Ungulate use of non-wildlife underpasses.
Wildlife crossing structures can provide safe passage for wildlife across transportation corridors, and can help mitigate the effects of highways and exclusion fencing on wildlife. Due to their costs, wildlife crossing structures are usually installed sparsely and at strategic locations along transportation networks. Alternatively, non-wildlife underpasses (i.e. conventional underpasses for human and domestic animal use) are usually abundant along major infrastructure corridors and could potentially provide safe crossing opportunities for wildlife. To investigate this, we monitored the use of 40 non-wildlife underpasses by roe deer (Capreolus capreolus), and moose (Alces alces) in south-central Sweden. We found that roe deer and moose use non-wildlife underpasses, and prefer underpasses that are at least 11.5 m wide and 5 m tall. Furthermore, roe deer used structures that had little human co-use and were in locations where the forest cover differed on both sides of the highway. In most cases, roe deer and moose were detected within 50 m of the underpass more than they were detected crossing under them. This suggests that animals often approach underpasses without crossing under them, however modifications to underpass design may improve non-wildlife underpass use. We recommend non-wildlife underpasses at gravel and minor roads, particularly those with little human co-use and with variable forest cover on both sides of the highway, be built wider than 11.5 m and taller than 5 m.


A Tailored High-Efficiency Sample Pretreatment Method for Simultaneous Quantification of 10 Classes of Known Endogenous Phytohormones.
One of the hottest topics in plant hormone biology is the crosstalk mechanisms, whereby multiple classes of phytohormones interplay with each other through signaling networks. To better understand the roles of hormonal crosstalks in their complex regulatory networks, it is of high significance to investigate the spatial and temporal distributions of multiple -phytohormones simultaneously from one plant tissue sample. In this study, we develop a high-sensitivity and high-throughput method for the simultaneous quantitative analysis of 44 phytohormone compounds, covering currently known 10 major classes of phytohormones (strigolactones, brassinosteroids, gibberellins, auxin, abscisic acid, jasmonic acid, salicylic acid, cytokinins, ethylene, and polypeptide hormones [e.g., phytosulfokine]) from only 100 mg of plant sample. These compounds were grouped and purified separately with a tailored solid-phase extraction procedure based on their physicochemical properties and then analyzed by LC-MS/MS. The recoveries of our method ranged from 49.6% to 99.9% and the matrix effects from 61.8% to 102.5%, indicating that the overall sample pretreatment design resulted in good purification. The limits of quantitation (LOQs) of our method ranged from 0.06 to 1.29 pg/100 mg fresh weight and its precision was less than 13.4%, indicating high sensitivity and good reproducibility of the method. Tests of our method in different plant matrices demonstrated its wide applicability. Collectively, these advantages will make our method helpful in clarifying the crosstalk networks of phytohormones.


Retrogradely transmitted α-synuclein is taken up by the endophilin-independent endocytosis in the C. elegans neural circuit.
α-Synuclein is a major component of Lewy bodies and Lewy neuritis which are hallmarks of Parkinson's disease, and is known to propagate from cell-to-cell in a prion-like manner. However, the exact mechanism of α-synuclein propagation in cells remains unclear. Despite the increasing number of studies and models of α-synuclein propagation, there is no direct evidence demonstrating whether the propagation is trans-synaptic or synaptic connection-independent, what the direction of propagation is, and what the regulators of α-synuclein propagation are. In this study, we generated a Caenorhabditis elegans model that can help monitoring the neuron-to-neuron propagation of α-synuclein using BiFC system. Using this model, we demonstrated that α-synuclein was propagated into neurons in both anterograde and retrograde manners, with retrograde propagation being dominant. Interestingly, we also found that endophilin, which is a protein required for classical clathrin-mediated endocytic machinery, was not involved in this retrograde propagation. Furthermore, we demonstrated that α-synuclein inhibits neuronal activity through voltage-gated calcium channels. Our findings suggest a possible mechanism for α-synuclein propagation via synapses through a novel uptake pathway.


Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma in the Gastrointestinal Tract in the Modern Era.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) typically arises from sites such as the stomach, where there is no organized lymphoid tissue. Close associations between Helicobacter pylori and gastric MALT lymphoma or Campylobacter jejuni and immunoproliferative small intestinal disease (IPSID) have been established. A subset of tumors is associated with chromosomal rearrangement and/or genetic alterations. This disease often presents as localized disease, requiring diverse treatment approaches, from antibiotic therapy to radiotherapy and immunochemotherapy. Eradication therapy for H. pylori effectively cures gastric MALT lymphoma in most patients. However, treatment strategies for H. pylori-negative gastric MALT lymphoma are still challenging. In addition, the effectiveness of antibiotic therapy has been controversial in intestinal MALT lymphoma, except for IPSID. Endoscopic treatment has been noted to usually achieve complete remission in endoscopically resectable colorectal MALT lymphoma with localized disease. MALT lymphoma has been excluded from post-transplant lymphoproliferative disorders with the exception of Epstein-Barr virus (EBV)-positive marginal zone lymphoma (MZL). We also describe the expanding spectrum of EBV-negative MZL and a close association of the disease with the gastrointestinal tract.


[Practical approach to complex acid-base disorders using a slide rule].
Diagnosis of mixed acid-base disturbances is often difficult. Nowadays it depends on biochemical and statistical interpretation, coupled with clinical data. The acid-base slide-rule is a useful tool to carry out this five step procedure, which it simplifies, giving rapidly at the patient's bed-side an objective support for the diagnosis of acid-base disturbances.


Structural studies of lipophorin in insect blood by differential scanning calorimetry and 13C nuclear magnetic relaxation measurements. Location of hydrocarbons.
The possible structure of lipophorin in insect blood (hemolymph) was investigated by differential scanning calorimetry (DSC) and 13C nuclear magnetic relaxation studies. The DSC heating curves of intact lipophorins showed endothermic peaks between -3 and 40 degrees C for lipophorins which contain hydrocarbons, whereas no such peaks were observed for lipophorins which do not contain this lipid. Hydrocarbon fractions isolated from the lipophorins showed endothermic peaks similar to those obtained from intact lipophorin in terms of the transition temperatures, the shapes, and the enthalpy changes. 13C spin lattice relaxation times of the (CH2)n resonance of hydrocarbons of intact lipophorin were measured as a function of temperature and revealed that the motions of hydrocarbon chains changed coincidentally with the onset and offset of phase transition. These data suggest the presence of a hydrocarbon-rich region within the lipophorin particles.


Perioperative myocardial infarction associated with coronary artery bypass graft surgery: improved sensitivity in the diagnosis within 6 hours after operation with 99mTc-glucoheptonate myocardial imaging and myocardial-specific isoenzymes.
The present study was performed to evaluate scintigraphic imaging with technetium 99m-labeled glucoheptonate and serum enzyme levels of creatine phosphokinase isoenzyme (MB-CPK) in the early diagnosis of perioperative acute myocardial infarction associated with saphenous vein bypass graft operations. Myocardial imaging was done in 27 patients (50% of whom were considered high-risk) before operation and again 5 hours after operation. Four of these patients (15%) had both electrocardiographic and serum MB-CPK evidence of acute myocardial infarction, and all 4 had developed positive postoperative scintigrams. Four other patients had only elevated serum MB-CPK, and scintigrams became positive after operation in 3 of them. In addition, serum MB-CPK 6 hours after operation was 83 +/- 21 mIU/ml (mean +/- standard error of the mean) in patients with positive postoperative scans compared with 24 +/- 5 mIU/ml in those patients with negative postoperative scintigrams (p less than 0.001). Myocardial imaging with 99mTc-glucoheptonate in the perioperative period is rapid, safe, and atraumatic. Furthermore, our results suggest that it is a sensitive method for the early diagnosis of perioperative acute myocardial infarction, and, when imaging is combined with serum MB-CPK isoenzyme analysis, the reliability of the diagnosis of acute myocardial infarction is enhanced even further. Only 1 of the patients who showed perioperative myocardial damage had acute hemodynamic compromise or obvious impairment of recovery in the immediate postoperative period, and the 30-day mortality of the total group was 4% (1 of 27).


A comprehensive clinico-radiological, neuropsychological and biomechanical analysis approach to patients with idiopathic normal pressure hydrocephalus.
A systematic approach to patients with suspected idiopathic normal pressure hydrocephalus (iNPH) is essential to recognize the subset of patients who may benefit from ventriculoperitoneal shunt surgery (VPS). Quantitative biomechanical analysis of gait and balance (QBAGB) may help objectify the response to the cerebrospinal fluid tap test (CSF-TT) and VPS outcome after 3 months and support identification of candidates for VPS. We retrospectively reviewed data from all patients with probable iNPH who 1) underwent clinico-radiological and neuropsychological assessments using validated scales (iNPH Scale and iNPH Radscale) at our centre in the period from January to December 2018; and 2) had completed QBAGB before CSF-TT ('baseline'), shortly after CSF-TT, and at three months after either VPS or conservative treatment. At the time-points 'after CSF-TT' and '3 months', patients with iNPH and VPS (n = 11) significantly improved on the Kiefer Scale score, iNPH Scale total score and gait domain score, as well as in gait velocity and step length measured by QBAGB. In contrast, patients without surgery (n = 10) had unchanged iNPH Scale scores and motor performance throughout. Using data from all patients, we calculated cut-off levels for substantial improvements in gait velocity, step length, and the iNPH Scale domain gait score at the time-point 'after CSF-TT'. QBAGB helps to objectify the response to CSF-TT to select candidates for VPS and corroborates clinico-radiological and neuropsychological data derived from validated scales. The QBAGB cut-off values for substantial improvement after CSF-TT need further elucidation in larger, preferably prospective studies.


