Comparative analysis of fecal fat quantitation via nuclear magnetic resonance spectroscopy (1H NMR) and gravimetry.
Fecal-fat is typically measured by extracting lipid from homogenized feces with subsequent gravimetric/titrimetric analyses that are time-consuming and involve toxic solvents. Accordingly, an efficient and more safe method to quantitate fecal-fat is needed. The present objective was to adapt CEM SmartTrac technology (i.e. (1)H NMR) to rapidly (< 5 min) quantitate fecal-fat and compare (1)H NMR and gravimetric performance characteristics. (1)H NMR and gravimetric measurements of stool-fat were conducted using excess stool samples (72 h collection; n=107) homogenized to semi-liquid consistency prior to analyses. The (1)H NMR method demonstrated acceptable linearity (R(2)=0.9999) and recovery (mean=105%) with imprecision (intra-assay CV=1.2-6.5%; inter-assay CV=1.8-5.8%) comparable to or better than gravimetry (intra-assay CV=1.0-17.2%; inter-assay CV=3.8-6.5%). Excellent correlation between fecal-fat quantitation by (1)H NMR and gravimetry (n=107; R(2)=0.983; y=1.0173x-0.6859) was exhibited; moreover, (1)H NMR demonstrated good sensitivity (92.3%), specificity (94.5%), negative-predictive value (92.9%) and positive-predictive value (94.1%) for malabsorption using the reference cut-off of < or = 7 g fat/24 h. These data demonstrate that (1)H NMR permits rapid and safe quantitation of fecal-fat while maintaining acceptable performance characteristics, thereby supporting the utility of (1)H NMR as an alternative method to gravimetry for fecal-fat quantitation.


[Pediatrics on the internet].
It is easy to use Internet tools with a computer's mouse but it is more difficult to obtain available addresses in order to reply to concrete and accurate search. The aim of this article is to help new Internet users in their quest for pediatric informations and medical knowledge.


Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985: evidence for increasing occurrence of the disease.
Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3.4 per 100,000. On December 31, 1985, the prevalence rate was 69 per 100,000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100,000 in the triennial periods 1965-1967, 1968-1970, and 1971-1973, and around five in each triennium from 1977 onward.


Autocrine growth factor revisited: PC-cell-derived growth factor (progranulin), a critical player in breast cancer tumorigenesis.
PC-cell derived growth factor (PCDGF), also known as granulin precursor or progranulin, is the largest member of a family of growth modulators characterized by a unique cysteine-rich motif. Biological and pathological studies point out to the importance of this growth factor in breast cancer and other human cancers, where it stimulates proliferation and survival, and promotes metastasis. These studies suggest that PCDGF is a suitable therapeutic and diagnostic target for the development of novel cancer therapy and diagnosis.


Protective effects of amoxicillin and probiotics on colon disorders in an experimental model of acute diverticulitis disease.
Acute diverticulitis disease is associated with inflammation and infection in the colon diverticula and may lead to severe morbidity. This study aimed to evaluate and compare the protective effects of amoxicillin antibiotic, either alone or in combination with probiotics (Lactobacillus acidophilus and Bifidobacterium lactis), in a rat model of acute diverticulitis disease. Acute diverticulitis was induced, in albino rats, by adding 3% weight/volume of dextran sulfate sodium (DSS) to the rats' drinking water; daily for 7 days, in addition to injecting lipopolysaccharide (LPS) enema (4 mg/kg). The impact of treatments was assessed by measuring the physiological and immunological parameters and evaluating colon macroscopic and microscopic lesions. The results showed that both treatments (especially probiotics with amoxicillin) alleviated the adverse effects of DSS and LPS. This was obvious through the modulation of the rats' body weight and the colon weight-to-length ratio. Also, there was a significant (p < 0.001) decrease in the colon macroscopic lesion score. The pro-inflammatory cytokines [(TNF)-α, (IL)-1β, (IFN)-γ, and (IL)-18]; in the colon tissue; were significantly (p < 0.001) decreased. Also, both treatments significantly ameliorated the elevation of myeloperoxidase activity and C-reactive protein levels, in addition to improving the histopathological alterations in the colon tissue. In conclusion, amoxicillin and probiotics-amoxicillin were effective in preventing the development of experimentally induced acute diverticulitis, through their anti-inflammatory and immunomodulatory effects. Furthermore, this study has explored the role of probiotics in preventing DSS/LPS-induced acute diverticulitis, so it can be applied as a promising treatment option for acute diverticulitis disease.


