microscopy imaging coupled with advanced colour detection software to detect, classify and count stained cellular objects and manual scoring. • Results obtained in Dallas were blindly reviewed and validated in Toronto and samples randomly chosen were further analysed in Rochester, NY, USA. • The AR were positively expressed in 61/472 (12.9%) bladder tumours. No statistically significant difference in AR expression between men and women was observed. • Only 9.0% of non-muscle-invasive BC expressed the AR compared with 15.1% of muscle-invasive tumours (P= 0.059). The highest percentage of AR positivity (28.9% of cases) was found in T2 tumours. • There was no statistically significant difference in death from BC, time to death, or time to recurrence between AR-positive and AR-negative cases. • In contrast to previous reports, based on our large BC series, we did not observe a decrease in AR protein expression in bladder tumours with increased pathological stage. Our data do not suggest that loss of AR expression is gender-related nor is it associated with invasive BC.


In Vitro Efficacy for Chlorpyrifos Degradation by Novel Isolate Tistrella sp. AUC10 Isolated from Chlorpyrifos Contaminated Field.
Chlorpyrifos, an organophosphate (OP) pesticide, possess broad-spectrum insecticidal activity against Lepidoptera, Diptera, Homoptera, Coleoptera, Orthoptera, Hymenoptera, and Hemiptera. Organophosphate pesticides have acute neurotoxicity because they suppress acetylcholine esterase (AChE) which regulates the enzyme of neurotransmitters by reducing acetylcholine concentration at synaptic junctions. On exposure to OP, AChE is inactivated and leads to accumulation of acetylcholine in the junction. Moreover, due to their persistence nature they biomagnify at different food chain levels. In the present study, a newly isolated indigenous bacterial strain Tistrella sp. AUC10 was exploited for its ability to degrade chlorpyrifos pesticide. The isolate completely degrades (99.86%) chlorpyrifos. The degraded metabolites of chlorpyrifos by Tistrella sp. AUC10 were identified by GC-MS analysis. Based on the GC-MS analysis, a putative pathway of degradation of chlorpyrifos by Tistrella sp. AUC10 has been proposed. It emulsified various hydrocarbons and also confirms biosurfactant production on CTAB agar. This study is the first report on elucidation of the mechanism of degradation of chlorpyrifos by Tistrella sp. Furthermore, phytotoxicity studies of the parent compound and the biodegraded chlorpyrifos products revealed drastic reduction in the toxicity of metabolites as compared to the parent chlorpyrifos. This implies that the biodegraded metabolites of chlorpyrifos are of non-toxic nature. This study thus indicates the efficacy of Tistrella sp. AUC10 for the treatment of chlorpyrifos contaminated agricultural fields.


Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking.
Benzothiazole derivatives 1-26 have been synthesized and their in vitro β-glucuronidase potential has been evaluated. Compounds 4 (IC(50)=8.9 ± 0.25 μM), 5 (IC(50)=36.1 ± 1.80 μM), 8 (IC(50)=8.9 ± 0.38 μM), 13 (IC(50)=19.4 ± 1.00 μM), 16 (IC(50)=4.23 ± 0.054 μM), and 18 (IC(50)=2.26 ± 0.06 μM) showed β-glucuronidase activity potent than the standard (d-saccharic acid 1,4-lactone, IC(50)=48.4 ± 1.25 μM). Compound 9 (IC(50)=94.0 ± 4.16 μM) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the gold 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of β-glucuronidase inhibitors.


Updated estimates of eligibility for and response to genome-targeted oncology drugs among US cancer patients, 2006-2020.
Prior studies have evaluated the percentage of cancer patients with advanced or metastatic cancer who are eligible for and respond to genome-targeted therapy, but since that publication, the number of Food and Drug Administration (FDA) approvals for drugs targeting genetic indications has grown rapidly. We sought to update the estimates of both eligibility for and response to genome-targeted and genome-informed therapies in US cancer patients for FDA-approved drugs to reflect estimates as of 2020. We used mortality data from the American Cancer Society to estimate eligibility for these drugs, based on prevalence statistics from the published literature. We then multiplied eligibility by the response rate in the FDA label to generate an estimate for the percentage of US cancer patients who respond. For genome-targeted therapy, we estimate that the eligibility increased from 5.13% in 2006 to 13.60% in 2020. For genome-targeted therapy, we estimate that the response increased from 2.73% in 2006 to 7.04% in 2020. The percentage of US cancer patients who are eligible for and respond to genome-targeted therapy has increased over time. Most of the increase in eligibility for genome-targeted therapies was seen after 2018, whereas most of the increase in response was seen before 2018.


Simulating PFAS adsorption kinetics, adsorption isotherms, and nonideal transport in saturated soil with tempered one-sided stable density (TOSD) based models.
Reliable quantification of per- and polyfluoroalkyl substances (PFAS) adsorption and mobility in geomedia provides critical information (i.e., evaluation and prediction) for risk characterization and mitigation strategy development. Given the limited PFAS data available and various competing theories for modeling pollutant kinetics, it is indispensable to better understand and quantify the adsorption and transport of PFAS in geomedia using generalized models built upon a consistent physical theory. This study proposed a universal physical law (called the tempered stable law) in PFAS adsorption/transport by interpreting PFAS adsorption kinetics and nonideal transport as a nonequilibrium process dominated by adsorption/desorption with multiple rates following the tempered one-sided stable density (TOSD) distribution. This universal TOSD function led to novel TOSD-based models which were then tested by successfully simulating PFAS adsorption kinetics, adsorption isotherms, and nonideal transport data reported in the literature. Model comparisons and extensions were also discussed to further check the feasibility of the TOSD models and their adaptability to capture PFAS transport in more complex geomedia at all scales.


Benefits equity. Providers anticipate core mental health coverage.
In recent years, payer restrictions have led to many belt-tightening measures in the psychiatric field. But word that the administration may expand mental health insurance coverage has provided a needed shot in the arm for that field.


Composition and duties of local boards of health: findings from a 2011 national survey.
To describe the composition and duties of local boards of health (LBOHs). An online and written survey was utilized for data collection. The survey included demographics, roles and responsibilities, orientation and training, and concerns and needs of LBOHs. This article seeks to expand what limited information we have on the composition and duties of LBOHs as an important foundational step in analyzing the role of LBOHs in leveraging improved public health outcomes. In 2011, the mixed methods survey was sent to a random sample of 2420 LBOHs in the 41 states, which meet the definition of having LBOHs. The data represent responses from 353 LBOHs in 35 states. Elected officials appoint members of 68% of LBOHs. The average board consists of a 7-member, county-based LBOH made up primarily of males (60%) and whites (96%). Hispanics make up 9% of boards. The majority of LBOH chairs have a graduate degree but no formal education or experience in public health. Local boards of health report reviewing public health regulations as their most common power but list recommending the approval of the budget for the local health department as boards' most frequent activity in the past 3 years. LBOH members and chairs are more similar in demographics to the top executives at local health departments than the general population or the public health workforce. Most LBOH chairs, however, lack experience in public health, and a quarter or more of LBOHs do not use their powers to set or recommend health priorities as a mechanism to leverage better community health outcomes.


