Multi-wavelength quantitative differential phase contrast imaging by radially asymmetric illumination.
A new approach for achieving isotropic differential phase contrast imaging by applying multi-wavelength asymmetric illumination is demonstrated. Multi-wavelength isotropic differential phase contrast scheme (MW-iDPC) can be implemented using an add-on module in any commercial inverted microscope. Isotropy of intensity transfer function is achieved using three axis measurements. The expression for MW-iDPC imaging is presented, and detailed mathematical analysis is performed for transfer function. By applying color leakage correction, image sensor responses can be calibrated. Asymmetric illumination masks are designed, and simulation studies for intensity of the transfer function are performed. We utilize the MW-iDPC system to reconstruct quantitative phase images of standard microspheres and live breast cancer cells. The optical thickness of cells can be measured with high accuracy and image acquisition time is reduced significantly.


The Dyspnoea, Obstruction, Smoking, Exacerbation (DOSE) index is predictive of mortality in COPD.
The Dyspnoea, Obstruction, Smoking, Exacerbation (DOSE) index was designed to assess disease severity and for the clinical management of chronic obstructive pulmonary disease (COPD), but has not been evaluated as a prognostic instrument for mortality in a population including primary care patients. The aim of this study was to investigate the associations of the DOSE index with mortality in primary and secondary care COPD patients. Information was collected from 1,111 COPD patients aged 34-75 years randomly selected from 70 Swedish primary and secondary care centres. Data were obtained using patient questionnaires and record review and the Swedish Board of Health and Welfare provided mortality data. The study population included 562 patients with data on all DOSE index components. The DOSE index was calculated using the MRC dyspnoea scale, forced expiratory volume in 1 second (FEV₁) as percentage of predicted (FEV₁%pred), smoking status, and exacerbation rate. The exacerbation rate over 6 months prior to record review was used to estimate the annual rate. Cox regression analyses estimated survival with adjustment for age, sex, and heart disease. Over 5 years, 116 patients (20.6%) died. Mortality was higher in patients with DOSE index ≥4 (42.4%) than for lower scores (11.0%) (p<0.0001). Compared with a DOSE index score of 0-3, the hazard ratio for mortality was 3.48 (95% CI 2.32 to 5.22) for a score of 4-5, and was 8.00 (95% CI 4.67 to 13.7) for a score of 6-7. The DOSE index is associated with mortality in COPD patients in primary and secondary care and can be used to assess prognosis in addition to other clinically relevant issues.


Whole-Brain Image Analysis and Anatomical Atlas 3D Generation Using MagellanMapper.
MagellanMapper is a software suite designed for visual inspection and end-to-end automated processing of large-volume, 3D brain imaging datasets in a memory-efficient manner. The rapidly growing number of large-volume, high-resolution datasets necessitates visualization of raw data at both macro- and microscopic levels to assess the quality of data, as well as automated processing to quantify data in an unbiased manner for comparison across a large number of samples. To facilitate these analyses, MagellanMapper provides both a graphical user interface for manual inspection and a command-line interface for automated image processing. At the macroscopic level, the graphical interface allows researchers to view full volumetric images simultaneously in each dimension and to annotate anatomical label placements. At the microscopic level, researchers can inspect regions of interest at high resolution to build ground truth data of cellular locations such as nuclei positions. Using the command-line interface, researchers can automate cell detection across volumetric images, refine anatomical atlas labels to fit underlying histology, register these atlases to sample images, and perform statistical analyses by anatomical region. MagellanMapper leverages established open-source computer vision libraries and is itself open source and freely available for download and extension. © 2020 Wiley Periodicals LLC. Basic Protocol 1: MagellanMapper installation Alternate Protocol: Alternative methods for MagellanMapper installation Basic Protocol 2: Import image files into MagellanMapper Basic Protocol 3: Region of interest visualization and annotation Basic Protocol 4: Explore an atlas along all three dimensions and register to a sample brain Basic Protocol 5: Automated 3D anatomical atlas construction Basic Protocol 6: Whole-tissue cell detection and quantification by anatomical label Support Protocol: Import a tiled microscopy image in proprietary format into MagellanMapper.


Development of a challenge assessment tool for high-functioning children with an acquired brain injury.
To develop a performance-based challenge assessment to evaluate gross motor abilities of high-functioning youth with an acquired brain injury (ABI). Potential items were identified from the literature. A panel of 4 expert physical therapists selected items on the basis of 3 criteria: safety to test, feasibility to administer, and importance to perform. Item reduction was completed using ratings from a physical therapist web survey. The Acquired Brain Injury-Challenge Assessment (ABI-CA) was created and pilot tested with youth with an ABI. Seventy-eight items were identified and reduced to 47 items following expert panel discussion. Web-survey item reduction by 75 pediatric physical therapists yielded a 24-item ABI-CA that was administered to 6 youth with an ABI, aged 8 to 17 years. The ABI-CA mean score was 50.7/81.0 (SD = 17.4). The ABI-CA was feasible to administer and demonstrated gross motor activity challenges beyond the Gross Motor Function Measure. Response option refinement and measure validation are required prior to clinical/research use.


KRAB zinc finger proteins.
Krüppel-associated box domain zinc finger proteins (KRAB-ZFPs) are the largest family of transcriptional regulators in higher vertebrates. Characterized by an N-terminal KRAB domain and a C-terminal array of DNA-binding zinc fingers, they participate, together with their co-factor KAP1 (also known as TRIM28), in repression of sequences derived from transposable elements (TEs). Until recently, KRAB-ZFP/KAP1-mediated repression of TEs was thought to lead to irreversible silencing, and the evolutionary selection of KRAB-ZFPs was considered to be just the host component of an arms race against TEs. However, recent advances indicate that KRAB-ZFPs and their TE targets also partner up to establish species-specific regulatory networks. Here, we provide an overview of the KRAB-ZFP gene family, highlighting how its evolutionary history is linked to that of TEs, and how KRAB-ZFPs influence multiple aspects of development and physiology.


Occupational physical activities and osteoarthritis of the knee.
To assess the risk of knee osteoarthritis (OA) associated with kneeling, squatting, and other occupational activities. We compared 518 patients who were listed for surgical treatment of knee OA and an equal number of control subjects from the same communities who were matched for sex and age. Histories of knee injury and occupational activities were ascertained at interview, height and weight were measured, and the hands were examined for Heberden's nodes. Data were analyzed by conditional logistic regression. After adjustment for body mass index (BMI), history of knee injury, and the presence of Heberden's nodes, risk was elevated in subjects who reported prolonged kneeling or squatting (odds ratio [OR] 1.9; 95% confidence interval [95% CI] 1.3-2.8), walking >2 miles/day (OR 1.9; 95% CI 1.4-2.8), and regularly lifting weights of at least 25 kg (OR 1.7; 95% CI 1.2-2.6) in the course of their work. The risks associated with kneeling and squatting were higher in subjects who also reported occupational lifting, and appeared to interact multiplicatively with the risk conferred by obesity. People with a BMI of > or =30 kg/m2 whose work had entailed prolonged kneeling or squatting had an OR of 14.7 (95% CI 7.2-30.2), compared with subjects with a BMI <25 kg/m2 who were not exposed to occupational kneeling or squatting. There is now strong evidence for an occupational hazard of knee OA resulting from prolonged kneeling and squatting. One approach to reducing this risk may lie in the avoidance of obesity in people who perform this sort of work.


Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction.
Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR.


SNT1/FRS2 mediates germinal vesicle breakdown induced by an activated FGF receptor1 in Xenopus oocytes.
The docking protein SNT1/FRS2 (fibroblast growth factor receptor substrate 2) is implicated in the transmission of extracellular signals from the fibroblast growth factor receptor (FGFR), which plays vital roles during embryogenesis. Activating FGFR mutations cause several craniosynostoses and dwarfism syndromes in humans. Here we show that the Xenopus homolog of mammalian FRS-2 (XFRS2) is essential for the induction of oocyte maturation by an XFGFR1 harboring an activating mutation (XFGFR1act). Using a dominant-negative form of kinase suppressor of Ras, we show the Mek activity is required for germinal vesicle breakdown (GVBD) induced by co-expression of XFGFR1act and XFRS2, but this activity is not required for progesterone-induced GVBD. Furthermore, Mek/MAPK activity is critical for the induction and/or maintenance of H1 kinase activity at metaphase of meiosis II in progesterone-treated oocytes. An activated XFGFR1 containing a mutation in the phospholipase Cgamma binding site (XFGFR1actY672F) displayed a reduced ability to induce cell-cycle progression in oocytes, suggesting phospholipase Cgamma may not be necessary but that it augments XFGFR signaling in this system. Oocytes co-expressing XFGFR1act and XFRS2 showed substantial H1 kinase activity, but this activity was blocked when the oocytes were treated with the phosphatidylinositol 3-kinase inhibitor LY294002. Although phosphatidylinositol 3-kinase activity is essential for XFGFR1act/XFRS2-induced oocyte maturation, this activity is not required for maturation induced by progesterone. Finally, ectopic expression of Xspry2, a negative regulator of XFGFR signaling, greatly reduced MAPK activation and GVBD induced by the expression of either XFGFR1act plus XFRS2 or activated Ras (H-RasV12). In contrast, Xspry2 did not prevent GVBD induced by an activated form of Raf1, suggesting that Xspry2 exerts its inhibitory function upstream or parallel to Raf and downstream of Ras.