Pitch velocity is a predictor of medial elbow distraction forces in the uninjured high school-aged baseball pitcher.
Medial elbow injuries are common among baseball pitchers. Easily accessed methods to assess medial elbow stress may be useful in identifying individuals with increased injury risk. Pitch velocity (PV) is positively associated with higher medial elbow adduction moments. Cohort study; Level of evidence, 2. Participants included 26 uninjured high school pitchers, 15 to 18 years in age. Three-dimensional data and PV were collected as athletes threw 10 fastballs for strikes to a regulation-distance target. Variables of interest were the normalized peak internal elbow adduction moment and peak PV. Linear regression was performed to evaluate the influence of PV on the adduction moment. For the group, mean PV was 71 mph (range, 58-81 mph), and the adduction moment was 0.558 Nm/Ht × mass (range, 0.378-0.723). PV was positively associated with the adduction moment (P < 0.01, R(2)= 0.373). Talented young pitchers may be more susceptible to elbow injuries as a consequence of a biomechanical coupling between PV and upper extremity joint moments. PV may be measured easily and serve as an indicator of medial elbow stress.


Mechanical criticality of fiber networks at a finite temperature.
At zero temperature, spring networks with connectivity below Maxwell's isostatic threshold undergo a mechanical phase transition from a floppy state at small strains to a rigid state for applied shear strain above a critical strain threshold. Disordered networks in the floppy mechanical regime can be stabilized by entropic effects at finite temperature. We develop a scaling theory for this mechanical phase transition at finite temperature, yielding relationships between various scaling exponents. Using Monte Carlo simulations, we verify these scaling relations and identify anomalous entropic elasticity with sublinear T dependence in the linear elastic regime. While our results are consistent with prior studies of phase behavior near the isostatic point, the present work also makes predictions relevant to the broad class of disordered thermal semiflexible polymer networks for which the connectivity generally lies far below the isostatic threshold.


Xenon inhibits excitatory but not inhibitory transmission in rat spinal cord dorsal horn neurons.
The molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method. In vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist. Xenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon.


Signalling pathway of goldfish melanin-concentrating hormone receptors 1 and 2.
Melanin-concentrating hormone (MCH) is the natural ligand for the MCH-1 receptor (MCHR1) and MCH-2 receptor (MCHR2). The MCH-MCHR1 system plays a central role in energy metabolism in rodents. Recently, we identified MCHR1 and MCHR2 orthologues in goldfish, designated gfMCHR1 and gfMCHR2. In a mammalian cell-based assay, calcium mobilization was evoked by gfMCHR2 via both Gαi/o and Gαq, while the gfMCHR1-mediated response was exclusively dependent on Gαq. This coupling capacity to G proteins is in contrast to human MCHR1 and MCHR2. Here, we extended our previous characterization of the two gfMCHRs by examining their different signalling pathway. We found that MCH caused activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) via both gfMCHR1 and gfMCHR2 in dose-dependent manners. Unlike the case for gfMCHR2, gfMCHR1 signalling was not sensitive to pertussis toxin, suggesting Gαq coupling of gfMCHR1 in the ERK1/2 pathway as well as a calcium mobilization system. Cyclic AMP assays revealed that gfMCHR2 was efficiently coupled to Gαi/o, while gfMCHR1 was weakly coupled to Gαs. Finally, we investigated the transduction features stimulated by two mammalian MCH analogues. As expected, Compound 15, which is a full agonist of human MCHR1, was a potent gfMCHR1 agonist in multiple signalling pathways. On the other hand, Compound 30, which is a human MCHR1-selective antagonist with negligible agonist potency, unexpectedly acted as a selective agonist of gfMCHR1. These results are the first to demonstrate that gfMCHR1 and gfMCHR2 have quite different signalling properties from human MCHRs.


Predictors of adverse perinatal outcomes in fetal growth restriction using a combination of maternal clinical factors and simple ultrasound parameters.
To identify predictors of adverse perinatal outcomes in pregnancies with fetal growth restriction (FGR) using a combination of maternal clinical factors and simple ultrasound parameters and develop a risk-scoring model for predicting adverse perinatal outcomes. A retrospective study of 370 non-anomalous singleton pregnancies with FGR was conducted. Multivariate logistic regression analysis was used to identify factors associated with adverse perinatal outcomes; P < 0.05 was considered statistically significant. The discriminative ability was measured with the area under the receiver operating characteristic curve (AUC). A weighted score for each predictor was calculated. Adverse perinatal outcomes occurred in 165/370 (44.6%) cases. There were eight predictive factors, including a history of pregnancy-induced hypertension (PIH) (score = 1), chronic hypertension (score = 3), PIH (score = 2), maternal weight gain less than 8 kg (score = 1), early-onset FGR (score = 1), estimated fetal weight less than 5th percentile (score = 2), amniotic fluid index less than 5 cm (score = 3), and abnormal umbilical artery Doppler (score = 2), with total scores ranging from 0 to 15. AUC for the eight-item predictive model was 0.799 (95% confidence interval 0.753-0.845). A combination of maternal clinical factors and simple ultrasound parameters showed acceptable predictive performance for adverse perinatal outcomes in FGR.


Analysis of zeins' ER retention in Xenopus oocytes.
Zeins, maize storage proteins, are retained in the endoplasmic reticulum (ER) during the intracellular protein targeting process. Hydrophobic interaction has been postulated as the driving force of zeins' aggregation and retention in the ER. Recently, a class of zein (the 27K zein) has been proposed to facilitate zeins' ER retention by anchoring to the ER membrane. This study investigated the significance of the two proposed mechanisms toward zeins' ER retention using Xenopus oocyte. Following injection of the total or 27K zein mRNA, zein's movement within the ER was analyzed based upon the extent of diffusion to the non-injected oocyte half. This study indicates that the total zeins freely move within the lumen of the ER, thus, suggesting that the intermolecular aggregation, leading to insolubility and exclusion from the ER lumenal fluid, may not be essential for zeins' ER retention. This study also suggests that the 27K zein may not facilitate zeins' ER retention by virtue of an anchor to the ER membrane based on its free movement in the ER. Free movement of the total and 27K zeins, under conditions where zein aggregates should form, necessitates a reevaluation of the mechanisms responsible for zein polypeptides' ER retention and protein body formation.


Evaluating the spatial and temporal variations of aquatic weeds (Biomass) on Lower Volta River using multi-sensor Landsat Images and machine learning.
Aquatic invasive weeds affect hydrological, ecological, and socio-economic activities on freshwater ecosystems. On the Lower Volta River (LVR) of Ghana, invasive aquatic weeds have been known to be nuisance to fishing, navigation, aquaculture, hydropower production and other agricultural practices in the area. While information on the spatial and temporal distribution of aquatic weeds would be beneficial in improving weed management and control measures on the river, such information is very scanty. Also, these aquatic weeds are also biomass resources, that can be transformed to bioenergy. Thus, this study evaluated the spatial and temporal variations of aquatic weeds on the Lower Volta River, and assessed their potential biomass for bioenergy production. Random Forest (RF) algorithm and Landsat images were used to map the distribution of the weeds in 1975, 2003, and 2020, respectively. Accuracy assessment results showed mean Overall Accuracy (OA) of 83.44% and mean User Accuracy (UA) of 79.24%. The results indicated that as of 1975, aquatic weeds covered only 1495 ha and appeared in some specific locations such as Kpong and Ada. However, by 2003, the weeds had spread to most parts of the river covering 5600 ha, which was an increase of approximately 4-fold within a period of 28 years. The area covered by the weeds, however declined by 1505 ha between 2003 and 2020. Thus, in 2020, water hyacinth covered about 36% of the aquatic weeds relative to 28% in 2003. The results showed that, the quantity of the water hyacinth biomass per unit area was 21.5 kg/m2. This result can also be used as the basis for resource assessment as well as determination of its viability for bioenergy production and strategies for its modern utilisation. The conversion of water hyacinth into bioenergy remains one of the best aquatic weed management strategies that must be adopted in LVR.


Comprehensive codon usage analysis of porcine deltacoronavirus.
Porcine deltacoronavirus (PDCoV) is a newly identified coronavirus of pigs that was first reported in Hong Kong in 2012. Since then, many PDCoV isolates have been identified worldwide. In this study, we analyzed the codon usage pattern of the S gene using complete coding sequences and complete PDCoV genomes to gain a deeper understanding of their genetic relationships and evolutionary history. We found that during evolution three groups evolved with a relatively low codon usage bias (effective number of codons (ENC) of 52). The factors driving bias were complex. However, the primary element influencing the codon bias of PDCoVs was natural selection. Our results revealed that different natural environments may have a significant impact on the genetic characteristics of the strains. In the future, more epidemiological surveys are required to examine the factors that resulted in the emergence and outbreak of this virus.


Impact of the Poor Oral Health Status of Children on Their Families: An Analytical Cross-Sectional Study.
The impact of poor oral health may not just be limited to the children themselves but can impact their families. The current study aims to perform psychometric analyses of the Arabic version of the Family Impact Scale and investigate the association of its domains with the oral health status of children. This cross-sectional study was carried out in a sample of 500 parent-child dyads from high schools of Jazan city of the Kingdom of Saudi Arabia. The Arabic version of the Family Impact Scale was subjected to reliability and validity tests. The explanatory variables in the current study are: the oral health status, parents combined income, parents' education, age and sex of the child. The descriptive analysis was reported using proportions, this was followed by the bivariate and multivariable analyses. About 24.2% of children were reported to have fair, poor, and very poor oral health. A lower frequency of family impact corresponded with better oral health (OH) status of children (p < 0.001). The likelihood of parent's taking time off from work and having financial difficulties was nearly two-times greater if their children had poor oral health. Similarly, interruption in sleep and other normal activities of parents is four times and five times greater, respectively, if the child has poor oral health status. Thus, the poor oral health of school children in the Jazan region of Saudi Arabia is a matter of grave concern as it is observed to be associated with family impacts; particularly affecting the parent's work, sleep, and other normal family activities.