Two cases of cardiomyopathy associated with phaeochromocytoma successfully managed with veno-arterial extracorporeal membrane oxygenation (V-A ECMO).
Phaeochromocytoma, a rare neuroendocrine tumour of chromaffin cell origin, is characterised by catecholamine excess. Clinical presentation ranges from asymptomatic disease to life-threatening multiorgan dysfunction. Catecholamine-induced cardiomyopathy is a dreaded complication with high lethality. While there is lack of evidence-based guidelines for use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) in the management of this condition, limited to case reports and small case series, V-A ECMO has been reported as 'bridge to recovery' therapy, providing circulatory support in the initial period of stabilisation prior to surgery. We report on two patients presenting with catecholamine-induced cardiomyopathy and circulatory collapse who were successfully treated with V-A ECMO for 5 and 6 days, respectively, providing initial haemodynamic support. After stabilisation and introduction of alpha-blockade, both cases had favourable outcomes, with successful laparoscopic adrenalectomies on days 62 and 83 of admission, respectively. Our case reports provide further support for the use of V-A ECMO in the treatment of such gravely ill patients. Phaeochromocytoma should be considered in the diagnosis of patients presenting with acute cardiomyopathy. Management of catecholamine-induced cardiomyopathy is complex and requires multidisciplinary specialist input. Pre-operative management of phaeochromocytoma involves alpha-blockade; however, haemodynamic instability in the setting of cardiogenic shock can preclude alpha-blockade use. Veno-arterial extracorporeal membrane oxygenation is a life-saving intervention which may be considered in cases of acute catecholamine-induced cardiomyopathy and cardiogenic shock in order to provide the required haemodynamic support in the initial phase of treatment, enabling the administration of traditional pharmacological agents, including alpha-blockade.


Correction: Good citizens, perfect patients, and family reputation: Stigma and prolonged isolation in people with drug-resistant tuberculosis in Vietnam.
[This corrects the article DOI: 10.1371/journal.pgph.0000681.].


Lessons learned from evolving frameworks in adult glioblastoma.
Glioblastoma (GBM) is the most common and aggressive malignant adult brain tumor. Significant effort has been directed to achieve a molecular subtyping of GBM to impact treatment. The discovery of new unique molecular alterations has resulted in a more effective classification of tumors and has opened the door to subtype-specific therapeutic targets. Morphologically identical GBM may have different genetic, epigenetic, and transcriptomic alterations and therefore different progression trajectories and response to treatments. With a transition to molecularly guided diagnosis, there is now a potential to personalize and successfully manage this tumor type to improve outcomes. The steps to achieve subtype-specific molecular signatures can be extrapolated to other neuroproliferative as well as neurodegenerative disorders.


[Imaging of the anterior abdominal wall: ultrasonography and CT features].
US and CT have both become major tools in imaging of the anterior abdominal wall. The goal of this pictorial review is to illustrate the respective roles of US and CT in the evaluation of normal and abnormal anterior abdominal wall.


[Th1/Th2 immune response in bronchoalveolar lavage fluid in children with severe Mycoplasma pneumoniae pneumonia].
To study the status of Th1/Th2 immune response and the value of the detection of cytokines in bronchoalveolar lavage fluids (BALF) by examining the levels of IFN-γ and IL-4 in BALF and serum in children with severe Mycoplasma pneumonia (MPP). The levels of IFN-γ and IL-4 in BALF and serum were measured using ELISA in 25 children with severe MPP, 25 children with mild MPP and 25 children with foreign body in bronchus. The levels of IL-4 and IFN-γ and the IL-4/IFN-γ ratio in BALF in children with severe MPP were significantly higher than those in children with foreign body in bronchus (P<0.01 or P<0.05). The serum levels of IL-4 and the IL-4/IFN-γ ratio in children with severe MPP were significantly higher than those in children with foreign body in bronchus (P<0.01) or with mild MPP (P<0.05). The levels of IL-4 and the IL-4/IFN-γ ratio in BALF were significantly higher than in serum (P<0.05). The data suggest that the imbalance of Th1/Th2 exists in children with severe MPP and it seems to represent a predominant Th2-like cytokine response. The detection of cytokines in BALF appears to be more sensitive than in serum and may be of value in the diagnosis and therapy of MPP.


Plasticity of glomeruli and olfactory-mediated behavior in zebrafish following detergent lesioning of the olfactory epithelium.
The zebrafish olfactory system is a valuable model for examining neural regeneration after damage due to the remarkable plasticity of this sensory system and of fish species. We applied detergent to the olfactory organ and examined the effects on both morphology and function of the olfactory system in adult zebrafish. Olfactory organs were treated once with Triton X-100 unilaterally to study glomerular innervation patterns or bilaterally to study odor detection. Fish were allowed to recover for 4-10 days and were compared to untreated control fish. Axonal projections were analyzed using whole mount immunocytochemistry with anti-keyhole limpet hemocyanin, a marker of olfactory axons in teleosts. Chemical lesioning of the olfactory organ with a single dose of Triton X-100 had profound effects on glomerular distribution in the olfactory bulb at 4 days after treatment, with the most significant effects in the medial region of the bulb. Glomeruli had returned by 7 days post-treatment. Analysis of the ability of the fish to detect cocktails of amino acids or bile salts consisted of counting the number of turns the fish made before and after odorant delivery. Control fish turned more after exposure to both odorants. Fish tested 4 and 7 days after chemical lesioning made more turns in response to amino acids but did not respond to bile salts. At 10 days post-lesion, these fish had regained the ability to detect bile salts. Thus, the changes seen in bulbar innervation patterns correlated to odorant-mediated behavior. We show that the adult zebrafish brain has the capacity to recover rapidly from detergent damage of the olfactory epithelium, with both glomerular distribution and odorant-mediated behavior returning in 10 days.


Placental expression of nitric oxide synthase during HELLP syndrome: the correlation with maternal-fetal Doppler velocimetry.
To correlate Doppler waveform of the uterine and umbilical vessels to placental nitric oxide synthase (NOS) expression in pregnant women with HELLP (hemolysis, elevated liver enzymes, low platelets count) syndrome. mRNA expression of inducible NOS (iNOS) and endothelial NOS (eNOS) was assessed, after cesarean section, in placental samples from 10 women affected by HELLP syndrome and 10 controls. Pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries were measured. iNOS expression was significantly lower in placenta from women with HELLP syndrome than controls. When comparing the results with Doppler flow measurements, we found a negative correlation between umbilical pulsatility index and eNOS expression (r = -0.91) and a positive correlation with iNOS expression (r = 0.86). The reduced iNOS expression in women with HELLP syndrome may indicate the extreme placental dysfunction that is unable to compensate for the endothelial derangement and related hypertension in spite of trying to improve fetoplacental perfusion and the delivery of nutrients to the fetus.