Infantile perianal pyramidal protrusion.
The number of reported cases of infantile perianal eruption has been increasing. However, infantile pyramidal protrusion located in the midline anterior to the anus has apparently been reported mainly as acrochordons or skinfolds. Fifteen infants (14 girls and 1 boy) had a pyramidal protrusion located only in the midline anterior to the anus. Histological examination revealed acanthosis in the epidermis, marked edema in the upper dermis, and mild infiltrates in the dermis. The patients had been brought to the hospital because of swelling of the protrusion. However, all protrusions showed reduction without any treatment. Infantile pyramidal protrusion located only in the midline anterior to the anus should be distinguished from acrochordons or skinfolds based on the characteristic clinical features.


Modeling a measurement-device-independent quantum key distribution system.
We present a detailed description of a widely applicable mathematical model for quantum key distribution (QKD) systems implementing the measurement-device-independent (MDI) protocol. The model is tested by comparing its predictions with data taken using a proof-of-principle, time-bin qubit-based QKD system in a secure laboratory environment (i.e. in a setting in which eavesdropping can be excluded). The good agreement between the predictions and the experimental data allows the model to be used to optimize mean photon numbers per attenuated laser pulse, which are used to encode quantum bits. This in turn allows optimization of secret key rates of existing MDI-QKD systems, identification of rate-limiting components, and projection of future performance. In addition, we also performed measurements over deployed fiber, showing that our system's performance is not affected by environment-induced perturbations.


Telerehabilitation for pelvic girdle dysfunction in pregnancy during COVID-19 pandemic crisis: A case report.
Pelvic girdle dysfunction is a common musculoskeletal disorder among pregnant women. It is a disabling condition affecting the ability of a pregnant woman to perform her daily functional activities. The scope of digital health in delivering rehabilitation services is growing exponentially, especially in the present COVID -19 pandemic crisis. A 29-year-old primigravida, at 32 weeks of gestation with severe pelvic girdle pain during bed transitions, sought physiotherapy consultation via video call, as she expressed difficulty in accessing Physiotherapy services due to the present pandemic crisis. Physiotherapy consultation was provided in 4 weekly sessions using a real-time video-based telerehabilitation program and the patient performed unsupervised exercise sessions for 30 minutes for 5 days per week for 4 weeks. The plan of care included muscle energy techniques, pelvic cloth belt, strengthening, stabilization exercises and stretching. The patient completed four sessions including evaluation and treatment and there was a reduction of pain scores for bed transitions from NPRS 8/10 during session one to NPRS 0/10 during session four. The Pelvic girdle dysfunction questionnaire showed a decrease in percentage scores from 54.6 to 4 at the end of physiotherapy sessions. Telerehabilitation was successfully used to manage a pregnant woman with pelvic girdle dysfunction.


Numerical predictions of the thermal behaviour and resultant effects of grouting cements while setting prosthetic components in bone.
Acrylic cements are commonly used to attach prosthetic components in joint replacement surgery. The cements set in short periods of time by a complex polymerization of initially liquid monomer compounds into solid structures with accompanying significant heat release. Two main problems arise from this form of fixation: the first is the potential damage caused by the temperature excursion, and the second is incomplete reaction leaving active monomer compounds, which can potentially be slowly released into the patient. This paper presents a numerical model predicting the temperature-time history in an idealized prosthetic-cement-bone system. Using polymerization kinetics equations from the literature, the degree of polymerization is predicted, which is found to be very dependent on the thermal history of the setting process. Using medical literature, predictions for the degree of thermal bone necrosis are also made. The model is used to identify the critical parameters controlling thermal and unreacted monomer distributions.


G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth.
Hypotrichosis simplex is a group of nonsyndromic human alopecias. We mapped an autosomal recessive form of this disorder to chromosome 13q14.11-13q21.33, and identified homozygous truncating mutations in P2RY5, which encodes an orphan G protein-coupled receptor. Furthermore, we identified oleoyl-L-alpha-lysophosphatidic acid (LPA), a bioactive lipid, as a ligand for P2Y5 in reporter gene and radioligand binding experiments. Homology and studies of signaling transduction pathways suggest that P2Y5 is a member of a subgroup of LPA receptors, which also includes LPA4 and LPA5. Our study is the first to implicate a G protein-coupled receptor as essential for and specific to the maintenance of human hair growth. This finding may provide opportunities for new therapeutic approaches to the treatment of hair loss in humans.


Content, Structure, and Delivery Characteristics of Yoga Interventions for Managing Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
This systematic review aimed to synthesize the content, structure, and delivery characteristics of effective yoga interventions used for managing hypertension and to compare these characteristics with ineffective interventions. The JBI and the PRISMA guidelines were followed in this systematic review. RCTs conducted among hypertensive adults were included. RCTs reporting at least one of the major components of yoga (i.e., asana, pranayama, and dhyana and relaxation practices) and comparing them with no intervention or any intervention were eligible. Sixteen databases were searched for published and unpublished studies without any date and language restrictions till March 15, 2021. The literature search yielded 13,130 records. 34 RCTs (evaluating 38 yoga interventions) met the inclusion criteria. Overall, included studies had low methodological quality mostly due to inadequate reporting. Yoga reduced SBP and DBP compared to a control intervention (MD -6.49 and -2.78; 95CI% -8.94- -4.04 and -4.11- -1.45, respectively). Eighteen, 14 and 20 interventions were effective in improving SBP, DBP, or either, respectively. 13 out of 20 effective interventions incorporated all the 3 major components of yoga and allocated similar durations to each component whereas ineffective interventions were more focused on the asana and duration of asana practice was longer. The most common duration and frequency of effective interventions were 45 min/session (in 5 interventions), 7 days/week (in 5 interventions), and 12 weeks (in 11 interventions) whereas the most common session frequency was 2 days a week (in 7 interventions) in ineffective interventions. Effective interventions were mostly center-based (in 15 interventions) and supervised (in 16 interventions) and this was similar with ineffective interventions. Despite the low quality and heterogeneity of included studies, our findings suggest yoga interventions may effectively manage hypertension. The differences between the effective and ineffective interventions suggest that effective yoga interventions mostly incorporated asana, pranayama, and dhyana and relaxation practices and they had a balance between these three components and included regular practice. They were mostly delivered in a center and under supervision. Future studies should consider developing and evaluating an intervention for managing hypertension using the synthesized findings of the effective interventions in this review. [PROSPERO], identifier [CRD42019139404].


Tissue Cytokine IL-33 Modulates the Cytotoxic CD8 T Lymphocyte Activity During Nutrient Deprivation by Regulation of Lineage-Specific Differentiation Programs.
IL-1 family member IL-33 exerts a variety of immune activating and regulating properties and has recently been proposed as a prognostic biomarker for cancer diseases, although its precise role in tumor immunity is unclear. Here we analyzed in vitro conditions influencing the function of IL-33 as an alarmin and a co-factor for the activity of cytotoxic CD8+ T cells in order to explain the widely discussed promiscuous behavior of IL-33 in vivo. Circulating IL-33 detected in the serum of healthy human volunteers was biologically inactive. Additionally, bioactivity of exogenous recombinant IL-33 was significantly reduced in plasma, suggesting local effects of IL-33, and inactivation in blood. Limited availability of nutrients in tissue causes necrosis and thus favors release of IL-33, which-as described before-leads to a locally high expression of the cytokine. The harsh conditions however influence T cell fitness and their responsiveness to stimuli. Nutrient deprivation and pharmacological inhibition of mTOR mediated a distinctive phenotype characterized by expression of IL-33 receptor ST2L on isolated CD8+ T cells, downregulation of CD8, a transitional CD45RAlowROlow phenotype and high expression of secondary lymphoid organ chemokine receptor CCR7. Under nutrient deprivation, IL-33 inhibited an IL-12 induced increase in granzyme B protein expression and increased expression of GATA3 and FOXP3 mRNA. IL-33 enhanced the TCR-dependent activation of CD8+ T cells and co-stimulated the IL-12/TCR-dependent expression of IFNγ. Respectively, GATA3 and FOXP3 mRNA were not regulated during TCR-dependent activation. TCR-dependent stimulation of PBMC, but not LPS, initiated mRNA expression of soluble IL-33 decoy receptor sST2, a control mechanism limiting IL-33 bioactivity to avoid uncontrolled inflammation. Our findings contribute to the understanding of the compartment-specific activity of IL-33. Furthermore, we newly describe conditions, which promote an IL-33-dependent induction of pro- or anti-inflammatory activity in CD8+ T cells during nutrient deprivation.


Transplantation Induces Profound Changes in the Transcriptional Asset of Hematopoietic Stem Cells: Identification of Specific Signatures Using Machine Learning Techniques.
During the phase of proliferation needed for hematopoietic reconstitution following transplantation, hematopoietic stem/progenitor cells (HSPC) must express genes involved in stem cell self-renewal. We investigated the expression of genes relevant for self-renewal and expansion of HSPC (operationally defined as CD34+ cells) in steady state and after transplantation. Specifically, we evaluated the expression of ninety-one genes that were analyzed by real-time PCR in CD34+ cells isolated from (i) 12 samples from umbilical cord blood (UCB); (ii) 15 samples from bone marrow healthy donors; (iii) 13 samples from bone marrow after umbilical cord blood transplant (UCBT); and (iv) 29 samples from patients after transplantation with adult hematopoietic cells. The results show that transplanted CD34+ cells from adult cells acquire an asset very different from transplanted CD34+ cells from cord blood. Multivariate machine learning analysis (MMLA) showed that four specific gene signatures can be obtained by comparing the four types of CD34+ cells. In several, but not all cases, transplanted HSPC from UCB overexpress reprogramming genes. However, these remarkable changes do not alter the commitment to hematopoietic lineage. Overall, these results reveal undisclosed aspects of transplantation biology.