Volumetric evaluation of fat in the renal sinus in normal subjects using stereological method on computed tomography images and its relationship with body composition.
The aim of the study was: to describe a simple, accurate and practical technique for estimating the volume of adipose tissue within the renal sinus (RS) using stereological method on computed tomography (CT) images; to establish a population database for volume of fat within the RS from 21 to 80 years of age; to investigate the effect of age, gender, body mass index (BMI) and abdominal diameters on RS fat volume in normal subjects. We retrospectively reviewed abdominal CT examinations of 240 patients without renal pathology between the ages of 21 and 80 years. There were 6 groups of patients, with 40 patients for each decade. RS fat volumes in the left and right kidney were 5.70 ± 2.87 cm³ and 4.15 ± 2.39 cm³, respectively, in males and 3.51 ± 2.67 cm³ and 2.49 ± 2.16 cm³, respectively, in females. RS fat volume and age were positively correlated for both kidneys (left: r = 0.46; right: r = 0.44; p < 0.001, both), though it appeared to decline after age 70. Quantitative data may allow clinicians to better estimate the age-related RS fat volume changes and help them in decision making.


Preparation of camptothecin micelles self-assembled from disodium glycyrrhizin and tannic acid with enhanced antitumor activity.
Natural compounds as carriers for hydrophobic drugs have been increasingly used in drug delivery systems. In this study, disodium glycyrrhizin (Na2GA), tannic acid (TA) and camptothecin (CPT) were firstly used to prepare the camptothecin solid dispersion (CPT SD). When dissolved in a solution medium, Na2GA self-assembled to form micelles and CPT was encapsulated in micelles, meanwhile, TA connected with Na2GA through hydrogen bonds to form a contract shell. The average diameter of the CPT-loaded micelles is 80 nm with the critical micellar concentration of 0.303 mg/mL, the zeta potential of -33 mV, the PDI of 0.25 and drug loading 6.22%. In vitro experiments confirmed that the drug-loaded micelles exhibited excellent stability and permeability in the intestinal environment. Furthermore, the formulation showed excellent anti-tumor activity in vitro and in vivo. These findings imply that this nano-micelles provide a more potential and efficacious oral drug formulation for chemotherapy.


The relationship between pressure injury complication and mortality risk of older patients in follow-up: A systematic review and meta-analysis.
Pressure injuries (PIs) have now become a common complication of the elderly patients. Some studies have observed that pressure injuries may increase mortality, but this area of evidence has not been evaluated and summarised. The aim of this study was to compare the mortality of patients with pressure injuries and those without pressure injuries. A meta-analysis of observational studies was performed. PubMed, Cochrane Library, Embase, and Web of Science were searched up to April 2019. Studies about mortality among the elderly patients with and without pressure injuries were included. Methodological quality was assessed by the Newcastle-Ottawa Scale (NOS). The fixed effect or random effect model was determined by the test of heterogeneity. The subgroup analysis was performed based on the pressure injuries stages, the region, and the type of study design. The meta-regression analysis was performed to investigate the relationship between the mortality and patients' enrolled year, average age, the incidence of pressure injuries, and gender ratio. The sensitivity analysis was used to explore the impact of an individual study by excluding one at a time. The hazard ratio (HR) and 95% confidence intervals (CIs) in terms of the comparison of two groups were extracted for meta-analysis. A survival curve between two groups by individual patient-level was drew. Eight studies with 5523 elderly patients were included in the analysis. Follow-up periods for the included studies ranged from about 0.5 to 3 years. The elderly patients who complicated with pressure injuries had a higher risk of death. The pooled HR was 1.78 (95% CI 1.46-2.16). A funnel plot showed no publication bias. Further subgroup analysis showed that HR values for the patient stage 3 to 4 pressure injuries (HR:2.41; 95% CI:1.08-5.37) were higher than stage 1-4 and 2-4 pressure injuries (HR: 1.66; 95% CI: 1.35-2.05; HR: 1.74; 95% CI: 1.16-2.60). The meta-regression analysis found that patients' enrolled year, average age, the incidence of pressure injuries, and gender ratio were not the sources of heterogeneity. Sensitivity analyses showed that the outcomes of the study did not change after removing the Onder's article. The survival curve at the individual patient-level also indicated that patients complicated with pressure injuries significantly increased the risk of death (HR: 1.958; 95% CI: 1.79-2.14) in elderly patients. Our meta-analysis indicated that patients complicated with pressure injuries are estimated to have a two times higher risk on mortality compared with patients without pressure injuries during the 3 years follow-up period. Particular attention should be given to the elderly patients who are at higher risk for mortality.


Towards a CRISPeR understanding of homologous recombination with high-throughput functional genomics.
CRISPR-dependent genome editing enables the study of genes and mutations on a large scale. Here we review CRISPR-based functional genomics technologies that generate gene knockouts and single nucleotide variants (SNVs) and discuss how their use has provided new important insights into the function of homologous recombination (HR) genes. In particular, we highlight discoveries from CRISPR screens that have contributed to define the response to PARP inhibition in cells deficient for the HR genes BRCA1 and BRCA2, uncover genes whose loss causes synthetic lethality in combination with BRCA1/2 deficiency, and characterize the function of BRCA1/2 SNVs of uncertain clinical significance. Further use of these approaches, combined with next-generation CRISPR-based technologies, will aid to dissect the genetic network of the HR pathway, define the impact of HR mutations on cancer etiology and treatment, and develop novel targeted therapies for HR-deficient tumors.


Spinal Locomotion in Cats Following Spinal Cord Injury: A Prospective Study.
This article aimed to evaluate the safety and efficacy of intensive neurorehabilitation in paraplegic cats, with no deep pain perception (grade 0 on the modified Frankel scale), with more than three months of injury. Nine cats, admitted to the Arrábida Veterinary Hospital/Arrábida Animal Rehabilitation Center (CRAA), were subjected to a 12-week intensive functional neurorehabilitation protocol, based on ground and underwater treadmill locomotor training, electrostimulation, and kinesiotherapy exercises, aiming to obtain a faster recovery to ambulation and a modulated locomotor pattern of flexion/extension. Of the nine cats that were admitted in this study, 56% (n = 5) recovered from ambulation, 44% of which (4/9) did so through functional spinal locomotion by reflexes, while one achieved this through the recovery of deep pain perception. These results suggest that intensive neurorehabilitation can play an important role in ambulation recovery, allowing for a better quality of life and well-being, which may lead to a reduction in the number of euthanasia procedures performed on paraplegic animals.


Three-dimensional orientation of the femoral curvature. How well does it match with the sagittal curvature of femoral implants?
The curvature of the femoral shaft is generally considered as residing in the sagittal plane. While many studies have measured the femur's radius of curvature, very few have studied the orientation of the plane in which it resides. The orientation of this plane may affect the rotation of intramedullary nails or revision stems with diaphyseal locking. This led us to conduct a three-dimensional (3D) anatomical study to: 1) analyze the 3D curvature of the femoral diaphysis by specifying the orientation of the plane in which it resides, 2) look for relationships between the curvature's orientation and anatomical parameters of the femur. We hypothesized that the femoral curvature resides in the anterolateral plane, not the sagittal plane. A computed tomography scan was performed on 45 dry femur bones provided by a cadaver laboratory. The 3D reconstructions were analyzed to characterize the curvature of the diaphyseal shaft, radius of its various portions and to determine the plane in which it resides relative to the standard coronal reference plane defined by three points: posterior side of both condyles and the greater trochanter. The following parameters were measured: length, neck-shaft angle, femoral valgus (between anatomical and mechanical axis) and neck anteversion. The largest curvature was in a plane oriented on average of 78.3°±14.9° (35.2° to 106.7°) anterolateral. The correlation between femoral curvature and neck-shaft angle (R=0.172), size (R=0.095), valgus (R=0.104) and overall curvature (R=0.60) was low. Implants with diaphyseal fixation are designed such that the femoral curvature resides in a strict sagittal plane. Long revision stems with diaphyseal fixation may have a tendency to rotate laterally (externally) during insertion. Correcting this external rotation to prevent anteversion may result in a less than satisfactory press-fit. The femoral curvature must be taken into account when designing intramedullary implants. IV, Cadaver study without control group.


Micro scale. Rapid and simple determination of tegafur (FT) by high pressure liquid chromatography in plasma.
A high-pressure liquid chromatographic (HPLC) method was developed for the assay of tegafur in small plasma samples of each mice using chlorouracil as the internal standard and reversed phase microparticle column. This method without any special separation and purification techniques is micro scale and simpler, more rapid and precise for the determination of tegafur in plasma of small animal than that desirable.


Is research on borderline personality disorder underfunded by the National Institute of Health?
The relationship between bipolar disorder and borderline personality disorder has generated intense interest. Similar to patients with bipolar disorder, patients with borderline personality disorder are frequently hospitalized, are chronically unemployed, abuse substances, attempt and commit suicide. However, one significant difference between the two disorders is that patients with borderline personality disorder are often viewed negatively by mental health professionals. In the present paper we examined whether this negative bias against borderline personality disorder might be reflected in the level of research funding on the disorder. We searched the National Institute of Health (NIH) Research Portfolio Online Portfolio Reporting Tool (RePORT) for the past 25 years and compared the number of grants funded and the total amount of funding for borderline personality disorder and bipolar disorder. The yearly mean number of grants receiving funding was significantly higher for bipolar disorder than for borderline personality disorder. Results were the same when focusing on newly funded grants. For every year since 1990 more grants were funded for bipolar disorder than borderline personality disorder. Summed across all 25 years, the level of funding for bipolar disorder was more than 10 times greater than the level of funding for borderline personality disorder ($622 million vs. $55 million). These findings suggest that the level of NIH research funding for borderline personality disorder is not commensurate with the level of psychosocial morbidity, mortality, and health expenditures associated with the disorder.