Ciguatera poisoning in French Polynesia: A review of the distribution and toxicity of Gambierdiscus spp., and related impacts on food web components and human health.
Ciguatera Poisoning (CP) is a seafood poisoning highly prevalent in French Polynesia. This illness results from the consumption of seafood contaminated with ciguatoxins (CTXs) produced by Gambierdiscus, a benthic dinoflagellate. Ciguatera significantly degrades the health and economic well-being of local communities largely dependent on reef fisheries for their subsistence. French Polynesia has been the site of rich and active CP research since the 1960's. The environmental, toxicological, and epidemiological data obtained in the frame of large-scale field surveys and a country-wide CP case reporting program conducted over the past three decades in the five island groups of French Polynesia are reviewed. Results show toxin production in Gambierdiscus in the natural environment may vary considerably at a temporal and spatial scale, and that several locales clearly represent Gambierdiscus spp. "biodiversity hotspots". Current data also suggest the "hot" species G. polynesiensis could be the primary source of CTXs in local ciguateric biotopes, pending formal confirmation. The prevalence of ciguatoxic fish and the CTX levels observed in several locales were remarkably high, with herbivores and omnivores often as toxic as carnivores. Results also confirm the strong local influence of Gambierdiscus spp. on the CTX toxin profiles characterized across multiple food web components including in CP-prone marine invertebrates. The statistics, obtained in the frame of a long-term epidemiological surveillance program established in 2007, point towards an apparent decline in the number of CP cases in French Polynesia as a whole; however, incidence rates remain dangerously high in some islands. Several of the challenges and opportunities, most notably those linked to the strong cultural ramifications of CP among local communities, that need to be considered to define effective risk management strategies are addressed.


[The research on linear control of pneumatic artificial muscles used in medical robots].
This paper presents the properties of Pneumatic artificial muscles and its application in medical robots. The linear model construction and minimum predictive error control algorithm for artificial muscles are discussed here too. This paper provides the experimental results of linear adaptive control, which show the control algorithm has certain applicable value.


Regional cerebral blood flow in delayed brain swelling following x-irradiation of the right occipital lobe in the monkey.
Four to 5 months after exposure of the right occipital lobe of the monkey to 3500 rads of X-irradiation there is a proliferative and degenerative lesion accompanied by a massive break in the blood-brain barrier. The resulting vasogenic edema causes gross swelling in the ipsilateral hemisphere, compression of the contralateral hemisphere with ventricular dilatation, and distortion of midline structures, which may result in herniation through the incisura and foramen magnum. The regional cerebral blood flow, determined by [14C]antipyrine method, at successive stages in the development and resolution of the delayed brain swelling shows a reduction of blood flow in white and gray matter, first regionally, then throughout the ipsilateral hemisphere and finally throughout the brain. This is accompanied by an increase in CSF pressure, CSF lactic dehydrogenase and total protein, and clinical signs of increased intracranial pressure. With resolution of CSF pressure, there is a return to baseline of CSF chemistry and partial resolution of the other parameters. The cerebral blood flow shows a greater recovery in gray than white matter, but there remains a diffuse depression suggesting a long-term impairment in cellular metabolism and/or blood flow regulatory mechanisms.


Association of low mechano-energetic efficiency and prognosis in liver cirrhosis.
In cirrhosis, cardiac systolic dysfunction as part of cirrhotic cardiomyopathy affects prognosis. Myocardial mechano-energetic efficiency (MEE) is an estimate of left ventricular performance. In this study we investigated the relation of MEE to patient characteristics and its impact on survival in patients with cirrhosis. We included 283 patients with cirrhosis of different severity according to the Child-Pugh classifications (A/B/C: 106/87/90). All patients had a liver vein catheterization and a hemodynamic investigation performed including determination of cardiac output (CO), stroke volume and heart rate (HR). These data were used to assess MEE, which was defined as (stroke volume/HR) × 1.666. Eighty-nine percent of patients had portal hypertension (hepatic venous pressure gradient >5 mmHg) and 80% indications of hyperdynamic circulatory state (increased CO and HR). There was no difference in MEE in Child-Pugh class C patients (2.03) versus Child-Pugh class A (1.98) and B (2.05) patients. In Child-Pugh class C patients, low MEE was associated with a poorer prognosis. In our study, MEE does not seem to be associated with severity of the liver disease, but in patients with advanced disease low MEE is associated with a poorer prognosis. The prognostic impact of MEE should be further investigated.


Factors Associated with COVID-19 Severity Among Kidney Transplant and Non-Kidney Transplant Patients at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
The COVID-19 epidemic is a rapidly shifting situation that has resulted in significant regulatory reforms and widespread initiatives to deal with the initial crisis and its effects. The COVID-19 pandemic has had a significant impact on transplantation activities. The COVID-19 pandemic has caused various important challenges in the kidney transplant industry. To identify the factors influencing COVID-19 severity in kidney transplant and non-kidney transplant patients at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. A comparative cross-sectional study was conducted. This study included 364 patients (182 kidney transplants and 182 non-kidney transplants). A systematic random sampling was used to select the respondents. Professional nurses collected data for this study using a data extraction tools. Data were analyzed by using SPSS version 25 software. A multivariable logistic regression analysis was performed to identify the association between independent variables and COVID-19 severity with adjusted odds ratio (AOR), and 95% CI for AOR and P-value for testing significance. This study included 364 patients. Off the total, 34.1% developed severe COVID-19. In Multivariable logistic regression analysis, patients with 60 years and above age groups (AOR = 4.73; 95% CI: 1.86, 12.02), aged 40-59 years (AOR = 2.70; 95% CI: 1.17, 6.22), chest congestion (AOR = 4.49; 95% CI: 2.37, 8.50), history of muscle or body aches (AOR = 0.47; 95% CI: 0.22, 0.99) shortness of breath (AOR = 3.03; 95% CI: 1.36, 6.74), changed or lost sense of taste or smell (AOR = 2.77; 95% CI: 1.34, 5.71), and muscle pain (AOR = 3.05; 95% CI: 1.40, 6.65) were significant variables associated with COVID-19 severity after adjusting for other variables. The study revealed that 34.1% of patients had severe COVID-19. The majority of these patients underwent non-kidney transplants. Age groups and symptoms, such as chest congestion, shortness of breath, changed or lost sense of taste or smell, and muscle pain, were significant predictors of COVID-19 disease severity.


Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road.
Glutamatergic transmission is widely implicated in neuropsychiatric disorders, and the discovery that ketamine elicits rapid-acting antidepressant effects by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) signaling has spurred a resurgence of interest in the field. This review explores agents in various stages of development for neuropsychiatric disorders that positively modulate AMPARs, both directly and indirectly. Despite promising preclinical research, few direct and indirect AMPAR positive modulators have progressed past early clinical development. Challenges such as low potency have created barriers to effective implementation. Nevertheless, the functional complexity of AMPARs sets them apart from other drug targets and allows for specificity in drug discovery. Additional effective treatments for neuropsychiatric disorders that work through positive AMPAR modulation may eventually be developed.