Don't stop me now: A qualitative study of how Brazilian dancers and staff perceive injury and its prevention.
To investigate how Brazilian dancers and dance staff perceive and deal with injury and its prevention in professional and non-professional contexts. Qualitative study. Semi-structured interviews conducted using an online platform. Thirteen participants (8 women, 5 men) from four different dance styles (classical ballet, jazz, contemporary and urban): 6 dancers, 6 staff and 1 classified as both. Interviews were recorded, transcribed and analyzed based on Grounded Theory principles using comparative data analysis. The main themes and findings were: 1) Injury definition: Injury was defined and classified based on pain, structural damage and consequent limitations and restrictions. 2) Dealing with injury: Dancers' fear of having to stop dancing justifies different behaviours facing injury. 3) Injury factors: Overload and many personal and environmental factors were perceived as related to injury. 4) Injury prevention: it is linked with physical preparation and additional measures and influenced by communication, trust, experience, time, access to preventive programs, dancers' personalities and environmental factors. Responsibility for injury prevention should be shared by all stakeholders. To improve injury prevention, we need to acknowledge the dancers' drive to keep dancing, consider the multiple factors that influence their behaviours, and develop education and self-efficacy to help them make better decisions to reduce the risk of injury.


Characteristics of earlier atherosclerotic involvement in adolescent patients with Kawasaki disease and coronary artery lesions: significance of gray scale median on B-mode ultrasound.
To test the hypothesis that textural changes in the carotid intima-media complex (IMC) detected by B-mode ultrasound are associated with the difference of remodeling process in earlier atherosclerotic involvement in patients with Kawasaki disease (KD) and coronary artery lesions (CALs). Eighteen patients with KD and CALs (mean age 17.2 years), 17 patients with heterozygous familial hypercholesterolemia (FH) (mean age 16.9 years) and 15 age-matched healthy controls (Cont) were assessed and compared for carotid intima-media thickness (CIMT), elastic property (E(p)), and first- and second-order statistics. KD showed significantly higher gray scale median (GSM) than FH and Cont. KD and FH showed significantly higher CIMT, entropy and lower angular second moment than Cont, but no significant difference was found between KD and FH. Higher GSM in KD may indicate alteration of tissue components and heterogeneity of IMC, suggesting the development of arteriosclerotic vascular remodeling after vasculitis. This is distinct from that of atherosclerosis with lower GSM often observed in FH.


Improving disturbance rejection of PI controllers by means of the magnitude optimum method.
The magnitude optimum (MO) method provides a relatively fast and nonoscillatory closed-loop tracking response for a large class of process models frequently encountered in the process and chemical industries. However, the deficiency of the method is poor disturbance rejection when controlling low-order processes. In this paper, the MO criterion is modified in order to optimize disturbance rejection performance, while the tracking performance has been improved by an integral set-point filtering PI controller structure. The new tuning rules, referred to as the disturbance rejection magnitude optimum (DRMO) method, were applied to several different two-degrees-of-freedom PI controllers. The DRMO method has also been tested on several different representatives of process models. The results of experiments have shown that the proposed tuning method with the integral set-point filtering PI controller is quite efficient in improving disturbance rejection performance, while retaining tracking performance comparable to the original MO method.