Quantitative analysis of the spatial distribution of ultrastructural differentiation markers during development ofDictyostelium discoideum.
The appearance and spatial distrubution of ultrastructural markers ofDictyostelium discoideum differentiation were quantitatively analysed. Our results combined with data from the literature on the functions of cells at various stages of development lead to the following conclusions. When food is no longer available all amoebae initially develop an autophagic apparatus in order to sustain metabolism. After slugs have been formed, autophagy is suppressed in the prespore cells. During aggregation a number of cells gradually form prespore characteristics. These cells arise at random but later they become located in the basal part of the tip-forming aggregate. From the early slug stage onwards, cells of the posterior two third region gradually enter into the prespore pathway. During prolonged slug migration the optimal acquirement of prespore characteristics is blocked. Cells of the anterior region show no active differentiation but they maintain the morphology and most of the functions of aggregating cells. At the rear-guard of the slug and later on in the basal region of the maturing fruiting body, a second anteriorlike region appears. Actual stalk cell differentiation takes place only at the apex and at the base of the developing fruiting body.


Extent of transverse sinus stenosis does not predict visual outcomes in idiopathic intracranial hypertension.
We aimed to investigate whether the degree of transverse sinus stenosis (TSS) on magnetic resonance venography (MRV) can predict visual outcomes in patients with idiopathic intracranial hypertension (IIH). A chart review identified IIH patients followed for at least 6 months. Mean deviation (MD) on visual field (VF) testing at initial and last follow-up visits, best corrected visual acuity (BCVA), patients' age, body mass index, and lumbar puncture opening pressure were recorded. MRV was used to grade TSS on a scale of 0-8 using the grading scheme proposed by Farb et al., whereby a lower score indicates a greater degree of stenosis. Linear regression analysis was used to test for association between above variables and MD on VF, including change in MD over time. 44 female patients were followed for a median of 26 months. All patients had unilateral or bilateral TSS on MRV. The median TSS score was 3/8. The median BCVA was 0.06 logMAR at baseline. The median VF MD was -3.02 dB at baseline and -1.96 dB at final follow-up. There was no significant association between the degree of TSS and either baseline MD (P-value = 0.34) or the change in MD on VF over the course of follow-up (P-value = 0.54). Baseline BCVA (P = 0.045) and baseline MD (P < 0.001) were the only significant predictors of changes in MD on VF over follow-up. Baseline BCVA and MD on VF were the only significant predictors of visual outcome in IIH patients. While all patients demonstrated TSS on MRV, the degree of TSS did not correlate with visual prognosis.


Overestimation of genetic risks owing to small sample sizes in cardiovascular studies.
We sought evidence of publication bias to explain conflicting findings in studies of angiotensin-converting enzyme deletion polymorphism (ACE D) and glycoprotein IIIa PlA2 (PLA2) polymorphism and the risk of myocardial infarction. Factor 5 Leiden (F5L), a well-established thrombotic risk factor, served as an internal comparison. We conducted systematic reviews of published studies involving ACE D, PLA2, F5L and relevant outcomes, searching medline (January 1990 through February, 2001), bibliographies, and meta-analyses. Random effects pooled odds ratios (95% confidence interval) for cardiovascular outcomes were as follows: PLA2 (n = 13,167 subjects): 1.13 (1.02, 1.26); ACE D (n = 42,140 subjects): 1.22 (1.11, 1.35); and F5L (n = 27,277 subjects): 4.43 (3.65, 5.38). However, funnel plots of ACE D and PLA2, but not F5L, showed an inverse relationship between sample size and odds ratios for ACE D (p = 0.02) and PLA2 (p = 0.04) but not F5L (p = 0.65) by Egger's test for potential publication bias. Despite research-based genotyping of over 50,000 subjects, the overall risk for myocardial infarction as a result of PLA2 and ACE D remains doubtful. Our study provides a clear example of how publication of underpowered studies can spuriously implicate polymorphisms as genetic risk factors.


5-Chloro-3-cyclo-hexyl-sulfonyl-2-methyl-1-benzofuran.
In the title compound, C(15)H(17)ClO(3)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, mol-ecules are linked through weak inter-molecular C-H⋯O and C-H⋯π inter-actions.


Noise-induced scaling in skull suture interdigitation.
Sutures, the thin, soft tissue between skull bones, serve as the major craniofacial growth centers during postnatal development. In a newborn skull, the sutures are straight; however, as the skull develops, the sutures wind dynamically to form an interdigitation pattern. Moreover, the final winding pattern had been shown to have fractal characteristics. Although various molecules involved in suture development have been identified, the mechanism underlying the pattern formation remains unknown. In a previous study, we reproduced the formation of the interdigitation pattern in a mathematical model combining an interface equation and a convolution kernel. However, the generated pattern had a specific characteristic length, and the model was unable to produce a fractal structure with the model. In the present study, we focused on the anterior part of the sagittal suture and formulated a new mathematical model with time-space-dependent noise that was able to generate the fractal structure. We reduced our previous model to represent the linear dynamics of the centerline of the suture tissue and included a time-space-dependent noise term. We showed theoretically that the final pattern from the model follows a scaling law due to the scaling of the dispersion relation in the full model, which we confirmed numerically. Furthermore, we observed experimentally that stochastic fluctuation of the osteogenic signal exists in the developing skull, and found that actual suture patterns followed a scaling law similar to that of the theoretical prediction.


LncRNA PVT1 up-regulation is a poor prognosticator and serves as a therapeutic target in esophageal adenocarcinoma.
PVT1 has emerged as an oncogene in many tumor types. However, its role in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) is unknown. The aim of this study was to assess the role of PVT1 in BE/EAC progression and uncover its therapeutic value against EAC. PVT1 expression was assessed by qPCR in normal, BE, and EAC tissues and statistical analysis was performed to determine the association of PVT1 expression and EAC (stage, metastases, and survival). PVT1 antisense oligonucleotides (ASOs) were tested for their antitumor activity in vitro and in vivo. PVT1 expression was up-regulated in EACs compared with paired BEs, and normal esophageal tissues. High expression of PVT1 was associated with poor differentiation, lymph node metastases, and shorter survival. Effective knockdown of PVT1 in EAC cells using PVT1 ASOs resulted in decreased cell proliferation, invasion, colony formation, tumor sphere formation, and reduced proportion of ALDH1A1+ cells. Mechanistically, we discovered mutual regulation of PVT1 and YAP1 in EAC cells. Inhibition of PVT1 by PVT1 ASOs suppressed YAP1 expression through increased phosphor-LATS1and phosphor-YAP1 while knockout of YAP1 in EAC cells significantly suppressed PVT1 levels indicating a positive regulation of PVT1 by YAP1. Most importantly, we found that targeting both PVT1 and YAP1 using their specific ASOs led to better antitumor activity in vitro and in vivo. Our results provide strong evidence that PVT1 confers an aggressive phenotype to EAC and is a poor prognosticator. Combined targeting of PVT1 and YAP1 provided the highest therapeutic index and represents a novel therapeutic strategy.


Melanocytoma of the foramen magnum.
This report concerns a 66-year-old man with a melanocytoma arising at the foramen magnum. Magnetic resonance imaging disclosed a well-circumscribed tumor extending from the medulla oblongata to C1 with gadolinium enhancement. A heavily pigmented tumor located under the leptomeninges was removed surgically. Although the patient died 8 months later of renal cell carcinoma, no recurrence or metastasis of the melanocytoma was detected by radiographic examination. Microscopically, the resected tumor was composed of polygonal to spindle-shaped cells containing large amounts of melanin. The bland nuclei of the tumor cells were of uniform size. No mitotic figures were seen. The tumor cells were positively immunostained for S-100 protein and by antibody HMB-45. They were not stained using the Ki-67 (MIB-1) antibody, indicating low proliferative activity. The ultrastructural examination revealed numerous mature melanosomes and basal laminae surrounding nests of cells. The tumor was diagnosed as a melanocytoma on the bases of its microscopic features and the lack of Ki-67 immunoreactivity. The ultrastructural and immunohistochemical features of melanocytomas are distinct from those of meningiomas. It is likely that melanocytomas and melanotic schwannomas represent opposite extremes of the continuous spectrum of neuroectodermal tumors derived from the neural crest.


Self-organizing molecular field analysis on human β-secretase nonpeptide inhibitors: 5, 5-disubstituted aminohydantoins.
5, 5-disubstituted aminohydantoins have been recently reported as potent and selective human β-secretase (BACE-1) inhibitors. Self-Organizing Molecular Field Analysis (SOMFA) is used to study the correlation between the molecular properties and biological activities of the 5, 5-disubstituted aminohydantoins inhibitors. Four different alignments and two charge-assigning methods were investigated. The model derived from the superposition of docked conformation with AM1 charge showed satisfied predictive ability, which has good non-cross-validated r(2) (0.842), cross-validated q(2) (0.792), F-test value (254.75) and satisfied predictive ability r(2)(pred) (0.721). Analysis of SOMFA model may provide some useful information in the design of BACE-1 inhibitors with better spectrum of activity.


Introduction of miscarriage bereavement leave in New Zealand in 2021: A comparison with international experiences.
In early 2021, the New Zealand Parliament introduced miscarriage bereavement leave prompting global debate about creating a right to paid time off work for people bereaved through pregnancy loss. Construing such time off as bereavement leave, rather than sick leave or maternity leave, acknowledges the profound significance of the event, but there is limited evidence on whether leave improves mental or physical health outcomes. In this paper we compare four countries with some form of specific bereavement leave for pregnancy losses: New Zealand, United Kingdom, India, and the Phillippines. We also examine an ongoing effort to introduce a similar policy in the USA and the employer-led approach advocated by others. Comparisons are made relating to when during pregnancy leave is available, how much leave is available, how accessible the leave is, what proof of pregnancy loss is required, and who is covered. We conclude by suggesting policy-makers consider a stepped model where there are greater protections for later pregnancy losses and advise advocates to aim to link pregnancy loss bereavement with bereavement leave for other losses.