Germline BRCA mutation carriers are more likely to undergo cytoreductive surgery for relapsed, platinum sensitive, ovarian cancer.
BRCA mutations have been associated with improved outcomes in ovarian cancer patients. This study's objective was to compare the secondary cytoreduction surgery (SCS) rates among ovarian cancer patients by BRCA mutation status. The study was retrospective and included platinum sensitive recurrent high grade serous ovarian cancer patients from one Canadian center and two Israeli centers from January 1999 to December 2018. Demographic and genetic data, tumor characteristics, patterns of recurrence and surgical and medical treatments were obtained from electronic charts. Patients were grouped according to BRCA mutation status. Logistic regression analyses were used to explore potential prognostic factors of secondary cytoreduction. 147 patients were enrolled, including 97 from Canada and 50 from Israel. Forty-seven patients (32%) had a BRCA mutation, including 39 (26.5%) germline mutations and 8 (5.5%) somatic mutations. Thirty-one patients (21.1%) underwent SCS. The rate of SCS was 33.3% among the germline BRCA mutation carriers and 15.7% among patients without germline BRCA mutation (p = 0.026). Predictors of secondary cytoreduction included germline BRCA mutation (OR = 2.5, p = 0.03), time to recurrence (OR = 1.004 per month, p < 0.001), absence of lymphatic recurrence (OR = 3.08, p = 0.013), three or fewer lesions at recurrence (OR = 36.74, p < 0.001) and absence of ascites (OR = 9.1, p = 0.034). After adjusting for the number of lesions at recurrence, no other variable remained a significant predictor. Germline BRCA mutation carriers are more likely to undergo secondary cytoreduction. This may be mediated in part by lower volume disease at recurrence. This observation should be considered when planning surveillance for these patients after first-line treatment.


Atlas of transgenic Tet-Off Ca2+/calmodulin-dependent protein kinase II and prion protein promoter activity in the mouse brain.
Conditional transgenic mouse models are important tools for investigations of neurodegenerative diseases and evaluation of potential therapeutic interventions. A popular conditional transgenic system is the binary tetracycline-responsive gene (Tet-Off) system, in which the expression of the gene of interest depends on a tetracycline-regulatable transactivator (tTA) under the control of a specific promoter construct. The most frequently used Tet-Off promoter mouse lines are the Ca(2+)/calmodulin-dependent protein kinase II (CamKII) and prion protein (PrP) promoter lines, respectively. To target the regulated gene of interest to relevant brain regions, a priori knowledge about the spatial distribution of the regulated gene expression in the brain is important. Such distribution patterns can be investigated using double transgenic mice in which the promoter construct regulates a LacZ reporter gene encoding the marker β-galactosidase which can be histologically detected using its substrate X-gal. We have previously published an atlas showing the brain-wide expression mediated by the Tet-Off PrP promoter mouse line, but the distribution of activity in the Tet-Off CamKII promoter mouse line is less well known. To compare promoter activity distributions in these two Tet-Off mouse lines, we have developed an online digital atlas tailored for side-by-side comparison of histological section images. The atlas provides a comprehensive list of brain regions containing X-gal labeling and an interactive dual image viewer tool for panning and zooming of corresponding section images. Comparison of spatial expression patterns between the two lines show considerable regional and cellular differences, relevant in context of generation and analysis of inducible models based on these two tetracycline responsive promoter mouse lines.


[The effect of the spleen on tumor growth in mouse lines with various spleen sizes].
Selectively raised laboratory mice differ according to spleen size in their immunologic behavior against various tumors. A small spleen and splenectomy reduce tumor growth, whereas a large spleen or additional transfer of tumor antigen-specific spleen cells ("suppressor cells") stimulate tumor incidence.


The explanatory ability of COVID-19 life changes on quality of life: A comparison of those who have had and not had COVID-19.
The COVID-19 pandemic has undoubtedly negatively affected individuals' quality of life through multiple means such as social isolation, exacerbated mental health conditions, and financial instability. Multiple studies have demonstrated that one of the negative correlates of quality of life is the perceived danger of COVID-19 (i.e., fear of and anxiety about COVID-19). The current study addresses limitations in the literature by testing how life changes from COVID-19 explain the direct effect of the perceived danger of COVID-19 on quality of life using a United States sample between those who have had COVID-19 compared to those who have not had COVID-19. Undergraduate students (n = 196) from a Midwestern University in the United States participated in this study for course credit (White: n = 109; 55.61%; Male: n = 94; 48.0%). Participants completed this study online and at home where they responded to a demographic form and several measures of the effects of COVID-19 and quality of life. The results suggest that COVID-19 life changes fully explain the negative relationship between the perceived danger of COVID-19 and quality of life, but only in those who have had COVID-19. In the group that has never had COVID-19, the only significant relationship was the positive relationship between the perceived danger of COVID-19 on COVID-19 life changes. The results suggest that researchers may consider steering research away from the perceived danger of COVID-19 and onto remedying life changes from COVID-19 to improve individuals' quality of life. I further discuss the theoretical findings, implications, limitations, and future directions.


Comparison of hepatic and extrahepatic drug-metabolizing enzyme activities in rats given single or multiple challenge infections with Fasciola hepatica.
The activity of drug-metabolizing enzymes was compared in liver, kidneys and lungs of rats given single or repetitive fluke infections. Fascioliasis was induced by oral administration of 20 metacercariae of F. hepatica to rats, either 6, or 12 and 6, or 12, 9 and 6 weeks before sacrifice. In the liver of mono-infected rats, significant reductions (24-67%) were observed in microsomal content of cytochrome P450 and all P450-dependent monooxygenases investigated. Conjugations to glutathione or acetate were lowered by 34-50% in these animals. In multiply infected animals, a majority of specific enzymatic activities were unchanged, while some monooxygenase activities such as aminopyrine demethylation or benzo(a)pyrene hydroxylation were increased by 26-76% in the liver of tri-infected rats. A renal compensatory process occurred in all infected groups, since cytochrome P450, benzphetamine demethylation and glutathione conjugation were significantly increased. By contrast, dealkylation of benzphetamine and pentoxyresorufin were decreased in the lungs of monoinfected rats. The development of parasite resistance would account for the recovery of liver drug metabolizing capabilities in multi-infected animals.


The permeability of dental gloves following exposure to certain dental materials.
This investigation sought to study the permeability of three commonly used clinical gloves when exposed to chemical agents. A total of 35 gloves of each type were selected at random and were assigned to one of seven equally sized treatment groups. The effective barrier properties were investigated following treatment for 15 min with one of: acid etchant, Trim, cavity varnish, Hibiscrub, Hydrex and Vitremer using a dye permeability test. Following the chemical insult a 0.02% solution of erythrosine dye was introduced into each glove and the outer glove surface was washed with 10 ml of distilled water at intervals of 30, 60, 90 and 120 min. The percentage absorption of the collected washings, at 530 nm, was determined using a spectrophotometer. The results were compared with those values obtained from untreated gloves. Acid etchant and Hydrex had little effect on any of the gloves. Trim caused an increase in permeability of the vinyl gloves but had little or no effect upon those made of latex. Cavity varnish increased the permeability of both Biogel D and Tru-Touch but had no effect on Featherlite. The integrity of the latex gloves was diminished by Hibiscrub but little effect was observed in the case of the vinyl based glove. The permeability of all three gloves was increased by exposure to Vitremer liquid. Manufacturers should provide details of potential glove chemical interactions to assist dentists in glove selection.