Plasma factors influencing prostacyclin-like activity in patients with diabetic microangiopathy.
Plasma factors influencing PGI2-like activity in 19 patients with diabetes mellitus /Dm/ and 17 controls were studied through a comparison with the signs of retinal and glomerular angiopathy. The plasma PGI2 supporting activity /PSA/ was lower in 15 Dm cases than in the controls. Inhibitory activity against PGI2 production was detected in 6 patients. In the cases of more serious retinopathy associated with glomerulopathy, a significantly lower level of PSA was observed than in patients with mild retinopathy without glomerular diseases. The plasma concentrations of total and LDL-cholesterol were significantly higher, while the level of HDL-cholesterol was lower than in the controls. There was a positive correlation between PSA and HDL-cholesterol values and a negative correlation between PSA and LDL-cholesterol levels, which relates to an inhibitory effect of LDL and a protective role of HDL in PGI2 synthesis.


Correlates of pulse pressure reduction during antihypertensive treatment (losartan or atenolol) in hypertensive patients with electrocardiographic left ventricular hypertrophy (the LIFE study).
In hypertensive patients, pulse pressure has been related to hypertension-induced target organ damage and risk of cardiovascular events. However, correlates of pulse pressure reduction during antihypertensive treatment have been less extensively investigated. We related pulse pressure changes to clinical and echocardiographic findings before and after 2 years of antihypertensive treatment in 767 patients aged 55 to 80 years (mean 66) in the Losartan Intervention For End point reduction in hypertension study. Over 2 years, blood pressure and pulse pressure were reduced from 173/98 to 147/84 mm Hg and from 75 to 63 mm Hg, respectively, both p <0.001. In linear multivariate analysis controlling for initial pulse pressure, 2-year reduction in pulse pressure correlated negatively with age and concomitant diabetes mellitus, and positively with body height and 2-year reduction in mean blood pressure (multiple R(2) = 0.42, p <0.01). When dividing the study population into 2 groups using a prognostically validated partition for pulse pressure, patients with pulse pressure > or =63 mm Hg after 2 years of antihypertensive treatment (n = 349) were older and shorter, included more women and patients with isolated systolic hypertension, diabetes mellitus, albuminuria, and echocardiographic left ventricular hypertrophy at baseline, and also had a smaller decrease in mean blood pressure and the urinary albumin/creatinine ratio over 2 years (all p <0.05). Thus, in hypertensive patients with electrocardiographic left ventricular hypertrophy, older age, less reduction in mean blood pressure, concomitant diabetes mellitus, and shorter stature are associated with attenuated pulse pressure reduction during antihypertensive treatment.


Bacterial agents associated with bronchopulmonary disorders in eastern Nigeria.
Altogether 16,539 sputum specimens were examined microbiologically from 1980 to 1984. Out of these 12,588 were screened by Ziehl-Neelsen's staining technique and 782 were (6.3%) found AFB-positive. Age and sex distributions of the AFB-positive individuals were statistically significant (at 0.05), incidence being most prevalent among those 20 years and above (90.2%) and among males (61.2%). From other specimens cultured, non-AFB organisms were isolated at the following frequencies: coliform-like organisms (15.1%), Streptococcus pneumoniae (55.5%). Klebsiella pneumoniae (5.3%), Streptococcus pyogenes (3.9%), Pseudomonas aeruginosa (3.4%), Haemophilus influenzae (3.0%). Proteus Spp. (0.7%) and Escherichia coli (0.5%). The antibiogram of these isolates revealed a high incidence of multiple antibiotic resistance, a situation that has most probably arisen from the high degree of antibiotic misuse in Nigeria.


Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin.
QTc interval prolongation can occur as a result of treatment with both conventional and novel antipsychotic medications and is of clinical concern because of its association with the potentially fatal ventricular arrhythmia, torsade de pointes. One case is described in which a patient with schizophrenia, who was being treated for dyslipidemia, developed a prolonged QTc interval while taking quetiapine and lovastatin. QTc returned to baseline when the lovastatin dose was reduced. QTc prolongation associated with antipsychotic medication occurs in a dose-dependent manner. We therefore hypothesize that the addition of lovastatin caused an increase in plasma quetiapine levels through competitive inhibition of the cytochrome P(450) (CYP) isoenzyme 3A4. Our case highlights the potential for a drug interaction between quetiapine and lovastatin leading to QTc prolongation during the management of dysipidemia in patients with schizophrenia.