The function of ascorbate oxidase in tobacco.
The function of the apoplastic enzyme ascorbate oxidase (AO) was investigated in tobacco (Nicotiana tabacum). The abundance of AO mRNA was up-regulated by light. Cytosolic ascorbate peroxidase (APX1) transcripts were also highest in the light. In contrast, L-galactono-gamma-lactone dehydrogenase, stromal APX, and thylakoid APX transcripts remained constant over the day/night cycle. Salicylic acid inhibited growth, increased expression of the pathogenesis-related protein (PR) 1a, and decreased AO transcript abundance. In contrast, the application of auxin enhanced growth and increased AO and PR 1a gene expression. Therefore, AO transcript abundance varied in a manner similar to hormone-mediated changes in plant growth. To study the effects of modified AO expression on growth, transformed tobacco plants expressing AO in the sense and antisense orientations were generated. The resultant large changes in apoplastic AO activity in the transformed tobacco plants had little effect on whole leaf ascorbate (AA) content, but they had dramatic effects on apoplastic AA levels. Enhanced AO activity oxidized the apoplastic AA pool, whereas decreased AO activity increased the amount of AA compared with dehydroascorbate. A relationship was observed between AO activity and plant height and biomass. Native AO transcript levels were no longer subject to light/dark regulation in AO sense and antisense plants. Taken together, these data show that there is an interaction between hormone, redox, and light signals at the level of the apoplast via modulation of ion of AA content.


Association of salivary Streptococcus mutans with caries in young children: effect of dental health education on salivary levels.
This study aimed to determine the effect of a long-term dental health education (DHE) for mothers with young children on the level of salivary Streptococci mutans (SM) and their association with caries in young children. A randomly selected cohort of 228 children born between 1 January and 30 September 1995, in a low socioeconomic high caries suburb of Leeds (UK), was divided into the following groups: A) DHE focused on diet; B) DHE focused on oral hygiene instruction (OHI) using fluoride toothpaste; C) DHE by a combined diet and OHI message. DHE was given using an interview and counselling for at least 15 minutes in each child's home, every three months for the first two years and twice a year in the third year of the study. A fourth group D was given diet and OHI, at home, but once a year only. The children in a fifth group E (control), received no DHE and were never visited, but examined at three years of age only. All children and mothers were examined for caries using the BASCD criteria. The levels of salivary SM were determined by sampling of bacteria from the oral cavity with a 1.8 cm wide wooden spatula, after giving the mother a paraffin pellet to chew for a minute and in children using unstimulated saliva. Bacteria were plated out and counted using image analysis for counting colonies. At three years of age the difference in the level of salivary SM between groups was not statistically significant. However, in group E there was a statistically significant relationship (p<0.05) between salivary SM and caries in children. The difference in the level of salivary SM between groups given various programs of dental health education was not statistically significant. There was a statistically significant (p<0.05) relationship between salivary MS and caries in children.


An adaptive toolbox approach to the route to expertise in sport.
Expertise is characterized by fast decision-making which is highly adaptive to new situations. Here we propose that athletes use a toolbox of heuristics which they develop on their route to expertise. The development of heuristics occurs within the context of the athletes' natural abilities, past experiences, developed skills, and situational context, but does not pertain to any of these factors separately. This is a novel approach because it integrates separate factors into a comprehensive heuristic description. The novelty of this approach lies within the integration of separate factors determining expertise into a comprehensive heuristic description. It is our contention that talent identification methods and talent development models should therefore be geared toward the assessment and development of specific heuristics. Specifically, in addition to identifying and developing separate natural abilities and skills as per usual, heuristics should be identified and developed. The application of heuristics to talent and expertise models can bring the field one step away from dichotomized models of nature and nurture toward a comprehensive approach to the route to expertise.


Fibrinolytic Therapy Improves Outcomes in Patients with Epidural Hematomas Following Cranioplasty: A Pilot Study.
Cranioplasty is a cosmetic procedure utilized to reconstruct cranial defects in patients following decompressive craniectomy. Epidural hematomas are a common complication of cranioplasty and often require surgical drainage. However, repeated surgery compromises patient safety and delays recovery. We investigated the development of epidural hematomas among 131 patients who underwent cranioplasty. Then we explored the efficacy of urokinase (UK) injection for the noninvasive treatment of epidural hematomas. We observed that 15 patients presented with epidural hematoma following cranioplasty. UK (30,000 IU/3 mL) was injected into the hematoma cavity twice every 12 hours in the first postoperative day. Next we closed the subgaleal drain for 1.5 hours and connected it with a negative-pressure ball on full vacuum to allow drainage. Binary logistic regression analysis was used to evaluate the risk factors associated with the development of epidural hematomas. Our findings demonstrated that a sunken skin flap was a risk factor for epidural hematoma formation (p = 0.006). The decrease in epidural hematoma volume was 35.27 ± 7.27 mL in the first 12 hours on postoperative day 1 after UK treatment. All treated patients whose Glasgow Coma Scale score did not significantly change despite the epidural hematoma had an uneventful recovery without additional complications and were discharged from the hospital, except for one patient. Fibrinolytic therapy can be considered an optional treatment for postoperative epidural hematoma associated with cranioplasty, especially in patients who refused further operative treatment or who are not optimal candidates for a second surgery.


Bare metal or drug-eluting stent versus drug-coated balloon in non-ST-elevation myocardial infarction: the randomised PEPCAD NSTEMI trial.
Drug-coated balloons (DCB) may avoid stent-associated long-term complications. This trial compared the clinical outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) treated with either DCB or stents. A total of 210 patients with NSTEMI were enrolled in a randomised, controlled, non-inferiority multicentre trial comparing a paclitaxel iopromide-coated DCB with primary stent treatment. The main inclusion criterion was an identifiable culprit lesion without angiographic evidence of large thrombus. The primary endpoint was target lesion failure (TLF; combined clinical endpoint consisting of cardiac or unknown death, reinfarction, and target lesion revascularisation) after nine months. Secondary endpoints included total major adverse cardiovascular events (MACE) and individual clinical endpoints. Mean age was 67±12 years, 67% were male, 62% had multivessel disease, and 31% were diabetics. One hundred and four patients were randomised to DCB, 106 to stent treatment. In the stent group, 56% of patients were treated with BMS, 44% with current-generation DES. In the DCB group, 85% of patients were treated with DCB only whereas 15% underwent additional stent implantation. During a follow-up of 9.2±0.7 months, DCB treatment was non-inferior to stent treatment with a TLF rate of 3.8% versus 6.6% (intention-to-treat, p=0.53). There was no significant difference between BMS and current-generation DES. The total MACE rate was 6.7% for DCB versus 14.2% for stent treatment (p=0.11), and 5.9% versus 14.4% in the per protocol analysis (p=0.056), respectively. In patients with NSTEMI, treatment of coronary de novo lesions with DCB was non-inferior to stenting with BMS or DES. These data warrant further investigation of DCB in this setting, in larger trials with DES as comparator (ClinicalTrials.gov Identifier: NCT01489449).


RETRACTED: Understanding farmers' safety behaviour towards pesticide exposure and other occupational risks: The case of Zanjan, Iran.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of request of the Editors-in-Chief. After a thorough investigation, the Editors have concluded that the acceptance of this article was partly based upon the positive advice of one illegitimate reviewer report. The report was submitted from an email account which was provided by the corresponding author Christos A. Damalas as a suggested reviewer during the submission of the article. Although purportedly a real reviewer account, the Editors have concluded that this was not of an appropriate, independent reviewer. This manipulation of the peer-review process represents a clear violation of the fundamentals of peer review, our publishing policies, and publishing ethics standards. Apologies are offered to the reviewer whose identity was assumed and to the readers of the journal that this deception was not detected during the submission process.


Multicentre magnetic resonance texture analysis trial using reticulated foam test objects.
Texture analysis in magnetic resonance imaging has the ability to provide useful diagnostic information with respect to the discrimination of disease states of a single tissue or the separation of different tissues. However, for widespread use it is necessary to determine how texture measurements carried out in one center relate to those carried out in another. To this end, a multicentre trial has been performed where reticulated foam test objects have been scanned in six European centers according to a fixed protocol. It has been concluded that texture measurements are not transportable between centers. Principal component models calculated from the texture parameters collected in one center do not fit the data collected in another. Further trials are to investigate whether the reticulated foam test objects may be used to normalize tissue texture data collected in different centers.


The myeloid 7/4-antigen defines recently generated inflammatory macrophages and is synonymous with Ly-6B.
This study aimed to identify the inflammation-associated 7/4-antigen, which is highly expressed on neutrophils, inflammatory monocytes, some activated macrophages, as well as on bone marrow myeloid-restricted progenitors. The high expression on inflammatory cells is suggestive of a role in inflammation and makes the 7/4-antigen a potential target for the manipulation of inflammatory cells. Consistent with this, the 7/4-antibody mediates specific depletion of 7/4-expressing neutrophils and monocytes. We have identified the 7/4-antigen as a 25- to 30-kDa GPI-anchored glycoprotein synonymous with the Ly-6B.2 alloantigen. We characterized the expression of Ly-6B during the inflammatory reaction induced by zymosan. During the later stages of an experimental, acute, self-resolving inflammatory response, we found that Ly-6B is differentially expressed on macrophages. Ly-6B-expressing macrophages also express more MHCII, CIITA, CCR2, Ly-6C, and CD62L than the Ly-6B-negative macrophages, which in turn, express more of the resident tissue macrophage marker SIGN-R1 and higher CD11b and F4/80. Ly-6B-expressing macrophages incorporate more BrdU than their Ly-6B-negative contemporaries when fed during the resolution phase of the acute inflammatory response. Thus, Ly-6B expression on mature macrophages defines a subset of recently generated inflammatory macrophages that retain monocytic markers and is hence a surrogate marker of macrophage turnover in inflammatory lesions. The definition of the 7/4:Ly-6B antigen will allow further characterization and specific modulation of Ly-6B-expressing cells in vivo.