[Prevalence of SARS-CoV-2 infection during the first wave of the pandemic among health and non-health personnel of the General Hospital of Segovia, Castilla y León].
Health and non-health workers (HNH-W) in a hospital are more exposed to SARS-CoV-2 infection than the general population. We studied the prevalence of this infection in these workers of Segovia´s Hospital after the first epidemic wave. Monocentric, observational, cross-sectional study, carried out between April 29 and May 14, 2020. The infection was diagnosed by capillary immunochromatography test for IgG and / or IgM antibodies, or PCR. Work, health, and exposure variables were studied. A total of 1,335 HNH-W participated in the study out of a total of 1,667 (80.1%), 79.3% women, with a mean age of 47.3 years, and 47.1 for men. The prevalence of infected was 21.95%, 24.7% asymptomatic. Age presented a significant OR of 1.02/year. Exposure outside of work increased the prevalence by 16.8%. The continued use of Personal Protective Equipment (PPE) and the administration of nebulizations presented an OR of 0.54 and 0.46 respectively. The symptoms associated with the highest prevalence were anosmia (OR 9.31), ageusia (OR 3.05), and fever (OR 1.94). Today, about 75% of HNH-W were infected in the first wave. The prevalence is higher among healthcare workers than the population they serve. Age is associated with a higher prevalence of infection. Almost a quarter of those infected were asymptomatic. The continuous use of PPE was associated with a lower prevalence, for that the administration of nebulisations could be safe. The symptoms with the greatest association were fever, anosmia, and ageusia.


Clinical Impact of Deep Brain Stimulation on the Autonomic System in Patients with Parkinson's Disease.
The role of deep brain stimulation (DBS) in the management of motor symptoms in patients with Parkinson's disease is well defined. However, it is becoming increasingly clear that DBS can either improve or worsen a number of non-motor phenomena. We examined the published literature to better understand the effects on autonomic symptoms following DBS of the subthalamic nucleus and the globus pallidus interna. We conducted a PubMed search of studies regarding the effects of DBS on the autonomic system published from January 2001. We searched for the following terms and their combinations: Parkinson's disease, deep brain stimulation, subthalamic nucleus, globus pallidus interna, autonomic dysfunction. Most studies reported in the literature focus on DBS targeting the subthalamic nucleus, with particular emphasis on favorable outcomes regarding gastrointestinal function and bladder control. However, the emergence or worsening of autonomic symptoms in subgroups of patients has also been documented. More controversial is the effect of stimulation on the cardiovascular, pulmonary, and thermo-regulatory systems as well as sexual functioning. Data regarding the influence of DBS on the autonomic system when the target is the globus pallidus interna is less forthcoming, with target selection varying according to centre and clinical indication. DBS appears to affect the autonomic nervous system, with varying degrees of influence, which may or may not be clinically beneficial for the patient. A better understanding of these effects could help personalize stimulation for individual patients with autonomic disorders and/or avoid autonomic symptoms in susceptible patients.


An energy and time prediction model for remanufacturing process using graphical evaluation and review technique (GERT) with multivariant uncertainties.
The rising energy price and stringent energy efficiency-related legislations encourage decision makers to concern more about energy efficiency in current manufacturing competition. In this regard, a quick and accurate prediction of the energy consumption and makespan in the manufacturing process has been a prerequisite for energy optimization. Given the various types of uncertainties in the remanufacturing system such as stochastic, fuzzy, and grey factors, the present study developed a prediction model that forecasts the energy consumption, completion time, and probability of processing routes. It adopted the graphical evaluation and review technique (GERT) to convert remanufacturing process into an uncertain network, considering multivariant uncertainties instead of merely stochastic uncertainty in prior works. We provided a generic seven steps to implement this approach. The energy consumption and completion time of remanufacturing process were determined in conjunction with Mason's rule and chance-constrained programming. Connecting rod reprocessing was presented as a numerical example. Based on the GERT network, we conducted an Arena simulation to validate the feasibility and effectiveness of this approach. In addition, we adopted the concept of criticality index to conduct sensitivity analysis and examine the predominant factors affecting the concerned indicators. This study would enable remanufacturers to perform a quick prediction of energy use and makespan in remanufacturing process.


Docosahexaenoic acid promotes neuronal differentiation by regulating basic helix-loop-helix transcription factors and cell cycle in neural stem cells.
Recent studies have suggested that docosahexaenoic acid (DHA) enhances neuronal differentiation of neural stem cells (NSCs) isolated from rat embryonic day 14.5. However the underlying mechanism remains largely unknown. One hypothesis supported by DHA controls the expression level of basic helix-loop-helix (bHLH) transcription factors, such as hairy and enhancer of split 1 (Hes1), Mash1, neurogenin1, and NeuroD; another is that previous studies in retinal progenitor cells DHA affects the cell cycle. In this study, we show that treatment with DHA under differentiation conditions without basic fibroblast growth factor, (1) increases Tuj-1 and MAP2 positive cells in NSCs, (2) that the expression level of Hes1 mRNA and protein decreased significantly from day 1 to day 4, on the other hand, the NeuroD mRNA expression level increased from day 1 to day 4 after treatment with DHA and (3) decreased the percentage of S-phase cells, which correlated with prolonged expression of cyclin-dependent kinase inhibitor p27(kip1), suggesting that DHA enhances neuronal differentiation of NSCs, in part, by controlling the bHLH transcription factors and promoting cell cycle exit. We therefore speculate that DHA is one of the essential key molecules for neuronal differentiation of NSCs.


Extreme biomimetics: Preservation of molecular detail in centimeter-scale samples of biological meshes laid down by sponges.
Fabrication of biomimetic materials and scaffolds is usually a micro- or even nanoscale process; however, most testing and all manufacturing require larger-scale synthesis of nanoscale features. Here, we propose the utilization of naturally prefabricated three-dimensional (3D) spongin scaffolds that preserve molecular detail across centimeter-scale samples. The fine-scale structure of this collagenous resource is stable at temperatures of up to 1200°C and can produce up to 4 × 10-cm-large 3D microfibrous and nanoporous turbostratic graphite. Our findings highlight the fact that this turbostratic graphite is exceptional at preserving the nanostructural features typical for triple-helix collagen. The resulting carbon sponge resembles the shape and unique microarchitecture of the original spongin scaffold. Copper electroplating of the obtained composite leads to a hybrid material with excellent catalytic performance with respect to the reduction of p-nitrophenol in both freshwater and marine environments.


CNS tumor with EP300::BCOR fusion: discussing its prevalence in adult population.
The Central Nervous System (CNS) tumor with BCOR internal tandem duplication (ITD) has recently been added as a novel embryonal histomolecular tumor type to the 2021 World Health Organization (WHO) Classification of CNS Tumors. In addition, other CNS tumors harboring a BCOR/BCORL1 fusion, which are defined by a distinct DNA-methylation profile, have been recently identified in the literature but clinical, radiological and histopathological data remain scarce. Herein, we present two adult cases of CNS tumors with EP300::BCOR fusion. These two cases presented radiological, histopathological, and immunohistochemical homologies with CNS tumors having BCOR ITD in children. To compare these tumors with different BCOR alterations, we performed a literature review with a meta-analysis. CNS tumors with EP300::BCOR fusion seem to be distinct from their BCOR ITD counterparts in terms of age, location, progression-free survival, tumor growth pattern, and immunopositivity for the BCOR protein. CNS tumors from the EP300::BCOR fusion methylation class in adults may be added to the future WHO classification.