The impact of self-efficacy, alexithymia and multiple traumas on posttraumatic stress disorder and psychiatric co-morbidity following epileptic seizures: a moderated mediation analysis.
This study investigated the incidence of posttraumatic stress disorder (PTSD) and psychiatric co-morbidity following epileptic seizure, whether alexithymia mediated the relationship between self-efficacy and psychiatric outcomes, and whether the mediational effect was moderated by the severity of PTSD from other traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited from support groups in the United Kingdom completed the Posttraumatic Stress Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and 22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD following one other traumatic life event respectively. For the control group, 24% met the diagnostic criteria for PTSD following other traumatic life events. The epilepsy group reported significantly more anxiety and depression than the control. Partial least squares (PLS) analysis showed that self-efficacy was significantly correlated with alexithymia, post-epileptic seizure PTSD and psychiatric co-morbidity. Alexithymia was also significantly correlated with post-epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed that alexithymia mediated the path between self-efficacy and post-epileptic seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed that self-efficacy and PTSD from one other trauma moderated the effect of alexithymia on outcomes. To conclude, people can develop posttraumatic stress disorder symptoms and psychiatric co-morbidity following epileptic seizure. These psychiatric outcomes are closely linked with their belief in personal competence to deal with stressful situations and regulate their own functioning, to process rather than defend against distressing emotions, and with the degree of PTSD from other traumas.


High-flow oxygen therapy in immunocompromised patients with acute respiratory failure: A review and meta-analysis.
Acute respiratory failure remains a common hazardous complication in immunocompromised patients and is associated with increased mortality rates when endotracheal intubation is need. We aimed to evaluate the effect of high-flow nasal cannula oxygen therapy (HFNC) compared with other oxygen technique for this patient population. We searched Cochrane library, Embase, PubMed databases before Aug. 15, 2017 for eligible articles. A meta-analysis was performed for measuring short-term mortality (defined as ICU, hospital or 28-days mortality) and intubation rate as the primary outcomes, and length of stay in ICU as the secondary outcome. We included seven studies involving 667 patients. Use of HFNC was significantly association with a reduction in short-term mortality (RR 0.66; 95% CI, 0.52 to 0.84, p=0.0007) and intubation rate (RR 0.76, 95% CI 0.64 to 0.90; p=0.002). In addition, HFNC did not significant increase length of stay in ICU (MD 0.15days; 95% CI, -2.08 to 2.39; p=0.89). The results of current meta-analysis suggest that use of HFNC significantly improve outcomes of acute respiratory failure in immunocompromised patients. Owing to the quality of the included studies, further adequately powered randomized controlled trials are needed to confirm our results.


Metalated hybrid polymers as catalytic reagents for phosphate ester hydrolysis and plasmid modification.
Pendant pyrazolylcyclophosphazene containing hybrid cross-linked polymer (CPPL) has been utilized for binding Zn(II). The metalated polymer (CPPL-Zn) has been found to be very effective catalyst for the hydrolysis of a RNA model phosphodiester substrate [2-(hydroxypropyl)-p-nitrophenyl phosphate, hNPP]. In addition, CPPL-Zn also cleaved supercoiled plasmid DNA pBR322 thus providing a novel structural motif of inorganic-organic hybrid polymers as synthetic nucleases.