Polyimide-Doped Indium-Gallium-Zinc Oxide-Based Transparent and Flexible Phototransistor for Visible Light Detection.
We report a transparent and flexible polyimide (PI)-doped single-layer (PSL) phototransistor for the detection of visible light. The PSL was deposited on a SiO2 gate insulator by a co-sputtering process using amorphous indium-gallium-zinc oxide (IGZO) and PI targets simultaneously. The PSL acted as both a channel layer and a visible-light absorption layer. PI is one of the few flexible organic materials that can be fabricated into sputtering targets. Compared with the IGZO phototransistor without PI doping, the PSL phototransistor exhibited improved optoelectronic characteristics under illumination with 635 nm red light of 1 mW/mm2 intensity; the obtained photoresponsivity ranged from 15.00 to 575.00 A/W, the photosensitivity from 1.38 × 101 to 9.86 × 106, and the specific detectivity from 1.35 × 107 to 5.83 × 1011 Jones. These improvements are attributed to subgap states induced by the PI doping, which formed decomposed organic molecules, oxygen vacancies, and metal hydroxides. Furthermore, a flexible PSL phototransistor was fabricated and showed stable optoelectronic characteristics even after 10,000 bending tests.


[Effect of electroshock convulsions on caudate nucleus function].
In unrestrained cats, after the electro--shock seizures, the afamphetamine--indused stereotype, behavior was increased and the caudate circular response to high--frequency stimulation was facilitated. The delayed response to low-frequency stimulation of the caudate nucleus was, on the contrary, decreased. Thresholds of the circular and delayed responses to stimulation of the thalamus and capsula interna did not change in the post--seizure period. The above shifts are supposed to be due to weakening of the caudate nucleus inhibitory function resulting from the electro--shock--evoked increase in the caudate dophamine.


Effects of Subdural Monopolar Cortical Stimulation Paired With Rehabilitative Training on Behavioral and Neurophysiological Recovery After Cortical Ischemic Stroke in Adult Squirrel Monkeys.
Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enhancing poststroke functional recovery in rats, but human clinical trials have had mixed outcomes. To assess the efficacy of CS/RT versus RT in a nonhuman primate model of cortical ischemic stroke. Squirrel monkeys learned a pellet retrieval task, then received an infarct to the distal forelimb (DFL) representation of primary motor cortex. A subdural monopolar electrode was implanted over the spared DFL representation in dorsal premotor cortex (PMD). Seven weeks postinfarct, monkeys underwent 4 to 6 weeks of RT (n = 8) or CS/RT (n = 7; 100 Hz, cathodal current) therapy. Behavioral performance was assessed before and after infarct, prior to therapy, and 1 and 12 weeks posttherapy (follow-up). The primary outcome measure was motor performance at 1 week posttherapy. Secondary outcomes included follow-up performance at 12 weeks and treatment-related changes in neurophysiological maps of spared DFL representations. While postinfarct performance deficits were found in all monkeys, both groups demonstrated similar recovery profiles, with no difference in motor recovery between the RT and CS/RT groups. Posttherapy, PMD DFL area was significantly expanded in the RT group but not the CS/RT group. A significant relationship was found between motor recovery and DFL expansion in premotor cortex. Results suggest that the specific parameters utilized here were not optimal for promoting behavioral recovery in nonhuman primates. Though CS/RT has consistently shown efficacy in rat stroke models, the present finding has cautionary implications for translation of CS/RT therapy to clinical populations.


Selection of coxsackievirus B4 variants with monoclonal antibodies results in attenuation.
Inoculation of suckling mice with coxsackievirus B4 (CB4) results in the death of a majority of the animals. In this study we selected antigenic variants of CB4 in the presence of neutralizing monoclonal antibodies and tested them to see whether they were attenuated. Antigenic variants selected with a single antibody showed little or no attenuation by producing a high mortality (60 to 100%). A double variant selected with two antibodies showed considerable attenuation by causing only 25% mortality. A triple variant selected with three antibodies was almost completely attenuated (killed only 5% of the animals). Polypeptides from these variants were tested for their ability to interact with the monoclonal antibodies used for their selection. These studies showed that resistance of variant virus to neutralization in general was due to the inability of the antibody to bind to the virus. However, one of the antibodies could bind but not neutralize the virus, perhaps due to an alteration in the epitope. It is concluded that selection of CB4 variants using more than one neutralizing monoclonal antibody can lead to attenuation of the virus.


Cellsketch: Simplified Cell Representation for Label-free Cell and Nuclei Segmentation.
This paper presents a novel technique for cell segmentation, named "Cellsketch," which generates an RGB mask containing simplified representations of cells (including nuclei, whole-cell, and cell boundaries) from microscopic images, and applies the watershed algorithm to produce segmentation masks of cells and nuclei. The RGB mask is generated using a generator model trained with a combination of L1 loss and adversarial loss. The method achieved accurate cell and nuclei segmentation from differential interference contrast (DIC) images using only automatically annotated training data and shows potential for a generalizable algorithm for cell segmentation. The code is freely available at: https://github.com/iranovianti/cellsketchClinical Relevance- This method simultaneously detects individual cells and nuclei from DIC images.


Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential.
The KRAB domain is a highly conserved transcription repression module commonly found in eukaryotic zinc finger proteins. KRAB-mediated repression requires binding to the KAP-1 corepressor, which in turn recruits members of the heterochromatin protein 1 (HP1) family. The HP1 proteins are nonhistone chromosomal proteins, although it is unclear how they are targeted to unique chromosomal domains or promoters. In this report, we have reconstituted and characterized the HP1-KAP-1 interaction using purified proteins and have compared KAP-1 to three other known HP1 binding proteins: SP100, lamin B receptor (LBR), and the p150 subunit from chromatin assembly factor (CAF-1 p150). We show that the chromoshadow domain (CSD) of HP1 is a potent repression domain that binds directly to all four previously described proteins. For KAP-1, we have mapped the CSD interaction region to a 15-amino-acid segment, termed the HP1BD, which is also present in CAF-1 p150 but not SP100 or LBR. The region of KAP-1 harboring the HP1BD binds as a monomer to a dimer of the CSD, as revealed by gel filtration, analytical ultracentrifugation, and optical biosensor analyses. The use of a spectrum of amino acid substitutions in the human HP1alpha CSD revealed a strong correlation between CSD-mediated repression and binding to KAP-1, CAF-1 p150, and SP100 but not LBR. Differences among the HP1 binding partners could also be discerned by fusion to a heterologous DNA binding domain and by the potential to act as dominant negative molecules. Together, these results strongly suggest that KAP-1 is a physiologically relevant target for HP1 function.


The interaction between St John's wort and an oral contraceptive.
The popular herbal remedy St John's wort is an inducer of cytochrome P450 (CYP) 3A enzymes and may reduce the efficacy of oral contraceptives. Therefore we evaluated the effect of St John's wort on the disposition and efficacy of Ortho-Novum 1/35 (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a popular combination oral contraceptive pill containing ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). Twelve healthy premenopausal women who were using oral contraception (>3 months) received a combination oral contraceptive pill (Ortho-Novum 1/35) for 3 consecutive 28-day menstrual cycles. During the second and third cycles, the participants received 300 mg St John's wort 3 times a day. The serum concentrations of ethinyl estradiol (day 7), norethindrone (day 7), follicle-stimulating hormone (days 12-16), luteinizing hormone (days 12-16), progesterone (day 21), and intravenous and oral midazolam (days 22 and 23) were determined in serial blood samples. The incidence of breakthrough bleeding was quantified during the first and third cycles. Concomitant use of St John's wort was associated with a significant (P <.05) increase in the oral clearance of norethindrone (8.2 +/- 2.7 L/h to 9.5 +/- 3.4 L/h, P =.042) and a significant reduction in the half-life of ethinyl estradiol (23.4 +/- 19.5 hours to 12.2 +/- 7.1 hours, P =.023). The oral clearance of midazolam was significantly increased (109.2 +/- 47.9 L/h to 166.7 +/- 81.3 L/h, P =.007) during St John's wort administration, but the systemic clearance of midazolam was unchanged (37.7 +/- 11.3 L/h to 39.0 +/- 10.3 L/h, P =.567). Serum concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone were not significantly affected by St John's wort dosing (P >.05). Breakthrough bleeding occurred in 2 of 12 women in the control phase compared with 7 of 12 women in the St John's wort phase. The oral clearance of midazolam after St John's wort dosing was greater in women who had breakthrough bleeding (215.9 +/- 66.5 L/h) than in those who did not (97.5 +/- 37.2 L/h) (P =.005). St John's wort causes an induction of ethinyl estradiol-norethindrone metabolism consistent with increased CYP3A activity. Women taking oral contraceptive pills should be counseled to expect breakthrough bleeding and should consider adding a barrier method of contraception when consuming St Johns wort.


Detection of Echinocandin-Resistant Candida glabrata in Blood Cultures Spiked with Different Percentages of FKS2 Mutants.
Infections caused by the coexistence of Candida glabrata echinocandin-resistant and echinocandin-susceptible cells may be possible, and the detection of FKS mutants when the proportions of FKS mutants are underrepresented poses a problem. We assessed the role of EUCAST and methods directly performed on positive blood cultures-Etest (ETDIR) and anidulafungin-containing agar plate assays-for detecting resistance in C. glabrata isolates containing different amounts of echinocandin-susceptible and -resistant Candida glabrata isolates. We studied 10 pairs of C. glabrata isolates involving parental echinocandin-susceptible isolates and isogenic echinocandin-resistant FKS mutant isolates. Three inocula per pair (1 × 103 to 5 × 103, 1 × 102 to 5 × 102, and 10 to 50 CFU/ml) spanning suspensions with different amounts of susceptible/resistant isolates (9/1, 5/5, and 1/9 proportions for each the three inocula) were prepared. The suspensions were spiked in Bactec bottles and incubated until they were positive, and the three methods were compared. The EUCAST method showed echinocandin resistance when the bottles were spiked with susceptible/resistant isolates at 5/5 and 1/9 proportions; the results for the suspensions with a 9/1 proportion of susceptible/resistant isolates were susceptible for three pairs. We observed with the ETDIR resistance to both echinocandins in all pairs (resistance to micafungin and anidulafungin; MICs, ≥0.064 mg/liter and ≥0.125 mg/liter, respectively) and a double ring of growth inhibition in two pairs. The anidulafungin-containing plates showed fungal growth in the 90 spiked blood cultures at 48 h. Testing of echinocandin susceptibility with the ETDIR directly on the positive blood culture bottles is a reliable and rapid method to detect echinocandin resistance in C. glabrata On the other hand, resistance can be missed with the EUCAST method when resistant isolates are underrepresented.