The effects of adjuvant chemotherapy on bone density in postmenopausal women with early breast cancer.
Adjuvant chemotherapy for breast cancer can have adverse effects on bone. We investigated the effects of adjuvant chemotherapy on bone mineral density in postmenopausal women with early-stage breast cancer. We performed a chart review of all our breast center patients who had spine or hip bone density measured by dual-energy X-ray absorptiometry at our institution after treatment for stage I or II breast cancer. Patients who had other causes of metabolic bone disease were excluded. Multivariate regression analysis was used to adjust for confounding factors. Results were expressed as age-adjusted standard deviation units (Z scores). Of the 130 eligible women, 36 (28%) received adjuvant chemotherapy and 94 (72%) did not. Mean adjusted bone density scores in both the hip (0.65 SD units; 95% confidence interval [CI]: 0.32 to 0.98 SD units; P = 0.0002) and spine (0.60 SD units; 95% CI: 0.01 to 1.19 SD units; P = 0.05) were significantly lower in patients who had received adjuvant chemotherapy compared with those who had not. Women who were postmenopausal when they developed breast cancer and who received adjuvant chemotherapy had lower bone density than those who did not. Whether this effect is caused by adjuvant chemotherapy remains to be determined.


Use of histone methyltransferase inhibitors in cancer treatment: A systematic review.
Histone modifications are an epigenetic mechanism, and the dysregulation of these proteins is known to be associated with the initiation and progression of cancer. In the search for the development of new and more effective drugs, histone modifications were identified as possible therapeutic targets. Histone methyltransferase (HMT) inhibitors correspond to the third generation of epigenetic drugs capable of writing or deleting epigenetic information. This systematic review summarized the development and prospect for the use of different HMT inhibitors in cancer therapy. An electronic search was applied across CENTRAL, Clinical Trials, Embase, LILACS, LIVIVO, Open Gray, PubMed, Scopus, and Web of Science. Based on the title and abstracts, two authors independently selected eligible studies. After the complete reading of the articles, based on the eligibility criteria, 11 studies were included in the review. Different inhibitors of HMT have been explored in multiple clinical studies, and have shown considerable anti-tumor effects. However, few phase 2 studies have been completed and/or have available results. The most advanced clinical trials mainly include tazemetostat, an Enhancer of zeste homolog 2 (EZH2) inhibitor approved for follicular lymphoma (FL). The use of HMT inhibitors has presented, so far, concise results in the treatment of hematological cancers, moreover, the adverse effects presented after the use of these medicines (alone or in combination) did not show a high level of risk for the patient. These findings, in addition to ongoing clinical studies, can represent a promising future regarding the use of HMT inhibitors in treating different types of cancer.


Cardiac Point-of-Care Ultrasound and Multi-Disciplinary Improvement Opportunities in Acute Systolic Heart Failure Management in a Pediatric Emergency Center.
Cardiac point-of-care ultrasound (POCUS) has the ability to rapidly assess function and identify systolic heart failure (HF), an often-missed diagnosis. POCUS has the potential to expedite medical intervention, improving overall outcomes. There have been limited studies describing pediatric emergency center (EC) utilization of cardiac POCUS and its impact on outcomes in pediatric patients. Authors performed a retrospective chart review at a tertiary children's hospital to identify all patients admitted from the EC to the Cardiac Intensive Care Unit (CICU) with acute systolic HF between January 2017 and August 2019. Outcome measures included EC length of stay (LOS), CICU LOS, and time until first IV HF medicine was administered. A total of 21 patients and 24 encounters meeting criteria were identified. Cardiac POCUS agreed with standard echocardiography in 8 of 9 cases. Patients who had a cardiac POCUS in the EC seemed more likely to receive their first dose of intravenous heart failure medication while in the Emergency Center (70% vs 43%). There was a trend toward significance, but it did not reach statistical significance (p = 0.1). EC and CICU LOS were not significantly different between POCUS and non-POCUS groups. Cardiac POCUS has the potential to have a valuable role in the early diagnosis of acute systolic HF in children. However, early diagnosis by POCUS did not translate into shorter EC or CICU LOS. This pilot data serves as a baseline for efforts to promote earlier clinical recognition of acute HF and more efficient collaboration between clinical services.


A postgraduation follow-up of social work students trained in "SBIRT": Rates of usage and perceptions of effectiveness.
Screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based modality that can help social workers work with substance-using clients as part of an integrated health care approach. This study reports the findings of a post-graduation one-year follow-up survey of 193 master's and bachelor's social work students trained in SBIRT in practice courses at a Northeast urban college. Forty-three percent of the trainees who were practicing social work after graduation were using SBIRT. A content analysis of participants' comments found that the vast majority found SBIRT to be a valuable practice modality, with barriers to utilization of SBIRT identified.


Operational and structural A-stage improvements for high-rate carbon removal.
Biosorption of organics is investigated at two sites in order to optimize operation and infrastructure for carbon removal and redirection in upstream, high-rate processes. Sufficient process temperature and stable mixed liquor solids concentration were established as the key impact parameters for the process performance. Improved COD removal was achieved by either substantially enhanced aeration (elevated metabolic state) or by enhanced flocculation capability (dosed chemicals). Separation and thickening of organics are typically operated as continuous-flow processes. The optimization of performance parameters led to a new A-stage process named alternating activated adsorption. The AAA process is presented as a novel configuration linking biosorption and thickening capabilities in an alternating scheme without mechanical equipment. The performance data from its first trial indicate benefits from process dynamics including high organics capture rates and thickening capabilities reaching solid concentrations higher than 40 g(TSS)/L. COD removal could be increased further by adding biologically generated polymer, that is waste sludge from B-stage. © 2020 Water Environment Federation PRACTITIONERS POINTS: Enhanced preliminary treatment helps to increase capacity and energy efficiency. Low RAS rates, SRT control, aeration, high temperatures, and metal dosing are key performance parameters for removal rates and energy efficiency. The Triple-A process offers new possibilities for A-stage in terms of performance increase and flexibility showing similar or better results compared with conventional A-stage. Adding B-sludge improved COD and nutrient removal rates. High preliminary removal rates of COD and N foster sidestream processes.


Regular immunohistochemical localization of endothelin-1 and endothelin-B receptor in normal, hyperplastic and neoplastic human adrenocortical cells.
The localization of endothelin (ET)-1/big ET-1, ET-3/big ET-3, ET-A and ET-B receptor was immunohistochemically examined in human adrenal glands composed of 36 normal cases, nine hyperplasia, 70 adenomas and seven carcinomas of cortical cells. In normal adrenals, ET-1/big ET-1 and ET-B receptor were regularly detected in the cortical cells, especially in the zona fasciculata for ET-1 and zona glomerulosa for ET-B receptor but not in the medulla, while ET-A receptor localized occasionally in endothelial cells or rarely in cortical cells and ET-3/big ET-3 was very limited in the cortical cells. In hyperplasia, adenoma and carcinoma, ET-1/big ET-1 and ET-B receptor showed frequent localization, although focal distribution of the ET-B receptor was rather predominant in these groups. ET-A receptor and ET-3/big ET-3 were very infrequently expressed. Functioning versus non-functioning and hypertensive versus normotensive cases revealed no significant differences in the frequency of positive cells for ET-1/big ET-1, ET-3/big ET-3, ET-A receptor or ET-B receptor. Alternatively, the frequency of immunoreactivity to ET-1/big ET-1 or ET-B receptor significantly decreased in hyperplasia, adenoma and carcinoma, when compared with that of normal adrenal cortex. The present study, therefore, indicates that ET-1/big ET-1 and ET-B receptor are a prevalent ligand-receptor system in normal and hyperplastic/neoplastic adrenocortical cells, even with a malignant profile, and may contribute in maintaining adrenocortical cell function or cell viability but not cell growth or systemic hypertension.