The asymmetric influence of environmental-related technological innovation on climate change mitigation: what role do FDI and renewable energy play?
This study aims to provide a new perspective on environmental studies by examining the influence of environmental-related technological innovation, foreign direct investment, renewable energy consumption, and economic growth on the climate change index (CCI), a novel proxy for environmental quality indicators. From the econometric standpoint, this study employs the "non-linear autoregressive distributed lag" model and spectral causality over the period of 1999-2018 for India. The results show that positive shocks to economic growth have detrimental long- and short-term effects on environmental quality, whereas negative shocks have no effect. While a positive shock has an insignificant impact, a negative shock to environmental technology innovation has a long-term negative impact on environmental quality. This study provides evidence for the pollution halo hypothesis in India. Besides, a long-term negative shock to the usage of renewable energy fosters environmental degradation. Furthermore, in short-, medium-, and long-term frequency, spectral causality demonstrates unidirectional causation from CCI to environmental-related technological innovation. Bidirectional causation is demonstrated between the CCI and renewable energy consumption in the short and medium term. In addition, environmental-related technological innovation and foreign direct investment are demonstrating a bidirectional relationship in the short term. This study has advocated the Sustainable Development Goals (SDGs)-centric policy paradigm, which can assist the Indian government in achieving SDG-13 (mitigating climate change) and SDG-7 (clean energy consumption).


Methionine-enkephalin in migraine and tension headache. Differences between classic migraine, common migraine and tension headache, and changes during attacks.
We measured methionine-enkephalin (MET) in platelets and platelet-poor-plasma of drug-free patients with classic migraine, common migraine or tension headache (TH). Migraineurs were studied both between and during attacks. TH patients were characterized by low platelet-MET and high plasma-MET levels, whereas migraine patients showed high platelet-MET and reduced plasma-MET levels. During migraine attacks both platelet and plasma-MET concentrations increased considerably. We suggest that determination of MET levels in platelets and plasma may be a useful marker to discriminate between TH and common migraine. The rise in MET during attacks may be directed against the ictal increase of serotonin.


Bacterial colonization of epidural catheters used for short-term postoperative analgesia: microbiological examination and risk factor analysis.
The authors conducted this prospective study to determine the incidence, potential routes, and risk factors of microbial colonization of epidural catheter used for postoperative pain control. Two-hundred five patients with epidural analgesia for postoperative pain were studied. On removal of the catheter, five samples were sent for culture: the infusate, a swab from inside the hub of the epidural catheter connector, a swab from the skin around the catheter insertion site, the subcutaneous segment, and the tip of the catheter. Clinical data related to the catheter insertion, management, and general patient conditions were collected. The positive culture rates for the subcutaneous and tip segments of the catheter were 10.5% and 12.2%, respectively. The most common organism in the culture was coagulase-negative staphylococcus. There was a strong linear relationship between bacterial colonization in the skin around the catheter insertion site and growth from the subcutaneous and tip segments of catheter (P = 0.000). Catheter-related events at ward, blood transfusion, and positive culture from the skin at the insertion site were risk factors for bacterial colonization of epidural catheters. Inflammation at catheter insertion site, catheter indwelling time, and level of catheter insertion were not predicators for epidural catheter colonization. The authors' results suggest that bacterial migration along the epidural catheter track is the most common route of epidural catheter colonization. Maintaining sterile skin around the catheter insertion site will reduce colonization of the epidural catheter tip.


Factors associated with in vitro interferon-gamma production in tuberculosis.
Macrophage activation assisted by interferon-gamma (IFN-γ) is a primary mechanism by which Mycobacterium tuberculosis is killed, but IFN-γ (production is inhibited in tuberculosis (TB) patients. The production of IFN-γ is influenced by many factors, such as interleukin (IL)-10, IL-12, IL-18, and clinical diseases; but the relative importance of each factor is unclear. We evaluated the effects of these factors in 46 healthy individuals, 81 patients with TB, and 88 patients with non-TB pneumonia. The responses of IFN-γ, IL-10, IL-12 and IL-18 were determined from phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs). General linear model analysis showed that disease status and IL-12 response were the independent factors associated with the IFN-γ response. The production of IFN-γ was not affected by IL-10 and IL-18. There was a significant relationship between the IFN-γ response and the IL-12 response among patients with non-TB pneumonia, patients with TB, and healthy participants (Pearson's correlation coefficients of 0.466, 0.483, and 0.464, respectively). Production of IFN-γ in PBMCs was associated with active pulmonary TB and IL-12 response.


Stakeholder position paper: food animal veterinarian.
Food animal veterinarians practice in a variety of settings with considerable differences between the settings. Due to variability, aggregate data from surveillance of antimicrobial use is not very useful to practitioners unless correlated information is provided, such as the relative disease status, ages of animals, and purpose of use. Of greater utility is use data as it relates to a specific farm or production system. Of greater importance to clinical practitioners is a meaningful surveillance system that tracks trends in antimicrobial resistance in common pathogens causing animal diseases.


Developing improved methods for identifying the cost-efficient abatement set in coastal water quality protection.
Eutrophication of coastal waters is a recognised problem in estuaries around the globe. To analyse cross-boundary water quality management, such as protection of the Baltic Sea, economic nutrient abatement models commonly operate on a large scale, grouping river systems to large catchment areas. Theoretical deliberation suggests that modelling abatement in such a way removes the opportunity of targeting measures to the most vulnerable regions within the catchment, while overestimating the capacity of abatement measures in the upstream areas. However, the implications on designing environmental policy depend on catchment characteristics and the stringency of the abatement targets. In this study a model of the catchment area is built with zones that are an increasing distance away from the coast to show what kind of bias in the optimal abatement set is caused by the assumption of spatial homogeneity. By solving the model with and without the zones for good ecological status at the South-West coast of Sweden, it is shown that while assuming homogeneity prevents from perceiving the abatement measures where they would be the most effective, it also leads to ignoring spatial limitations that are more relevant to a subset of abatement measures, such as the wetlands and buffer zones. Following from the relatively large nitrogen abatement targets, the overall effect of assuming catchment homogeneity is to underestimate the abatement costs and to overestimate the potential of wetlands to reduce nitrogen.


The HLA polymorphism and susceptibility to disease.
Remarkable differences were observed when 1,465 healthy Caucasian individuals and 128 healthy Negro individuals were compared for the genetic distribution of 25 different HLA antigens. Caucasians had a significantly higher frequency of A1, A3, B8, and Bw16, and Negroes of A28 and Aw30. The haplotype which had the highest incidence as well as the greatest positive linkage disequilibrium was A1-B8 among Caucasians and A2-B12 among Negroes. Genetic distance between the two races was 0.0592. The 89 Caucasian patients with renal failure did not demonstrate any significant deviations in phenotype frequencies (PF) of various antigens, when compared with healthy Caucasians; however, 48 similar Negro patients had twice as high an incidence of Bw17 as the healthy Negroes. No significant deviation in PF was observed in 77 Caucasian patients who had leukemia; however, 32 Caucasian patients who had back pain (24 also had back stiffness) due to spondylitic, arthritic or disc syndrome, had a significant increase of Bw16 and of B27, and a decrease of B12, when compared to Caucasian controls.


Interferon regulatory factor signaling in autoimmune disease.
Interferon regulatory factors (IRFs) play critical roles in pathogen-induced innate immune responses and the subsequent induction of adaptive immune response. Dysregulation of IRF signaling is therefore thought to contribute to autoimmune disease pathogenesis. Indeed, numerous murine in vivo studies have documented protection from or enhanced susceptibility to particular autoimmune diseases in Irf-deficient mice. What has been lacking, however, is replication of these in vivo observations in primary immune cells from patients with autoimmune disease. These types of studies are essential as the majority of in vivo data support a protective role for IRFs in Irf-deficient mice, yet IRFs are often found to be overexpressed in patient immune cells. A significant body of work is beginning to emerge from both of these areas of study - mouse and human.


The functional analysis of the CHMP2B missense mutation associated with neurodegenerative diseases in the endo-lysosomal pathway.
Endosomal sorting complexes required for transport (ESCRTs) regulate a key sorting step of protein trafficking between endosomal compartments in lysosomal degradation. Interestingly, mutations in charged multivesicular body protein 2B (CHMP2B), which is a core subunit of ESCRT-III, have been identified in some neurodegenerative diseases. However, the cellular pathogenesis resulting from CHMP2B missense mutations is unclear. Furthermore, little is known about their functional analysis in post-mitotic neurons. In order to examine their cellular pathogenesis, we analyzed their effects in the endo-lysosomal pathway in post-mitotic neurons. Interestingly, of the missense mutant proteins, CHMP2B(T104N) mostly accumulated in the Rab5- and Rab7-positive endosomes and caused delayed degradation of EGFR as compared to CHMP2B(WT). Furthermore, CHMP2B(T104N) showed less association with Vps4 ATPase and was avidly associated with Snf7-2, a core component of ESCRT-III, suggesting that it may cause defects in the process of dissociation from ESCRT. Of the missense variants, CHMP2B(T104N) caused prominent accumulation of autophagosomes. However, neuronal cell survival was not dramatically affected by expression of CHMP2B(T104N). These findings suggested that, from among the various missense mutants, CHMP2B(T104N) was associated with relatively mild cellular pathogenesis in post-mitotic neurons. This study provided a better understanding of the cellular pathogenesis of neurodegenerative diseases associated with various missense mutations of CHMP2B as well as endocytic defects.


Microglial GRK2: a novel regulator of transition from acute to chronic pain.
Pain is a hallmark of tissue damage and inflammation promoting tissue protection and thereby contributing to repair. Therefore, transient acute pain is an important feature of the adaptive response to damage. However, in a significant number of cases, pain persists for months to years after the problem that originally caused the pain has resolved. Such chronic pain is maladaptive as it no longer serves a protective aim. Chronic pain is debilitating, both physiologically and psychologically, and treatments to provide relief from chronic pain are often ineffective. The neurobiological mechanisms underlying the transition from adaptive acute pain to maladaptive chronic pain are only partially understood. In this review, we will summarize recent evidence that a kinase known as G protein-coupled receptor kinase (GRK2) is a key regulator of the transition from acute to chronic inflammatory pain. Our recent studies have shown that mice with a reduction in the cellular level of GRK2 develop chronic hyperalgesia in response to inflammatory mediators that induce only transient hyperalgesia in WT mice. This finding is clinically relevant because rodent models of chronic pain are associated with reduced cellular levels of GRK2. We propose that GRK2 is a newly discovered major player in the regulation of chronic pain. The pathways regulated by this kinase may open up new avenues for development of treatment strategies that target the cause, and not the symptoms of chronic pain.