Effects of statins on skeletal muscle: a perspective for physical therapists.
Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy.


NF-kappaB Signaling Pathways in Neurological Inflammation: A Mini Review.
The NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) transcription factor family is a pleiotropic regulator of many cellular signaling pathways, providing a mechanism for the cells in response to a wide variety of stimuli linking to inflammation. The stimulated cells will be regulated by not only the canonical but also non-canonical NF-κB pathways. To initiate both of these pathways, IκB-degradation triggers NF-κB release and the nuclear translocated-heterodimer (or homodimer) can associate with the κB sites of promoter to regulate the gene transcriptions. NF-κB ubiquitously expresses in neurons and the constitutive NF-κB activation is associated with processing of neuronal information. NF-κB can regulate the transcription of genes such as chemokines, cytokines, proinflammatory enzymes, adhesion molecules, proinflammatory transcription factors, and other factors to modulate the neuronal survival. In neuronal insult, NF-κB constitutively active in neuron cell bodies can protect neurons against different injuries and regulate the neuronal inflammatory reactions. Besides neurons, NF-κB transcription factors are abundant in glial cells and cerebral blood vessels and the diverse functions of NF-κB also regulate the inflammatory reaction around the neuronal environment. NF-κB transcription factors are abundant in the brain and exhibit diverse functions. Several central nerve system (CNS) diseases are linked to NF-κB activated by inflammatory mediators. The RelA and c-Rel expression produce opposite effects on neuronal survival. Importantly, c-Rel expression in CNS plays a critical role in anti-apoptosis and reduces the age-related behaviors. Moreover, the different subunits of NF-κB dimer formation can modulate the neuroninflammation, neuronal protection, or neurotoxicity. The diverse functions of NF-κB depend on the subunits of the NF-κB dimer-formation which enable us to develop a therapeutic approach to neuroinflammation based on a new concept of inflammation as a strategic tool in neuronal cells. However, the detail role of NF-κB in neuroinflammation, remains to be clarified. In the present article, we provide an updated review of the current state of our knowledge about relationship between NF-κB and neuroinflammation.


Consequences of a benzodiazepine discontinuation programme in family practice on psychotropic medication prescription to the participants.
Whether long-term benzodiazepine users who participate in a family practice-based benzodiazepine discontinuation programme substitute benzodiazepines by other psychotropics is not clear. To evaluate the impact of a benzodiazepine discontinuation programme on non-benzodiazepine psychotropic prescription in family practice. In family practices in the Netherlands, 2425 long-term benzodiazepine users participated in a two-step benzodiazepine discontinuation programme. The programme started with a discontinuation letter (Step 1). Subjects unable to stop (N = 1707) were offered participation in Step 2, a three-group randomized trial with a taper procedure with group psychotherapy, a taper without psychotherapy and usual care. Only 156 subjects agreed to participate. The comparison group consisted of 1821 long-term users from family practices not participating in the programme. The main outcome was the change in prescription of non-benzodiazepine psychotropic medication from baseline (3 months before the start of the programme) till 21 months after the start of the programme. Four logistic regression models were performed concerning antidepressant prescription in the follow-up. Only antidepressants were prescribed in relevant numbers. The prescription of antidepressants was not related to the programme. (P-value of experimental versus control group varied between 0.18 and 0.85 in the four models). The most important predictor of antidepressant prescription in follow-up was baseline antidepressant prescription [odds ratio (OR): 67.2; 95% confidence interval (95% CI): 49.8-90.7]. Subjects, of whom the prescription of benzodiazepines had been discontinued completely, had been prescribed less antidepressants (OR: 0.8; 95% CI: 0.6-1.0). An effective benzodiazepine reduction programme was not accompanied by a substitute use of other psychotropics.


[Esophageal Cancer Initially Presenting as Severe Paraneoplastic Hypercalcemia Requiring Hemodialysis].
Paraneoplastic hypercalcemia without bone metastasis occurs rarely in esophageal cancer. A 75-year-old man was admitted for general weakness and lethargy. Laboratory data showed high serum calcium level (corrected calcium 14.6 mg/dL), low parathyroid hormone level (3.3 pg/mL) and high parathyroid hormone-related peptide level (3.5 pmol/L). Esophagogastroscopy showed a malignant tumor in the esophagus. Histology showed moderately differentiated squamous cell carcinoma. Bone scan showed no evidence of bone metastasis. Since the patient's calcium levels remained high and mental state did not show improvement despite intravenous fluid therapy, diuretics and intravenous bisphosphonate, hemodialysis was started. After hemodialysis treatment, the serum calcium level subsequently normalized and his mental status improved. Herein, we report a rare case of paraneoplastic hypercalcemia in a patient with esophageal cancer.


Induction of programmed cell death in lily by the fungal pathogen Botrytis elliptica.
SUMMARY The genus Botrytis contains necrotrophic plant pathogens that have a wide host range (B. cinerea) or are specialized on a single host species, e.g. B. elliptica on lily. In this study, it was found that B. elliptica-induced cell death of lily displays hallmark features of animal programmed cell death or apoptosis including cytoplasmic shrinkage, nuclear DNA fragmentation and the accumulation of NO as well as H(2)O(2). A pharmacological approach showed that B. elliptica-induced cell death could be modulated by serine and cysteine protease inhibitors including one caspase inhibitor. Blocking phosphatase activity stimulated cell death and concomitant lesion formation, suggesting that B. elliptica-induced cell death is mediated by kinase/phosphatase pathways. Blocking Ca(2+) influx restricted cell death. Blocking steps of sphingolipid biosynthesis delayed lily cell death for several days. B. elliptica culture filtrate (CF) was able to induce lily cell death by means of secreted proteins. Induction of cell death is necessary and sufficient for pathogenicity and host specialization because prior infiltration of B. elliptica CF enabled subsequent infection of lily by the otherwise incompatible pathogens B. cinerea and B. tulipae. The secreted B. elliptica proteins also induced cell death in some but not all Arabidopsis accessions and mutants. Arabidopsis accessions that respond to infiltration of B. elliptica CF also display cell death symptoms upon inoculation with B. elliptica conidia.


The Schistosoma japonicum self-cure phenomenon in water buffaloes: potential impact on the control and elimination of schistosomiasis in China.
Schistosomiasis japonica, caused by Schistosoma japonicum, is an important zoonotic disease in China, the Philippines and small pockets of Indonesia. In addition to infecting people, S. japonicum can infect over 40 species of wild and domestic animals which have varying impacts on human infection. It is now generally accepted that bovines, particularly water buffaloes, are the major reservoir for human infection in China as they are naturally infected with schistosomes and deposit more eggs into the environment than humans or any other animal host. This complicates control efforts and the economic burden associated with schistosomiasis morbidity and mortality has taken its toll on both human and livestock populations. Over the last 50years, the schistosomiasis control program in China has made great strides in reducing prevalence and morbidity, and the Chinese authorities now aim to eliminate the disease nationwide in the next decade. Current Chinese control strategies place particular importance on interventions targeting bovines including: praziquantel treatment, barrier farming to prevent grazing in transmission areas, their replacement with mechanized tractors and possible bovine vaccination. A number of studies have shown that in the period following S. japonicum infection, the worm burden drops sharply in water buffaloes and some other animal hosts such as pigs. This is due to a self-cure phenomenon whereby there is parasite clearance by both immune and non-immune factors. Here we review studies investigating the self-cure effect, paying particular attention to S. japonicum infection in water buffaloes, and discuss its potential impact on the future schistosomiasis control and elimination efforts in China. Further understanding of the mechanism of self-cure in water buffaloes could be important for future schistosome vaccine design and delivery.


Assessing discriminative ability of risk models in clustered data.
The discriminative ability of a risk model is often measured by Harrell's concordance-index (c-index). The c-index estimates for two randomly chosen subjects the probability that the model predicts a higher risk for the subject with poorer outcome (concordance probability). When data are clustered, as in multicenter data, two types of concordance are distinguished: concordance in subjects from the same cluster (within-cluster concordance probability) and concordance in subjects from different clusters (between-cluster concordance probability). We argue that the within-cluster concordance probability is most relevant when a risk model supports decisions within clusters (e.g. who should be treated in a particular center). We aimed to explore different approaches to estimate the within-cluster concordance probability in clustered data. We used data of the CRASH trial (2,081 patients clustered in 35 centers) to develop a risk model for mortality after traumatic brain injury. To assess the discriminative ability of the risk model within centers we first calculated cluster-specific c-indexes. We then pooled the cluster-specific c-indexes into a summary estimate with different meta-analytical techniques. We considered fixed effect meta-analysis with different weights (equal; inverse variance; number of subjects, events or pairs) and random effects meta-analysis. We reflected on pooling the estimates on the log-odds scale rather than the probability scale. The cluster-specific c-index varied substantially across centers (IQR = 0.70-0.81; I2 = 0.76 with 95% confidence interval 0.66 to 0.82). Summary estimates resulting from fixed effect meta-analysis ranged from 0.75 (equal weights) to 0.84 (inverse variance weights). With random effects meta-analysis - accounting for the observed heterogeneity in c-indexes across clusters - we estimated a mean of 0.77, a between-cluster variance of 0.0072 and a 95% prediction interval of 0.60 to 0.95. The normality assumptions for derivation of a prediction interval were better met on the probability than on the log-odds scale. When assessing the discriminative ability of risk models used to support decisions at cluster level we recommend meta-analysis of cluster-specific c-indexes. Particularly, random effects meta-analysis should be considered.