Effects of dietary resveratrol supplementation on the chemical composition, oxidative stability and meat quality of ducks (Anas platyrhynchos).
The effects of dietary resveratrol (0, 300, 400 and 500 mg/kg) on the chemical composition, antioxidative capacity, meat quality and volatile compound concentrations of duck meat were investigated. The results showed that dietary resveratrol had no significant effects on the chemical composition. Dietary resveratrol supplementation increased superoxide dismutase, glutathione peroxidase, catalase activity, pH15 min, pH24 h and color, and reduced the malondialdehyde, and carbonyl contents and shear force, thereby improving water mobility and distribution (T2b, T21, T22), drip loss, cooking loss and volatile compounds concentration of duck meat. In conclusion, dietary resveratrol supplementation improved the meat quality of ducks by enhancing the antioxidant capacity, improving the color and shear force, and suppressing lipid and protein oxidation, and 500 mg/kg dietary resveratrol had the greatest effect in this study.


Investigating the emergence of sex differences in jealousy responses in a large community sample from an evolutionary perspective.
Sex differences in jealousy responses to sexual and emotional infidelity are robust in samples of heterosexual adults, especially in more gender egalitarian nations. However, investigations of when and how these differences develop have been scant. We applied two forced choice infidelity scenarios in a large community sample of high school students (age 16-19, N = 1266). In line with previous findings on adults using the forced choice paradigm, adolescent males found the sexual aspect of imagined infidelity more distressing than adolescent females did. Nevertheless, there was no effect of age on the jealousy responses, and age did not moderate the sex difference. There were neither any effects of three covariates (having had first sexual intercourse, being in a committed romantic relationship, and sociosexuality), neither as markers of pubertal maturation nor as psychosocial environmental stimuli. Future research needs to investigate even younger samples in order to specify at what age the sex difference in jealousy responses emerges.


Examining the role that weight perception and social influences have on mental health among youth in the COMPASS study.
We investigated whether social health mitigates the association between weight perception and anxiety and depression 1 year later in a large sample of Canadian youth in a prospective, gender-specific analysis. We used 2 years of linked survey data from 20,485 grade 9-11 students who participated in wave 6 (2017/18) and 7 (2018/19) of the COMPASS study. Mental health outcomes included the Generalized Anxiety Disorder-7 item (GAD-7) scale and the 10-item Centre for Epidemiological Studies Depression Scale Revised (CESD-10-R). Social health encompassed students' perceived relationships with friends, family, teachers, and within schools. Multilevel, prospective, linear models regressed mental health (at wave 7) on social health (at wave 6) and weight perception (at wave 6) while controlling for weight status, ethnicity, and grade (at wave 6). Interaction terms were used to test social health factors as moderators in the association between weight perception and mental health. Overweight perceptions were associated with higher anxiety and depression scores among youth; this was more pronounced among females. Social health was associated with lower anxiety and depression scores. Among females only, an overweight perception had the highest predicted scores for significant depressive symptoms. Among males only, underweight perceptions were associated with higher anxiety scores. No social health factors had moderating effects in females, and only two interactions were significant among males: feeling safe at school had protective associations with anxiety scores among those with underweight perceptions while those with overweight perceptions had higher depression scores when they reported rewarding social relationships. Overweight perceptions in all youth, and underweight perceptions in males, predicted anxiety and depression symptoms 1 year later. The role of social health should not be discounted as a means of preventing anxiety and depression in youth, although this study suggests it is not sufficient to protect against adverse associations with overweight perceptions for all youth, and underweight perceptions for males.


Reliability, validity, and maturation-related differences of frontal and sagittal plane landing kinematic measures during drop jump and tuck jump screening tests in male youth soccer players.
To determine the inter-rater and intra-rater reliability of frontal and sagittal plane landing kinematic measures during drop jump (DVJ) and tuck jump (TJA) tasks in male youth soccer players, to assess the concurrent validity between DVJ and TJA tests, and to evaluate the ability of both tasks to detect differences between players' stage of maturation. Cross-sectional study. 223 male youth soccer players. Frontal plane knee projection angles (FPPA), and hip (HF), knee (KF) and ankle (AF) flexion angles at initial contact (IC) and peak flexion (PF) (i.e., the deepest landing position) in the sagittal plane were assessed. Good-to-excellent inter- and intra-rater reliability (ICC > 0.75; TEMST < 0.3; CVTE < 5%) for the FPPA, HF and KF during DVJ and TJA tasks were found. A low concurrent validity between DVJ and TJA measures was reported. Differences by maturity status (BF10 > 10; error < 10; δ > 0.6) were only identified for the TJA. Pre-PHV group reported higher FPPA, HF-IC, HF-PF, and KF-IC values, as well as lower AF-IC than post-PHV. Pre-PHV also displayed greater HF-IC and KF-IC than circa-PHV group. Although both tests are reliable, the TJA might be viewed as a more informative tool given it shows greater FPPA and can also detect differences by maturity status.


Identification of new reference genes with stable expression patterns for gene expression studies using human cancer and normal cell lines.
Reverse transcription-quantitative real-time PCR (RT-qPCR) is a ubiquitously used method in biological research, however, finding appropriate reference genes for normalization is challenging. We aimed to identify genes characterized with low expression variability among human cancer and normal cell lines. For this purpose, we investigated the expression of 12 candidate reference genes in 13 widely used human cancer cell lines (HeLa, MCF-7, A-549, K-562, HL-60(TB), HT-29, MDA-MB-231, HCT 116, U-937, SH-SY5Y, U-251MG, MOLT-4 and RPMI-8226) and, in addition, 7 normal cell lines (HEK293, MRC-5, HUVEC/TERT2, HMEC, HFF-1, HUES 9, XCL-1). In our set of genes, we included SNW1 and CNOT4 as novel candidate reference genes based on the RNA HPA cell line gene data from The Human Protein Atlas. HNRNPL and PCBP1 were also included along with the "classical" reference genes ACTB, GAPDH, IPO8, PPIA, PUM1, RPL30, TBP and UBC. Results were evaluated using GeNorm, NormFiner, BestKeeper and the Comparative ΔCt methods. In conclusion, we propose IPO8, PUM1, HNRNPL, SNW1 and CNOT4 as stable reference genes for comparing gene expression between different cell lines. CNOT4 was also the most stable gene upon serum starvation.