Possible application of stable isotope compositions for the identification of metal sources in soil.
Metals in soil are potentially harmful to humans and ecosystems. Stable isotope measurement may provide "fingerprint" information on the sources of metals. In light of the rapid progress in this emerging field, we present a state-of-the-art overview of how useful stable isotopes are in soil metal source identification. Distinct isotope signals in different sources are the key prerequisites for source apportionment. In this context, Zn and Cd isotopes are particularly helpful for the identification of combustion-related industrial sources, since high-temperature evaporation-condensation would largely fractionate the isotopes of both elements. The mass-independent fractionation of Hg isotopes during photochemical reactions allows for the identification of atmospheric sources. However, compared with traditionally used Sr and Pb isotopes for source tracking whose variations are due to the radiogenic processes, the biogeochemical low-temperature fractionation of Cr, Cu, Zn, Cd, Hg and Tl isotopes renders much uncertainty, since large intra-source variations may overlap the distinct signatures of inter-source variations (i.e., blur the source signals). Stable isotope signatures of non-metallic elements can also aid in source identification in an indirect way. In fact, the soils are often contaminated with different elements. In this case, a combination of stable isotope analysis with mineralogical or statistical approaches would provide more accurate results. Furthermore, isotope-based source identification will also be helpful for comprehending the temporal changes of metal accumulation in soil systems.


Cloning and characterization of the glycine-cleavage enzyme system of Escherichia coli.
The glycine-cleavage enzyme system of Escherichia coli has been cloned in the cosmid vector pMF7. The recombinant plasmid, designated pGS64, carries two 19.4-kb EcoRI insert fragments. One of these fragments, which carries the gcv system, was subcloned from plasmid pGS64 into the plasmid vectors pACYC184 and pSC101 (creating plasmids pGS96 and pGS97, respectively). Plasmid pGS97, but not pGS96, complements a gcv mutant on glycine-supplemented plates. Enzyme assays, however, verified that both plasmids carry an inducible gcv system. The location of the gcv system in plasmid pGS97 was determined by Tn5 insertional inactivation. Subcloning experiments identified the region on the 19.4-kb fragment that inhibits growth in strains transformed with plasmid pGS96 and a region that is possibly involved in negative regulation of the gcv system.


Failed surgical ligation of the proximal left subclavian artery during hybrid thoracic endovascular aortic repair successfully managed by percutaneous plug or coil occlusion: a report of 3 cases.
Open surgical rerouting and proximal ligation of one or more supra-aortic vessels prior to endovascular stent-graft placement has become an alternative to major open thoracic surgery in the treatment of complex thoracic aortic disease. Complications owing to failed surgical ligation of the left subclavian artery are rare. In this report, 3 cases of failed ligation are presented. Diagnosis was made by CT-scan and treatment was performed by transcatheter coil and plug embolization, avoiding redo neck surgery.


Induction of parasite antigen-specific antibody responses in unsensitized human B cells is dependent on the presence of cytokines after T cell priming.
Using two recombinant filarial protein Ags and keyhole limpet hemocyanin, we sensitized T cells from uninfected, nonatopic individuals in such a manner that they were able to provide help for the selective induction of an Ag-specific Ab response. IL-2 and IL-4 were shown to be critical for sensitizing the T cells; once sensitized, these T cells could provide the necessary signals for B cells to produce Ag-specific Abs, provided that IL-4 (or IL-2) was supplied exogenously. Primary exposure of T cells to IFN-gamma, but not to IL-12, prevented the Ag-sensitized T cells from helping B cells to produce specific Abs, apart from the IgG2 isotype. These data suggest that Ab-producing B cells of a defined Ag specificity and isotype can be generated differentially after in vitro priming of human T cells by Ag, providing regulatory cytokines are also present.


VT ablation based on CT imaging substrate visualization: results from a large cohort of ischemic and non-ischemic cardiomyopathy patients.
The eradication of ventricular tachycardia (VT) isthmus sites constitutes the minimal procedural endpoint for VT ablation procedures. Contemporary high-resolution computed tomography (CT) imaging, in combination with computer-assisted analysis and segmentation of CT data, facilitates targeted elimination of VT isthmi. In this context, inHEART offers digitally rendered three-dimensional (3D) cardiac models which allow preoperative planning for VT ablations in ischemic and non-ischemic cardiomyopathies. To date, almost no data have been collected to compare the outcomes of VT ablations utilizing inHEART with those of traditional ablation approaches. The presented data are derived from a retrospective analysis of n = 108 patients, with one cohort undergoing VT ablation aided by late-enhancement CT and subsequent analysis and segmentation by inHEART, while the other cohort received ablation through conventional methods like substrate mapping and activation mapping. The ablations were executed utilizing a 3D mapping system (Carto3), with the mapping generated via the CARTO® PENTARAY™ NAV catheter and subsequently merged with the inHEART model, if available. Results showed more successful outcome of ablations for the inHEART group with lower VT recurrence (27% vs. 42%, p < 0.06). Subsequent analyses revealed that patients with ischemic cardiomyopathies appeared to derive a significant benefit from inHEART-assisted VT ablation procedures, with a higher rate of successful ablation (p = 0.05). Our findings indicate that inHEART-guided ablation is associated with reduced VT recurrence compared to conventional procedures. This suggests that employing advanced imaging and computational modeling in VT ablation may be valuable for VT recurrences.


[Frequency of chest X-ray suggestive of SARS-CoV-2 involvement from March to May 2020 in the population of an urban health area].
Know the number and percentage of chest X-rays (CXR) referred to a Primary Care Imaging Center and Primary Care Emergency Center to rule out lung involvement due to SARS-CoV-2 from March 16 to May 15, 2020, in an urban health area of about 400,000 reference population inhabitants. To determine the percentage of cases suggestive of pulmonary involvement due to SARS-CoV-2 CXR and the percentage of cases without pulmonary involvement of the total CXR derived in the reference population from March 16 to May 15, 2020. Design observational descriptive study. The radiological criteria to classify probable pulmonary infection by SARS-CoV-2 (RxT[+]) are: 1) focal opacity; 2) faint focal opacity; 3) faint diffuse increase in density; 4) focal or diffuse interstitial pattern, and 5) focal or diffuse interstitial alveolus pattern. Maintain CXR as a useful screening method in the middle stages of the disease, when CXR is more sensitive to detect lung involvement due to SARS-CoV-2. Our graph of affectation by SARS-CoV-2 does not present assessable differences with the expected curve in an epidemic.


Comparative study of hollow-fiber liquid-phase micro-extraction and an aqueous two-phase system for determination of phytohormones in soil.
Two methods, hollow-fiber liquid-phase micro-extraction (HF-LPME) and an aqueous two-phase system (ATPS), have been systematically optimized and compared for extraction and determination of phytohormones in soil by high-performance liquid chromatography (HPLC). The effects on extraction of conditions including solvent type and volume, extraction time, temperature, and amount of salt were evaluated. It was shown that ATPS was superior to HF-LPME for determination of paclobutrazol and uniconazole under the optimum conditions. The limits of detection (LODs) of ATPS were 0.002 μg g(-1) for uniconazole and 0.01 μg g(-1) for paclobutrazol, whereas LODs of HF-LPME were 0.005 μg g(-1) and 0.03 μg g(-1), respectively. Relative standard deviations (RSDs, n=5) and recovery were in the range 1.7-5.3 % and 86-102 %, respectively, for ATPS and 6.7-7.9 % and 40-60 % for HF-LPME. In addition, the advantages of ATPS were shorter extraction time, suitable for simultaneous pretreatment of batches of samples, and higher extraction capacity. ATPS was therefore applied to the determination of paclobutrazol and uniconazole in real soil samples. Uniconazole was detected in all the samples analyzed whereas paclobutrazol was not found.


KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation.
Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is a transmembrane glycoprotein that is expressed by natural killer (NK) cells and certain subsets of T cells. However, its expression profiles and functions in solid tumor progression remain poorly defined. In the present study, using bioinformatics analysis, immunohistochemistry, immunoblotting, MTT cell viability assay, soft agar colony formation assay and a human renal cell carcinoma (RCC) cell xenograft model in nude mice, we examined whether KIR2DL4 is expressed by RCC and its possible roles in RCC progression. We confirmed that KIR2DL4 is overexpressed by RCC cells. MTT and soft agar cloning assays showed that KIR2DL4 knockdown delayed cell proliferation and viability in RCC cell lines, Caki-1 and 769-P, in vitro. By contrast, KIR2DL4 overexpression promoted Caki-1 cell proliferation both in vitro and in vivo, which was observed in a BALB/c-nu/nu xenograft mouse model. Moreover, RNA sequencing data demonstrated that the differentially expressed genes found between parallel-controlled and Caki-1 cells overexpressing KIR2DL4 were highly associated with cancer development, of which those related to the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were particularly enriched, immunoblotting data showed that the level of AKT phosphorylation was higher or lower in KIR2DL4 overexpressing or KIR2DL4 knocking-down Caki-1 cells compared with that in the parallel-controlled cells. In addition, PI3K inhibitor wortmannin treatment and KIR2DL4-shRNA transfection further deregulated the levels of phosphorylated AKT and Caki-1 cell proliferation. Our results indicate that KIR2DL4 is also expressed by RCC cells, which promotes RCC progression associated with PI3K/AKT activation.