A social mandate: APN leadership for the whole policy process.
Advanced practice nurses (APNs) have a societal mandate to shape public policy. Thus nurses must be knowledgeable about the entire process of developing public policy, not just the legislative aspect. The policy process encompasses agenda setting; government response in the form of laws, regulations, and programs; and the design, implementation, and evaluation of policies and programs. The education and experience of APNs can provide innovative responses to a wide array of health-related problems.


Familial B-cell chronic lymphocytic leukemia in a population of patients from Southern Italy.
We investigated the prevalence of chronic lymphocytic leukemia (CLL) in 9650 relatives of 510 CLL patients from 5 different regions (Apulia, Basilicata, Campania, Calabria, and Sicily) of Southern Italy. Data collection included a family history questionnaire. In our series of 510 CLL patients, 53 families with 2 or more individuals who had chronic lymphoproliferative disease (CLD) or other hematological malignancies were identified. In these families, 27 cases of CLL, 10 of indolent non-Hodgkin's lymphoma, and 7 of multiple myeloma were identified in relatives of CLL probands. Twenty-two relatives developed hematological malignancies other than CLD (19, acute leukemia; 3, chronic myeloid leukemia). In this study the prevalence of CLD in relatives of 510 CLL patients was 8.6% (44/510), and the prevalence of CLL in the same series was 5.2% (27/ 510). Considering the presence of clusters of individuals with hematological malignancies, overall our series contained 4 families showing a cluster with more than 2 cases. The most frequent pattern of affected family members was represented by 39 families (39/53 [73%]) with affected siblings or cousins only. Twenty siblings had CLL. The other families showed a multigenerational pattern with an affected parent-offspring relationship in only 11 (21%) of the cases and with a combination of the first 2 categories in 3 (6%) of the families. In 8 families belonging to both the last 2 mentioned groups, the affected offspring had an earlier disease onset than their parents, suggesting anticipation. We estimated the size and examined the pattern of familial aggregation of hematological malignancies, in particular CLL/CLD, in a specific geographical area. CLL was the most frequent disease in relatives, mainly siblings, of our CLL patients. Our results may be a contribution to the characterization of the epidemiological distribution pattern of CLL.


Targeted strategies for the management of wildlife diseases: the case of brucellosis in Alpine ibex.
The management of infectious diseases in wildlife reservoirs is challenging and faces several limitations. However, detailed knowledge of host-pathogen systems often reveal heterogeneity among the hosts' contribution to transmission. Management strategies targeting specific classes of individuals and/or areas, having a particular role in transmission, could be more effective and more acceptable than population-wide interventions. In the wild population of Alpine ibex (Capra ibex-a protected species) of the Bargy massif (French Alps), females transmit brucellosis (Brucella melitensis) infection in ~90% of cases, and most transmissions occur in the central spatial units ("core area"). Therefore, we expanded an individual-based model, developed in a previous study, to test whether strategies targeting females or the core area, or both, would be more effective. We simulated the relative efficacy of realistic strategies for the studied population, combining test-and-remove (euthanasia of captured animals with seropositive test results) and partial culling of unmarked animals. Targeting females or the core area was more effective than untargeted management options, and strategies targeting both were even more effective. Interestingly, the number of ibex euthanized and culled in targeted strategies were lower than in untargeted ones, thus decreasing the conservation costs while increasing the sanitary benefits. Although there was no silver bullet for the management of brucellosis in the studied population, targeted strategies offered a wide range of promising refinements to classical sanitary measures. We therefore encourage to look for heterogeneity in other wildlife diseases and to evaluate potential strategies for improving management in terms of efficacy but also acceptability.


Relationship between immediate post-operative appearance and 6-week operative outcome in trichiasis surgery.
Surgical technique, including suture placement and tension, is believed to contribute to the outcome of bilamellar tarsal rotation surgery for trachomatous trichiasis. However, the immediate post-operative appearance that minimizes the chance of recurrence and other adverse outcomes has not been investigated. To explore whether the degree of correction immediately after surgery is predictive of surgical outcome at the 6-week post-operative visit, photographs taken immediately after surgery were used to predict surgical outcomes, including the severity of eyelid contour abnormality and trichiasis recurrence. Both eyelid contour abnormalities and recurrence were accurately predicted from the immediate post-operative photographs by an experienced oculoplastic surgeon 85% and 70% of the time, respectively. Participants with a "slight over-correction" that resulted in no eyelid contour abnormality and no recurrence were used to identify immediate post-operative contours that lead to a successful surgical outcome. The immediate post-operative eyelid contour is an important indicator of post-operative success of BLTR surgery. Based upon our findings, we developed a Surgery Photocard. This card illustrates some examples of immediate post-surgical appearances, which led to a successful outcome, as well as sub-optimal appearances, which led to poor surgical outcomes. The card also provides suggestions for improving the appearance by adjusting the suture placement or tension based upon standard oculoplastic principles.


On the effect of changing handgrip position on joint specific power and cycling kinematics in recreational and professional cyclists.
In cycling, the utilization of the drops position (i.e. the lowest handlebar position relative to the ground) allows for reduced frontal area, likely improved aerodynamics and thus performance compared to the tops (i.e. the position producing the most upright trunk). The reduced trunk angle during seated submaximal cycling has been shown to influence cardiorespiratory factors but the effects on pedalling forces and joint specific power are unclear. The purpose of this study was to investigate the effect of changing handgrip position on joint specific power and cycling kinematics at different external work rates in recreational and professional cyclists. Nine professional and nine recreational cyclists performed cycling bouts using three different handgrip positions and three external work rates (i.e. 100W, 200W and external work rate corresponding to the lactate threshold (WRlt)). Joint specific power was calculated from kinematic measurements and pedal forces using 2D inverse dynamics. We found increased hip joint power, decreased knee joint power and increased peak crank torque for the professional cyclist compared to the recreational cyclists, but only at WRlt where the professional cyclists were working at a higher external work rate. There was no main effect of changing handgrip position on any joint, but there was a small interaction effect of external work rate and handgrip position on hip joint power contribution (Generalized eta squared (ηg2) = 0.012). At 100W, changing handgrip position from the tops to the drops decreased the hip joint contribution (-2.0 ± 3.9 percentage points (pct)) and at the WRlt, changing handgrip position increased the hip joint power (1.6 ± 3.1 pct). There was a small effect of handgrip position with the drops leading to increased peak crank torque (ηg2 = 0.02), increased mean dorsiflexion (ηg2 = 0.05) and increased hip flexion (ηg2 = 0.31) compared to the tops. The present study demonstrates that there is no main effect of changing handgrip position on joint power. Although there seems to be a small effect on hip joint power when comparing across large ranges in external work rate, any potential negative performance effect would be outweighed by the aerodynamic benefit of the drops position.


Socioeconomic conditions of elderly people in Kosovo: a cross-sectional study.
Kosovo is the newest state in Europe facing a particularly difficult socioeconomic and political transition. The available evidence on socioeconomic conditions and quality of life of elderly people in Kosovo is scarce notwithstanding the ageing trend due to lowering of fertility rates and a higher life-expectancy. In this context, the aim of our study was to assess the socioeconomic conditions of elderly people in post-war Kosovo. A cross-sectional study was conducted in Kosovo in January-March 2011 including an age- sex-and residence (urban vs. rural)-stratified sample of 1,890 individuals (83.5% response) aged 65 years and over. A structured questionnaire included assessment of socio-demographic and socioeconomic characteristics including educational level and self-perceived poverty. Binary logistic regression was used to assess the association of self-perceived poverty with socio-demographic and socioeconomic factors. The educational level in this representative sample of elderly people in Kosovo was quite low, particularly among women. About 47% of respondents perceived themselves as poor, or extremely poor (41% of men and 52% of women). In multivariable-adjusted models, self-perceived poverty was higher among older women, low educated individuals, urban residents, and elderly individuals living alone. Findings from this study indicate that the socioeconomic situation of the elderly population in Kosovo is rather challenging. Demographic trends coupled with the economic and political transition raise serious concerns about increasing needs for socioeconomic support of elderly people in Kosovo. Specific policies and actions should be considered by a number of stakeholders, including government and civil society in transitional Kosovo.


Use of a fiber optic probe for spectral measurements and the continuous recording of the turbidity of growing microbial cultures.
This paper describes the properties and use of a fiber optic probe as an attachment to a spectrophotometer and its use for measurements in solutions and turbid suspensions. Measurements of a standard were identical when a spectrophotometer equipped with the probe was used or when a spectrophotometer was used in a conventional manner. The probe was calibrated for turbidimetric measurements with microorganisms by relating the apparent absorbancy measured on the spectrophotometer to the dry weight of each species of organism. Continuous measurements were made of the turbidity of growing cultures of Escherichia coli, Streptococcus mutans, and Saccharomyces cerevisiae. Transient changes in cell mass were observed in some cultures during continuous monitoring of growth. The data were recovered in a manner which allowed direct computer processing.