On monitoring the multiply malformed infant. I: Case-finding, case-recording, and data handling in a Latin American program.
The methods used by the Latin American Collaborative Study of Congenital Malformations (ECLAMC) for monitoring the birth prevalence of multiply malformed infants are based on a clinical-epidemiological approach oriented to the early detection of teratogenic agents. They consist of three steps: 1) the analysis of observed vs expected rates of all congenital anomalies (CA), including their isolated and associated forms; 2) the same type of analysis applied to each multiple congenital anomaly (MCA) pattern; and 3) a clinical case presentation reserved only for those considered as true MCA because of presence of three or more independent CA. During the period 1982-1983 299,231 infants were examined. Multiply malformed infants, excluding Down syndrome cases, were born at a rate of 4/10,000, 40% having syndromes (two or more interrelated CA), 30% anomaly pairs, ie, two independent CA, and 30% true MCA cases. In a program with 150,000 births per year, as in ECLAMC, this means about five true MCA cases per week, a number easily handled individually on a clinical basis.


The interindividual variability of multimodal brain connectivity maintains spatial heterogeneity and relates to tissue microstructure.
Humans differ from each other in a wide range of biometrics, but to what extent brain connectivity varies between individuals remains largely unknown. By combining diffusion-weighted imaging (DWI) and magnetoencephalography (MEG), this study characterizes the inter-subject variability (ISV) of multimodal brain connectivity. Structural connectivity is characterized by higher ISV in association cortices including the core multiple-demand network and lower ISV in the sensorimotor cortex. MEG ISV exhibits frequency-dependent signatures, and the extent of MEG ISV is consistent with that of structural connectivity ISV in selective macroscopic cortical clusters. Across the cortex, the ISVs of structural connectivity and beta-band MEG functional connectivity are negatively associated with cortical myelin content indexed by the quantitative T1 relaxation rate measured by high-resolution 7 T MRI. Furthermore, MEG ISV from alpha to gamma bands relates to the hindrance and restriction of the white-matter tissue estimated by DWI microstructural models. Our findings depict the inter-relationship between the ISV of brain connectivity from multiple modalities, and highlight the role of tissue microstructure underpinning the ISV.


Efficacy of thrombolysis in younger and older adult patients suffering their first acute q-wave myocardial infarction.
Advancing age is an independent predictor of increased mortality after acute myocardial infarction (AMI). Several hypotheses have been developed to try to explain this phenomenon, but data available about the efficacy of thrombolytic therapy in older patients are still not conclusive. The goal of this study was to investigate the efficacy of thrombolysis in adult and older patients who suffered their first AMI. Retrospective cohort study. A coronary care unit. The sample included 244 younger (aged <65, n = 166) and older (age 65, n = 78) adult patients suffering their first Q-wave AMI, all receiving thrombolysis with human-recombinant tissue-type plasmin-ogen activator (100 mg total dose within 2.5 hours of the onset of AMI. Infarct size was estimated by isoenzyme creatine kinase-myoglobin (CK-MB) release, measuring the area under the curve as a function of time. ST elevation, the sum of ST elevation above the baseline, and the sum of R wave height in precordial leads V1-V6 were evaluated using 12-lead electrocardiograms. Myocardial reperfusion was calculated when ST-segment elevation decreased more than 60 with respect to the most abnormal peak detected. CK-MB peak level was significantly smaller in younger patients than in older ones (P< .01) and was significantly correlated with increasing age (P< .0001). Area under the 36-hour CK-MB curve was lower in younger patients than in older ones (P< .0001) and was well correlated with increasing age (P< .01). Reperfusion time was significantly shorter in younger patients (P< .05), and age was significantly correlated with reperfusion time (P< .001). Infarct size was greater and reperfusion time was longer in older patients than in younger ones with first Q-wave AMI treated with thrombolysis. Infarct size and reperfusion time were linearly correlated with increasing age. These findings may help explain the increase in mortality due to AMI observed with advancing age.


Hyperspectral determination of eutrophication for a water supply source via genetic algorithm-partial least squares (GA-PLS) modeling.
Morse Reservoir (MR), a major source of the water supply for the Indianapolis metropolitan region, is now experiencing nuisance cyanobacterial blooms. These blooms cause water quality degradation, as well as reducing the aesthetic quality of water by producing toxins, scums, and foul odors. Hyperspectral remote sensing data from both in situ and airborne AISA measurements were applied to GA-PLS by relating the spectral signal with measured water eutrophication parameters, e.g., chlorophyll-a (Chl-a), phycocyanin (PC), total suspended matter (TSM), and Secchi disk depth (SDD). Our results indicate that GA-PLS relating field sensor acquired spectral reflectance to the above-mentioned four parameters yielded low root mean square error between measured and estimated Chl-a (RMSE=10.4; Range (R): 1.8-215.8 μg/L), PC (RMSE=18.6; R: 1.4-371.0 μg/L), TSM (RMSE=3.8; R: 3.6-81.4 mg/L), SDD (RMSE=5.8; R: 25-135 cm) for MR. The GA-PLS model also yielded high performance with AISA image spectra, and the RMSEs were 12.1 μg/L, 25.3 μg/L, 5.9 mg/L and 5.7 cm, respectively for Chl-a, PC, TSM, and SDD. Four water quality parameters were mapped with GA-PLS using AISA hyperspectral image. Based on these results, in situ and airborne hyperspectral remote sensors can provide both quantitative and qualitative information on the distribution and concentration of cyanobacteria, suspended matter, and transparency in MR.


Does deidentification of data from wearable devices give us a false sense of security? A systematic review.
Wearable devices have made it easier to generate and share data collected on individuals. This systematic review seeks to investigate whether deidentifying data from wearable devices is sufficient to protect the privacy of individuals in datasets. We searched Web of Science, IEEE Xplore Digital Library, PubMed, Scopus, and the ACM Digital Library on Dec 6, 2021 (PROSPERO registration number CRD42022312922). We also performed manual searches in journals of interest until April 12, 2022. Although our search strategy had no language restrictions, all retrieved studies were in English. We included studies showing reidentification, identification, or authentication with data from wearable devices. Our search retrieved 17 625 studies, and 72 studies met our inclusion criteria. We designed a custom assessment tool for study quality and risk of bias assessments. 64 studies were classified as high quality and eight as moderate quality, and we did not detect any bias in any of the included studies. Correct identification rates were typically 86-100%, indicating a high risk of reidentification. Additionally, as little as 1-300 s of recording were required to enable reidentification from sensors that are generally not thought to generate identifiable information, such as electrocardiograms. These findings call for concerted efforts to rethink methods for data sharing to promote advances in research innovation while preventing the loss of individual privacy.


Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine-Arginine-Rich Protein ASF/SF2.
Positive transcription elongation factor-b (P-TEFb) is required for the release of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for efficient proceeding to the transcription elongation. It consists of two core subunits-CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is the major and most studied combination. We have previously identified a novel splice variant of cyclin T1, cyclin T1b, which negatively regulates the transcription elongation of HIV-1 genes as well as several host genes. In this study, we revealed the serine-arginine-rich protein, ASF/SF2, as a regulatory factor of the alternative splicing of cyclin T1 gene. ASF/SF2 promotes the production of cyclin T1b versus cyclin T1a and regulates the expression of cyclin T1-depedent genes at the transcription level. We further found that a cis-element on exon 8 is responsible for the skipping of exon 7 mediated by ASF/SF2. Collectively, ASF/SF2 is identified as a splicing regulator of cyclin T1, which contributes to the control of the subsequent transcription events. J. Cell. Biochem. 118: 4020-4032, 2017. © 2017 Wiley Periodicals, Inc.