Hemolytic Anemia in Inflammatory Bowel Disease: Our "Gut" Tells Us to Blame the Drug.
Several studies determined that autoimmune hemolytic anemia (AIHA) is a rare extraintestinal IBD manifestation, related to the underlying disease activity. However, evidence linking biologic therapy to AIHA is sparse. This article reviews the evidence on the association of these clinical phenomena. There are two retrospective studies and a few case reports linking biologic therapies to AIHA. While some autoimmune phenomenon triggered by our biologic therapies have been well recognized, we do not find the evidence associating these therapies to AIHA sufficiently compelling.


Helicobacter pylori VacA toxin up-regulates vascular endothelial growth factor expression in MKN 28 gastric cells through an epidermal growth factor receptor-, cyclooxygenase-2-dependent mechanism.
Helicobacter pylori causes gastric damage and is involved in gastric carcinogenesis. Vascular endothelial growth factor (VEGF) plays a major role in gastric mucosa repair and is overexpressed in gastric cancer. We investigated: (a) whether H. pylori, and in particular H. pylori VacA toxin, affected VEGF expression in gastric epithelial cells in culture; and (b) the signal transduction pathway involved in any effect exerted by H. pylori. MKN-28 cells were incubated with uninoculated BCF (control) or with BCF obtained from VacA-producing wild-type H. pylori 60190 strain or from its isogenic mutant 60190:v1, specifically lacking vacA gene in the presence or absence of ZD 1839, a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, PD098059, a selective inhibitor of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase, the kinase responsible for ERK phosphorylation, or SC-236, a selective inhibitor of cyclooxygenase (COX)-2 for 24-48 h. (a) Toxigenic H. pylori up-regulated VEGF mRNA and protein expression and caused a 2.5-fold increase in VEGF release compared with control, whereas nontoxigenic H. pylori did not; (b) H. pylori VacA toxin-induced up-regulation of VEGF was counteracted by selective inhibition of EGFR tyrosine kinase; (c) toxigenic H. pylori activated the ERK/MAP kinase cascade, and inhibition of MAP kinase activation counteracted H. pylori-induced VEGF up-regulation; (d) toxigenic H. pylori up-regulated COX-2 expression, and this effect was counteracted by blockade of EGFR tyrosine kinase; and (e) COX-2 selective inhibition counteracted H. pylori-induced up-regulation of VEGF. (a) H. pylori up-regulates VEGF expression in gastric epithelial cells; and (b) this effect is specifically related to VacA toxin and seems to depend on the activation of an EGFR-, MAP kinase-, and COX-2-mediated pathway.


[Liver diseases in the elderly].
Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice.


Pseudodiabetes-not a contraindication for metabolic interventions.
Type-2 diabetes is characterized by glycosuria, hyperglycemia, glucose intolerance, hyperinsulinemia, and insulin resistance. One or several among these alterations are also found after starvation, ketogenic diet, and pharmacological treatment with rapamycin or antibody-mediated neutralization of the obesogenic factor ACBP/DBI. Thus, a variety of metabolic interventions that improve metabolic health can induce a transient state of "pseudo-diabetes".


Vortex beam propagation through atmospheric turbulence and topological charge conservation.
The propagation of vortex beams through weak-to-strong atmospheric turbulence is simulated and analyzed. It is demonstrated that the topological charge of such a beam is a robust quantity that could be used as an information carrier in optical communications. The advantages and limitations of such an approach are discussed.


Mesotherapy using Vitamin C as an anti-inflammatory agent in persistent gingival inflammation: A case series.
Mesotherapy is a minimally invasive procedure which involves local intradermal therapy (LIT) with biologically active substances given in minor quantities to the area of pathology. Vitamin C is an important antioxidant agent which can modulate the attenuation of inflammatory process and enhance tissue repair. The aim of this study was to investigate the efficacy of local injections of Vitamin C for treating persisting inflammation of the gingiva. After phase I therapy was completed, five patients with persisting chronic inflammation of the gingiva were injected with the same dosages of Vitamin C into the gingival tissues. Patients were evaluated each week for resolution of gingival inflammation. Clinical observation showed a significant improvement in inflammation of the injected sites during recall appointments. LIT with Vitamin C has a synergistic interaction along with scaling and root planing in the treatment of persistent gingival inflammation.


Similarities between explicit and implicit motor imagery in mental rotation of hands: an EEG study.
Chronometric and imaging studies have shown that motor imagery is used implicitly during mental rotation tasks in which subjects for example judge the laterality of human hand pictures at various orientations. Since explicit motor imagery is known to activate the sensorimotor areas of the cortex, mental rotation is expected to do similar if it involves a form of motor imagery. So far, functional magnetic resonance imaging and positron emission tomography have been used to study mental rotation and less attention has been paid to electroencephalogram (EEG) which offers a high time-frequency resolution. The time-frequency analysis is an established method for studying explicit motor imagery. Although hand mental rotation is claimed to involve motor imagery, the time-frequency characteristics of mental rotation have never been compared with those of explicit motor imagery. In this study, time-frequency responses of EEG recorded during explicit motor imagery and during a mental rotation task, inducing implicit motor imagery, were compared. Fifteen right-handed healthy volunteers performed motor imagery of hands in one condition and hand laterality judgement tasks in another while EEG of the whole head was recorded. The hand laterality judgement was the mental rotation task used to induce implicit motor imagery. The time-frequency analysis and sLORETA localisation of the EEG showed that the activities in the sensorimotor areas had similar spatial and time-frequency characteristics in explicit motor imagery and implicit motor imagery conditions. Furthermore this sensorimotor activity was different for the left and for the right hand in both explicit and implicit motor imagery. This result supports that motor imagery is used during mental rotation and that it can be detected and studied with EEG technology. This result should encourage the use of mental rotation of body parts in rehabilitation programmes in a similar manner as motor imagery.


Association between specialist compensation and Accountable Care Organization performance.
To determine if Medicare Shared Savings Program Accountable Care Organizations (ACOs) using cost reduction measures in specialist compensation demonstrated better performance. National, cross-sectional survey data on ACOs (2013-2015) linked to public-use data on ACO performance (2014-2016). We compared characteristics of ACOs that did and did not report use of cost reduction measures in specialist compensation and determined the association between using this approach and ACO savings, outpatient spending, and specialist visit rates. Of 160 ACOs surveyed, 26 percent reported using cost reduction measures to help determine specialist compensation. ACOs using cost reduction in specialist compensation were more often physician-led (68.3 vs 49.6 percent) and served higher-risk patients (mean Hierarchical Condition Category score 1.09 vs 1.05). These ACOs had similar savings per beneficiary year (adjusted difference $82.6 [95% CI -77.9, 243.1]), outpatient spending per beneficiary year (-24.0 [95% CI -248.9, 200.8]), and specialist visits per 1000 beneficiary years (369.7 [95% CI -9.3, 748.7]). Incentivizing specialists on cost reduction was not associated with ACO savings in the short term. Further work is needed to determine the most effective approach to engage specialists in ACO efforts.


An evaluation of the inter-observer and intra-observer variability of the ultrasound diagnosis of polycystic ovaries.
This prospective observational study was undertaken to evaluate the reliability and consistency of ultrasound diagnosis of polycystic ovarian syndrome (PCOS). Eighteen women with clinical and biochemical features suggestive of PCOS and nine normal control women underwent transvaginal ultrasound scan by a single ultrasonographer. The 27 ovarian scans were video-recorded and the recordings were later edited and arranged randomly so that each record appeared twice at random on the tape producing a total of 54 ovarian scans. Four experienced observers independently reviewed the recordings. The observers scored each case as follows: normal, possible polycystic ovary (PCO) and definite PCO. The mean intra-observer agreement was 69.4% (kappa = 0.54) and the mean inter-observer agreement was 51% (kappa = 0.28). The results suggest that the currently used ultrasonographic criteria for the diagnosis of polycystic ovaries do have significant intra-observer and inter-observer variability and as such must be considered subjective. Transvaginal ultrasonography alone may not therefore be a reliable method of diagnosing or excluding PCOS.


[Influence of climate factors on the course of secretory otitis media].
For many years there has been admitted a close link between climatology and the course of secretory otitis media. Despite of that there are few articles in medical literature covering this subject. As a consequence of the special climate of their Island the AA. study the evolutive run of the illness under different rates of humidity.


ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms.
ADAMTS-4 (aggrecanase 1) is synthesized as a latent precursor protein that may require activation through removal of its prodomain before it can exert catalytic activity. We examined various proteinases as well as auto-activation under a wide range of conditions for removal of the prodomain and induction of enzymatic activity. The proprotein convertases, furin, PACE4, and PC5/6 efficiently removed the prodomain through cleavage at Arg(212)/Phe(213), generating an active enzyme. Of a broad range of proteases evaluated, only MMP-9 and trypsin were capable of removing the prodomain. In the presence of mercuric compounds, removal of the prodomain through autocatalysis was not observed, nor was it observed at temperatures from 22 to 65 degrees C, at ionic strengths from 0.1 to 1M, or at acidic/neutral pH. At basic pH 8-10, removal of the prodomain by autocatalysis occurred, generating an active enzyme. In conclusion, the pro-form of ADAMTS-4 is not catalytically active and only a limited number of mechanisms mediate its N-terminal activation.


Cross-national attitudes about paid parental leave offerings for fathers.
Using cross-national data from the 2012 International Social Survey Programme (N = 33,273), this study considers institutional, self-interest, and ideational factors in analyzing public opinions about the provision, length, and source of paid parental leave offerings for fathers. We find substantial support for generous leave offerings. Multilevel regression results reveal that being a woman, supporting dual-earning expectations, and realizing more family strains lead to support for more generous leave offerings. Endorsing separate spheres and intensive mothering attitudes reduces support for more generous leave offerings; although, gendered attitudes interact with one another in predicting leave preferences, too. Finally, country-level indicators of female empowerment and father-specific leave offerings are positively associated with preferences for more generous leave offerings. Overall, public opinions about fathers' leave offerings across OECD countries largely support policies that provide opportunities for more involved fathering, but preferences continue to be gendered and linked to family strains and country-level contexts.


Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series.
A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.


Integrated 3D-printed reactionware for chemical synthesis and analysis.
Three-dimensional (3D) printing has the potential to transform science and technology by creating bespoke, low-cost appliances that previously required dedicated facilities to make. An attractive, but unexplored, application is to use a 3D printer to initiate chemical reactions by printing the reagents directly into a 3D reactionware matrix, and so put reactionware design, construction and operation under digital control. Here, using a low-cost 3D printer and open-source design software we produced reactionware for organic and inorganic synthesis, which included printed-in catalysts and other architectures with printed-in components for electrochemical and spectroscopic analysis. This enabled reactions to be monitored in situ so that different reactionware architectures could be screened for their efficacy for a given process, with a digital feedback mechanism for device optimization. Furthermore, solely by modifying reactionware architecture, reaction outcomes can be altered. Taken together, this approach constitutes a relatively cheap, automated and reconfigurable chemical discovery platform that makes techniques from chemical engineering accessible to typical synthetic laboratories.


Disparities in SARS-CoV-2 Vaccination-to-Infection Risk During the COVID-19 Pandemic in Massachusetts.
This cohort study examines the alignment of vaccination and SARS-CoV-2 risk in Massachusetts by creating and applying a vaccination-to-infection risk ratio.


A Protocol to Develop Practice Guidelines for Primary Care Medical Service Trips.
North American clinicians are increasingly participating in medical service trips (MSTs) that provide primary healthcare in Latin America and the Caribbean. Literature reviews have shown that the existence and use of evidence-based guidelines by these groups are limited, which presents potential for harm. This paper proposes a 5-step methodology to develop protocols for diagnosis and treatment of conditions encountered by MST clinicians. We reviewed the 2010 American College of Physicians guidance statement on guidelines development and developed our own adaptation. Ancestry search of the American College of Physicians statement identified specific publications that provided additional detail on key steps in the guideline development process, with additional focus given to evidence, equity, and local adaptation considerations. Our adaptation produced a 5-step process for developing locally optimized protocols for diagnosis and treatment of common conditions seen in MSTs. For specified conditions, this process includes: 1) a focused environmental scan of current practices based on grey literature protocols from MST sending organizations; 2) a review of relevant practice guidelines; 3) a literature review assessing the epidemiology, diagnosis, and treatment of the specified condition; 4) an eDelphi process with experts representing MST and Latin American and the Caribbean partner organizations assessing identified guidelines; and 5) external peer review and summary. This protocol will enable the creation of practice guidelines that are based on best available evidence, local knowledge, and equitable considerations. The development of guidelines using this process could optimize the conduct of MSTs, while prioritizing input from local community partners.


Project team investigates how the Association's organizational structure can be improved to meet future changes, challenges.
The members of the Project Team realize that this is a very different concept than that to which members are accustomed. The details of such a change would be developed with member input, and the new structure would be phased in over a period of several years to be fully implemented by the year 2000.


In-situ transformation to accordion-like core-shell structured metal@metallic hydroxide nanosheet from nanorod morphology for overall water-splitting in alkaline media.
Exploring highly-efficient, low-cost and earth-abundant bi-functional electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) have a key role in economical overall water-splitting. Herein, a facile and general route is developed to prepare various non-noble metal-based electrocatalysts via NH3⋅H2O treatment (NT) on Ni foam (NF) (M-NT/NF, M = Co, Ni, Fe, Mn, Cu). The morphology and compositions of the obtained catalysts could be tuned via solvothermal process with NH3⋅H2O, and then optimizing the active sites exposure and effectively change the reaction kinetics of the electrocatalytic reaction. Moreover, the substrate of Ni foam is in favor of electrolyte transfer and release of produced gases. Then, the obtain Co-NT/NF, composed of metallic Co and Co(OH)2, exhibits excellent catalytic performance for HER with low overpotential of 178 mV@10 mA cm-2 and small Tafel slope of 75 mV dec-1, which is rarely reported for HER. For OER, only a low overpotential of 226 mV is required to deliver 10 mA cm-2 with a small Tafel slope of 46 mV dec-1. Moreover, the reported electrocatalysts present negligible current density loss during long-term stability measurement, demonstrating robust nanostructure feature of the prepared catalysts. This work opens a facile and efficient avenue to design bi-funtional electrocatalyst coupling with outstanding catalytic performance.


The Effectiveness of the Super Skills for Life (SSL) Programme in Promoting Mental Wellbeing among Institutionalised Adolescents in Malaysia: An Interventional Study.
Mental health issues have become more prevalent among institutionalised adolescents. Therefore an effective intervention programme is needed to improve their mental health. To evaluate the effectiveness of the Super Skills for Life (SSL) programme in improving the mental wellbeing of institutionalised adolescents and determine the factors associated with their mental wellbeing. A quasi-experimental study involving 80 female institutionalised adolescents divided into intervention and control groups was conducted. Intervention involved implementation of the SSL programme. The effectiveness of the programme was evaluated based on several outcome parameters. Factors including age, number of family members, perceived social support and self-esteem had significant correlations with mental wellbeing of participants. The SSL programme significantly improved the anxiety and stress levels of participants. SSL programme exclusively improves the mental wellbeing in institutionalised adolescents.


Prevalence of H1299R polymorphism in the Factor V gene among the Taif-Saudi Arabia population using polymerase chain reaction-reverse hybridization technique.
Cardiovascular disease (CVD) remains a major health hazard worldwide. Single nucleotide polymorphisms (SNPs) represent a part of risk factors that contributes to cardiovascular disease. SNP in the coagulation factor V genes have been shown to play a role in the development of cardiovascular disease. Coagulation Factor V is an enzyme cofactor of the coagulation system and contributes to a normal haemostatic balance. The His1299Arg polymorphism in the Factor V gene has been identified and linked to hereditary thrombophilia. The aim of the present study is to determine the prevalence of HR2 haplotype and allele frequency of His1299Arg polymorphism in the Factor V gene among randomly selected healthy individuals from Taif population which belonging to western region of Saudi Arabia. Genotyping of this SNP was carried out via CVD StripAssay, which based on a polymerase chain reaction-reverse hybridization technique. Two hundred healthy unrelated individuals were included in the study. Seventeen out of the studied population (8.5%) had the HR2 haplotype; 14 (7%) were heterozygous (R1/R2), and three (1.5%) were homozygous (R2/R2), with an allelic frequency of 0.05. This is the first report for a Saudi Arabian population that estimates the prevalence of HR2 haplotype and its allele frequencies. In conclusion, the His1299Arg mutant was noticeable within population of western Saudi Arabia. Further larger studies are needed to (1) estimate the prevalence of this mutant among individuals belonging to different KSA locations (2) assess the relative contribution of this mutational event separately and in combination with other thrombophilic polymorphisms in the etiology of cardiovascular disease in KSA.


Manipulating fat content of familiar foods at test-meals does not affect intake and liking of these foods among children.
We investigated effects of manipulating fat content of familiar foods at two test-meals in 74, 4-6-year-old children. Liking, energy intake, and weight-based food intake were assessed for a meal consisting of macaroni and cheese, pudding, chocolate milk and regular milk in high-fat and low-fat versions. Liking ratings and consumption by weight did not differ between versions, but energy intake was 59% greater with the high-fat version. We conclude that manipulating fat content had little effect on liking and weight-based food intake, but markedly influenced overall energy intake, and thus might provide a means of lowering children's energy consumption.


Biochemical markers of type II collagen breakdown and synthesis are positioned at specific sites in human osteoarthritic knee cartilage.
To investigate whether type II collagen turnover markers used for osteoarthritis (OA) activity evaluation in body fluids can be detected at the level of specific histological features of OA cartilage tissue, as well as how they relate with each other at this level. Adjacent sections were obtained from full-depth cartilage biopsies from 32 OA knees. Immunohistochemistry was performed for Helix-II and CTX-II, which are type II collagen fragments originating from the triple helix and the telopeptide region, respectively, and believed to reflect distinct breakdown events, as well as for type IIA N propeptide (PIIANP), a biochemical marker reflecting synthesis of type IIA collagen. Helix-II and CTX-II were detected in areas where collagen damage was reported previously, most frequently around chondrocytes, but also frequently in regions not previously investigated such as the margin area and close to subchondral bone, including vascularization sites and bone-cartilage interface. The latter is CTX-II's prevailing position and shows rarely Helix-II. PIIANP co-localized with Helix-II and CTX-II on a limited number of features, mainly in deep zone cartilage. Overall, our analysis highlights clear patterns of association of the markers with specific histological features, and shows that they spread to these features in an ordered way. Helix-II and CTX-II show to some degree differential selectivity for specific features in cartilage tissue. CTX-II detection close to bone may be relevant to the possible role of subchondral bone in OA. The restricted co-localization of breakdown markers and PIIANP suggests that collagen fragments can result only partially from newly synthesized collagen. Our study strengthens the interest for the question whether combining several markers reflecting different regional cartilage contributions or metabolic processes should allow a broader detection of OA activity.


Complications of video-assisted gastrostomy in children with malignancies or neurological diseases.
To test the hypothesis whether the administration of cytostatic drugs close to surgery in children with malignancies influences the rate of postoperative complications. Included in the study were 27 children with malignancies and a control group of 27 neurologically impaired children. All the children had nutritional problems and underwent a video-assisted gastrostomy (VAG) operation during the period 1997-2002. The children were postoperatively followed up. All complications were documented according to a protocol by a specially trained nurse and correlated to the time elapsed from completion of the last preoperative or the first postoperative cytostatic drug treatment. The complications in the two groups were compared. The children with malignant diseases did not have more postoperative complications of the VAG than those having neurological defects. There was no correlation to complications regarding timing of the operation and administration of cytostatic drugs. This study revealed no aggravated influence of cytostatic drug treatment on early postoperative problems of VAG. The timing of cytostatic drug administration in relation to the surgical intervention did not influence the frequency of postoperative complications.