Sarcomeric deficits underlie MYBPC1-associated myopathy with myogenic tremor.
Myosin binding protein-C slow (sMyBP-C) comprises a subfamily of cytoskeletal proteins encoded by MYBPC1 that is expressed in skeletal muscles where it contributes to myosin thick filament stabilization and actomyosin cross-bridge regulation. Recently, our group described the causal association of dominant missense pathogenic variants in MYBPC1 with an early-onset myopathy characterized by generalized muscle weakness, hypotonia, dysmorphia, skeletal deformities, and myogenic tremor, occurring in the absence of neuropathy. To mechanistically interrogate the etiologies of this MYBPC1-associated myopathy in vivo, we generated a knock-in mouse model carrying the E248K pathogenic variant. Using a battery of phenotypic, behavioral, and physiological measurements spanning neonatal to young adult life, we found that heterozygous E248K mice faithfully recapitulated the onset and progression of generalized myopathy, tremor occurrence, and skeletal deformities seen in human carriers. Moreover, using a combination of biochemical, ultrastructural, and contractile assessments at the level of the tissue, cell, and myofilaments, we show that the loss-of-function phenotype observed in mutant muscles is primarily driven by disordered and misaligned sarcomeres containing fragmented and out-of-register internal membranes that result in reduced force production and tremor initiation. Collectively, our findings provide mechanistic insights underscoring the E248K-disease pathogenesis and offer a relevant preclinical model for therapeutic discovery.


Global tropospheric and total ozone monitoring with a double-etalon fabry-perot interferometer. I. Instrument concept.
The global distribution of tropospheric ozone (O(3)) can be observed from a satellite-based instrument by spectrally isolating the pressure-broadened wings of strong O(3) lines. The Fabry-Perot interferometer (FPI) provides high spectral resolution and high-throughput capabilities that are essential for performing such a measurement. Through proper selection of channel spectral regions, the FPI optimized for tropospheric O(3) measurements can simultaneously observe a stratospheric component and thus the total O(3) column abundance. We present a conceptual instrument design that involves a double-etalon fixed-gap series configuration FPI along with an ultranarrow bandpass filter to achieve single-order operation with an overall spectral resolution of approximately 0.068 cm(-1), sampling the narrow 1054.2-1055.2 cm(-1) spectral region within the strong 9.6-mum ozone infrared band from a nadir-viewing satellite configuration.


Confined Ni nanoparticles in N-doped carbon nanotubes for excellent pH-universal industrial-level electrocatalytic CO2 reduction and Zn-CO2 battery.
Electrocatalytic reduction of CO2 (ECR) offers a promising approach to curbed carbon emissions and complete carbon cycles. However, the inevitable creation of carbonates and limited CO2 utilization efficiency in neutral or alkaline electrolytes result in low energy efficiency, carbon losses and its widespread commercial utilization. The advancement of CO2 reduction under acidic conditions offers a promising approach for their commercial utilization, but the inhibition of hydrogen evolution reaction and the corrosion of catalysts are still challenging. Herein, Ni nanoparticles (NPs) wrapped in N-doped carbon nanotubes (NixNC-a) are successfully prepared by a facile mixed-heating and freeze-drying method. Ni100NC-a achieves a high Faraday efficiency (FE) of near 100 % for CO under pH-universal conditions, coupled with a promising current density of CO (>100 mA cm-2). Especially in acidic conditions, Ni100NC-a exhibits an exceptional ECR performance with the high FECO of 97.4 % at -1.44 V and the turnover frequency (TOF) of 11 k h-1 at -1.74 V with a current density of 288.24 mA cm-2. This excellent performance is attributed to the synergistic effect of Ni NPs and N-doped carbon shells, which protects Ni NPs from etching, promotes CO2 adsorption and regulates local pH. Moreover, Ni100NC-a could drive the reversible Zn-CO2 battery with a high power-density of 4.68 mW cm-2 and a superior stability (98 h). This study presents a promising candidate for efficient pH-universal CO2 electroreduction and Zn-CO2 battery.


Protection of the general stress response σS factor by the CrsR regulator allows a rapid and efficient adaptation of Shewanella oneidensis.
To cope with environmental stresses, bacteria have evolved various strategies, including the general stress response (GSR). GSR is governed by an alternative transcriptional σ factor named σS (RpoS) that associates with RNA polymerase and controls the expression of numerous genes. Previously, we have reported that posttranslational regulation of σS in the aquatic bacterium Shewanella oneidensis involves the CrsR-CrsA partner-switching regulatory system, but the exact mechanism by which CrsR and CrsA control σS activity is not completely unveiled. Here, using a translational gene fusion, we show that CrsR sequesters and protects σS during the exponential growth phase and thus enables rapid gene activation by σS as soon as the cells enter early stationary phase. We further demonstrate by an in vitro approach that this protection is mediated by the anti-σ domain of CrsR. Structure-based alignments of CsrR orthologs and other anti-σ factors identified a CsrR-specific region characteristic of a new family of anti-σ factors. We found that CrsR is conserved in many aquatic proteobacteria, and most of the time it is associated with CrsA. In conclusion, our results suggest that CsrR-mediated protection of σS during exponential growth enables rapid adaptation of S. oneidensis to changing and stressful growth conditions, and this ability is probably widespread among aquatic proteobacteria.


Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: A meta-analysis.
As for the association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to pediatric asthma, results of published studies yielded conflicts. A systematic review was conducted on the relationship between childhood asthma and VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236). PubMed, Web of Science, CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) database were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated. Overall results suggested that there was a statistically significant association between ApaI polymorphism and childhood asthma in homozygote model (OR = 1.674, 95%CI = 1.269-2.208, P < 0.001) and allele model (OR = 1.221, 95%CI = 1.084-1.375, P = 0.001). Stratification by ethnicity revealed a statistical association in Asians (OR = 1.389, 95%CI = 1.178-1.638, P < 0.001). There was some evidence of an association between BsmI polymorphism and childhood asthma in the homozygote (OR = 1.462, 95%CI = 1.016-2.105, P = 0.041) and allele models (OR = 1.181, 95%CI = 1.006-1.386, P = 0.042). This association reached significance only in the Caucasian group (OR = 1.236, 95%CI = 1.029-1.485, P = 0.023). For FokI, a statistical association was detected in dominant model (OR = 1.281, 95%CI = 1.055-1.555, P = 0.012); this association was significant in allele model (OR = 1.591, 95%CI = 1.052-2.405, P = 0.028) in Caucasian. ApaI polymorphism plays a particular role in childhood asthma in Asians. FokI polymorphism may be connected with pediatric asthma in Caucasian population. And BsmI polymorphism marginally contributes to childhood asthma susceptibility, while there might be no association between TaqI polymorphism and childhood asthma risk. Pediatr Pulmonol. 2017;52:423-429. © 2016 Wiley Periodicals, Inc.


[The elderly and new media].
This article discusses the importance of using new communication technics for the quality of life in old age. Different models of new technics and the consequences for daily life in old age are illustrated. Using new communication technics in old age creates new tasks for gerontology. These scientific and practical tasks are discussed, too.


Subjective cognitive decline and β-amyloid burden predict cognitive change in healthy elderly.
To assess in a longitudinal study whether subjective cognitive decline (SCD) and brain β-amyloid (Aβ) contribute unique information to cognitive decline. One hundred thirty-six healthy elderly from the Berkeley Aging Cohort Study were followed up for a mean of 4 years. SCD and affective measures were generated from the Geriatric Depression Scale (GDS) with factor analysis on data from a larger set of 347 healthy, nondepressed (GDS <11) elderly individuals. Cognition was summarized with previously validated factor scores. Pittsburgh compound B (PiB)-PET scans were acquired to determine the presence (PiB+) or absence (PiB-) of Aβ pathology. Mixed models were used to assess the independent and interactive effects of SCD, affective features, PiB status, and time on cognition, with adjustment for demographic variables. SCD score demonstrated good construct validity compared to an existing measure of subjective memory and was partially explained by several lower-order measurements. Mixed models revealed that SCD interacted with PiB status to predict change in episodic memory and global cognition over time, with adjustment for affective features. PiB+ individuals with more severe SCD demonstrated the steepest cognitive decline. Worse SCD predicted faster decline in working memory independently of PiB status. No such effects were seen for affective scores when adjusted for SCD. PiB+ individuals with SCD are at greatest risk of cognitive decline. Evidence for amyloid alone is not sufficient to indicate risk of rapid cognitive decline in healthy elderly. Effects of GDS on cognitive decline in nondepressed cohorts may be driven by SCD rather than subsyndromal depression.


Trends in recreational walking trail usage in Ireland during the COVID-19 pandemic: Implications for practice.
Despite its potential utility for the outdoor recreation sector, there is no centralised surveillance system for recreational walking trails in Ireland and thus trail usage in Ireland during the COVID-19 pandemic is unknown. This paper aims to report trends in footfall count data on Irish trails during the COVID-19 period and to triangulate findings with openly available mobility data. This descriptive study analysed changes in footfall counts gathered from passive infrared sensors on 33 of Ireland's recreational walking trails between January 2019 and December 2020. The relationship between Google Community Mobility Report (GCMR) data and footfall counts was analysed to corroborate trends in footfall data. Total footfall increased by 6% between 2019 and 2020 on trails included in this analysis. Notably, mean trail usage was between 26% and 47% higher in October-December 2020 than during the same period in 2019. A strong correlation between GCMR data from 'parks' and footfall count data was found. The conclusions of this study are twofold. Firstly, the COVID-19 pandemic increased trail usage in Ireland, especially on trails closer to urban areas and there is potential for this to be a lasting legacy. Secondly, combining multiple data sources can provide trail managers with more detailed representations of trail usage and currently these are not harmonised. Future research should examine ways to encourage sustained recreational walking trail use in new users and implement novel ways to coordinate datasets across systems to monitor visitors on Irish recreational walking trails. This paper presents a number of implications for trail management teams to consider:•Openly available datasets pertaining to mobility, such as Google Community Mobility Reports, can be utilised to corroborate data collected from footfall sensors in place on trails. Furthermore, there may be potential for Google Trends data to help trail management teams gauge interest in specific trails and parks during defined time frames.•There is considerable potential to sustain the COVID-19 legacy of increased trail use, especially for trails closer to urban areas, through promotional campaigns and continued trail maintenance.•There is a need to work across sectors and disciplines within the recreational walking system to identify potential data sources and opportunities for further data collection.


Reporting social behaviours of mixed-species troops formed by Callithrix jacchus and Callithrix penicillata (Primate, Callitrichidae).
In New World primates, mixed-species troops have been reported. Here, we analysed the performance of affiliative and agonistic behaviours of Callithrix jacchus and Callithrix penicillata living in mixed groups. For this purpose, we recorded the interaction of the individuals from two groups located in Bauru city, in the state of São Paulo (Brazil). Our data show that in both groups, affiliative behaviours appeared more frequently than agonistic ones. We concluded that there is cohesion inside the mixed-species troops observed. We suggest that a deeper knowledge about the social behaviour of mixed-species troop species certainly may be useful in projects linked with the management of the impact caused by them.


[Study on TR beta gene mutation in a thyroid hormone resistance syndrome family].
To detect the gene mutation of thyroid hormone receptor beta (TR beta) in a family with thyroid hormone resistance syndrome. The genomic DNA was extracted from peripheral blood leukocytes of the patient, 14 family members and 7 healthy subjects. The exons 7-10 of TR beta gene were amplified by PCR. The products of PCR were purified and sequenced directly to detect the gene mutation. Five members of this family were confirmed to have the C to G transition mutation at nucleotide 1642 site within exon 10 of TR beta gene, which was a missense mutation causing the substitution of Proline to Alanine (P453A); and also to have the C to T transition mutation at nucleotide 1020 within exon 7 of TR beta gene, which was a synonymous mutation that didn't cause the change of amino acid at this position (F245F). The two mutations were heterozygote. No mutation in the exons 7-10 of TR beta gene were identified in other family members. A family with thyroid hormone resistance syndrome caused by TR beta gene mutation is first founded in Chinese people.


A critical review of the function of neuromelanin and an attempt to provide a unified theory.
This paper provides a critical review of the numerous and various biological functions so far attributed to neuromelanin and an attempt to provide a unified theory based on the peculiar physical and chemical properties of the black particle (the neuromelanin cage). It is stressed that neuromelanin is not homogeneous, as is commonly accepted, but is made up of different substrate specific black pigments formed by the oxidation of o.diphenols or other oxygenated precursors (substantia nigra melanin, locus coeruleus melanin, retinal pigmented epithelium or ocular melanin, inner-ear melanin, and so on). Ocular melanin is believed to protect the eye by trapping metals and free radicals. The paper shows that this unconfirmed mechanism is a rather fortuitous irreversible molecular accident, which at times may prove itself deleterious. Albinism often leads to deafness in animals, indicating a genetic correlation. These two conditions appear to be correlated at a molecular level to eye/ear pigmentation and suggest verifying this hypothesis in normal and albino human individuals. Skin and ocular melanin are chemically different. However, they are both involved in light absorption/dissipation. The black particle structure (melanin cage) is believed to be fundamental to this process because there is a common bioelectric mechanism. The latter is worth of further investigation. It is also proposed checking how ocular melanin dissipates the excessive absorbed light (as heat or as current?). It has been claimed that inner-ear melanin mutes acoustic waves. This paper suggests investigating the underlying mechanism and also studying whether this pigment is bio-electrically involved in audiology. According to numerous authors, substantia nigra melanin is only biological garbage. This view is rejected, and it is stressed that intracellular melanogenesis is a fundamental and genetically controlled physiological process. It has been repeatedly claimed that the binding of iron, heavy metals, free radicals and harmful chemicals by substantia nigra melanin is fundamental to body detoxification/protection. Presumably, such irreversible and generic binding mechanisms have no physiological foundation; it is suggested the alternative that, substantia nigra melanin acts as semiconductor, transmitting and modulating nervous impulses, in a reversible way. In fact, substantia nigra melanin is absent or significantly scarce in two conditions of life in which the coordination of movement is either inefficient (newborn babies) or strongly compromised (Parkinson). To check this assumption, further investigation of nucleus caudatus, putamen, globus pallidus, substantia nigra pars compacta and reticulata, nucleus hypothalamicus is recommended.


Adenoid cystic carcinoma in the cavernous sinus diagnosed with the endoscopic endonasal approach.
A 42-year-old woman presented with right oculomotor, abducens, and trigeminal palsy. Neuroimaging revealed a small lesion in the right cavernous sinus mimicking meningioma. Because the symptoms gradually worsened, the patient underwent an endoscopic endonasal transsphenoidal surgery for tumor biopsy. Histological examination of the surgical specimen revealed adenoid cystic carcinoma (ACC). Before and after the operation, no evidence of other primary lesions could be detected. The patient was treated with stereotactic radiosurgery (SRS). ACC in the cavernous sinus can be difficult to diagnosis before histological confirmation, because it is extremely rare as a primary lesion and resembles a cavernous sinus meningioma on neuroimaging studies. Two years after the first SRS, the tumor recurred along the trigeminal nerve and SRS was performed again. Our study illustrates that in case in which a lesion in the cavernous sinus progresses on neurological and neuroimaging studies, a biopsy should be taken to provide most accurate diagnosis and treatment.


A robust reference signal generator for synchronized ventricular assist devices.
Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.


[Severe and recurrent digestive hemorrhage: an uncommon form of colonic schistosomiasis].
Schistosoma mansoni infection is frequent in certain areas of the world in which it is endemic. It is characterised by colonic and hepatic lesions. Gastrointestinal hemorrhages due to rupture of esophageal varices in case of hepatic involvement or moderate rectal bleeding due to colonic involvement may also be observed. We report a case of colonic Schistosoma mansoni infection presenting exclusively with recurrent episodes of serious gastrointestinal hemorrhage without hepatic lesions. All diagnostic investigations were negative. The diagnosis was only established on histological examination of the operative left hemicolectomy carried out with the utmost emergency for the serious recurrent hemorrhage. Histological examination revealed the presence of mucosal micro-ulcers, capillary neovascularization in the submucosa and serosa, and the presence of fibrous nodules and giant cell granulomas surrounding the eggs of Schistosoma mansoni in the serosa. This case is original by its clinical presentation and the difficulty to diagnose the Schistosomiasis.


FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy.
On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.


Clinical application of 13C-Hiolein breath test in assessing pancreatic exocrine insufficiency.
To examine the feasibility and significance of 13C-Hiolein breath test in evaluating chronic pancreatitis-related exocrine insufficiency and efficacy of enzyme treatment. The 13C-Hiolein breath test was used in 8 healthy volunteers (group 1), 8 chronic pancreatitis (CP) patients without steatorrhea (group 2), and 8 CP patients with steatorrhea (group 3). To evaluate the function of pancreatic exocrine, 13CO2 was determined following 13C-Hiolein diet. The 13C-Hiolein test was repeated in group 3 after enzyme supplement therapy. Administration of 13C-Hiolein diet resulted in significantly higher cumulative percent dose of 13C recovery per 6 h (cPDR/6 h) and maximal PDR (PDR(peak)) in the healthy controls (group 1) than the CP patients with steatorrhea (group 3) (11.22%+/-1.22% and 6.11%+/-0.59% vs 2.87%+/-0.73% and 1.53%+/-0.36%, respectively, both P<0.01). In the CP patients with steatorrhea (group 3), a repeated test after enzyme supplementation therapy showed a significant elevation of both cPDR/6 h and PDR(peak) (9.03%+/-0.84% and 2.33%+/-0.47%, both P<0.01 compared with those before enzyme treatment), but cPDR/6 h remained significantly lower than that in the healthy volunteers (group 1, P<0.05). Both cPDR and PDR(peak) in the CP patients without steatorrhea (group 2) were similar to those in the healthy controls (group 1, both P>0.05). The results of 13C-Hiolein breath test well reflect fat metabolism status in CP patients, and the test can be used to monitor the efficacy of pancreatic enzymes therapy.


A clustered-randomized controlled trial of a self-reflection resilience-strengthening intervention and novel mediators.
This study tests the efficacy of a unique resilience-strengthening intervention using a clustered-randomized controlled trial. It was hypothesized that the training, which encourages adaptive self-reflection on stressor events and the effectiveness of coping strategies and resources, would exert a positive effect on mental health outcomes via increased reflection and decreased brooding. The trial was conducted during a significant stressor period with a final sample of 204 second-class Officer Cadets from the Royal Military College, Australia. Platoons of Cadets were randomly allocated to either Self-Reflection Resilience Training (SRT; n = 96) or an exposure-matched active control group that received training as usual (i.e., cognitive-behavioral skill development training) and communication skills seminars (n = 108). Compared to the active control group, SRT was more effective at preventing the onset of depression symptoms and promoting stable levels of perceived stress during a period of increased exposure to training stressors, consistent with a resilient trajectory. The Self-Reflection group unexpectedly demonstrated higher anxiety symptoms than the Control group at immediate follow-up, but these symptoms returned to baseline levels at longer term follow-up. In contrast, the Control group experienced increasing anxiety symptoms between immediate and longer term follow-up. Mediation analyses supported an indirect effect of SRT on all three outcome measures via brooding, but not via reflection. This study provides support for the capacity of a practical, sustainable, and scalable intervention based on self-reflection to strengthen resilience in the military training setting. (PsycInfo Database Record (c) 2021 APA, all rights reserved).