Comparison of Turkish and US haemodialysis patient mortality rates: an observational cohort study.
There are significant differences between countries in the mortality rates of haemodialysis (HD) patients. The extent of these differences and possible contributing factors are worthy of investigation. As of March 2009, all patients undergoing HD or haemodiafiltration for >3 months (n = 4041) in the Turkish clinics of the NephroCare network were enrolled. Data were prospectively collected for 2 years through the European Clinical Dialysis Database. Mean age ± standard deviation was 58.7 ± 14.7 years, 45.9% were female and 22.9% were diabetic. Comparison with US data was performed by applying an indirect standardization technique, using specific mortality rates for patients on HD by age, gender, race and primary diagnosis as provided by the 2012 US Renal Data System Annual Data Report as reference. The crude mortality rate in Turkey was 95.1 per 1000 patient-years. Compared with the US reference population, the annual mortality rate for Turkey was significantly lower, irrespective of gender, age and diabetes. After adjustments for age, gender and diabetes, the mortality risk in the Turkish cohort was 50% lower than US whites [95% confidence interval (CI) 0.46-0.54, P < 0.001], 44% lower than US African-Americans (95% CI 0.52-0.61, P < 0.001) and 20% lower than Asian-Americans (95% CI 0.74-0.86, P < 0.05). The annual mortality rate of prevalent HD patients was found to be significantly lower in the studied Turkish cohort compared with that published by the US Renal Data System Annual Data Report. Differences in practice patterns may contribute to the divergence.


Isolation and Characterization of Extracellular Vesicles from Lymphocytes.
Extracellular vesicles (EVs) are nanosized particles secreted by all cells as a means of communication. When it comes to the immune system, most of the studies have focused on the regulation of T cells by EVs derived from other cells, such as dendritic cells, tumor cells, and mesenchymal stem cells. Nevertheless, the communication between T cells, and from T cells to other cells via EVs must also exist and influence various physiological and pathological functions. Here, we describe sequential filtration; a new method for the physical isolation of vesicles based on their size. Furthermore, we describe several methods that can be applied to characterize both size and markers of the isolated EVs derived from T cells. This protocol overcomes the limitations of some of the current methods and offers a high yield of EVs from a low number of T cells.


Neuropeptide Y-mediated inhibition of proopiomelanocortin neurons in the arcuate nucleus shows enhanced desensitization in ob/ob mice.
NPY and alphaMSH are expressed in distinct neurons in the arcuate nucleus of the hypothalamus, where alphaMSH decreases and NPY increases food intake and body weight. Here we use patch-clamp electrophysiology from GFP-labeled POMC and NPY neurons to demonstrate that NPY strongly hyperpolarized POMC neurons through the Y1R-mediated activation of GIRK channels, while the alphaMSH analog, MTII, had no effect on activity of NPY neurons. While initially NPY had similar effects on POMC neurons derived from ob/ob mice, further studies revealed a significant increase in desensitization of the NPY-induced currents in POMC neurons from ob/ob mice. This increase in desensitization was specific to NPY, as GABA(B) and microOR agonists showed unaltered desensitization in POMC neurons from ob/ob mice. These data reveal an intricate and asymmetric interplay between NPY and POMC neurons in the hypothalamus and have important implications for the delineation of the neural circuits that regulate feeding behavior.


Proteome analysis of chicken embryonic gonads: identification of major proteins from cultured gonadal primordial germ cells.
The domestic chicken (Gallus gallus) is an important model for research in developmental biology because its embryonic development occurs in ovo. To examine the mechanism of embryonic germ cell development, we constructed proteome map of gonadal primordial germ cells (gPGCs) from chicken embryonic gonads. Embryonic gonads were collected from 500 embryos at 6 days of incubation, and the gPGCs were cultured in vitro until colony formed. After 7-10 days in culture, gPGC colonies were separated from gonadal stroma cells (GSCs). Soluble extracts of cultured gPGCs were then fractionated by two-dimensional gel electrophoresis (pH 4-7). A number of protein spots, including those that displayed significant expression levels, were then identified by use of matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and LC-MS/MS. Of the 89 gPGC spots examined, 50 yielded mass spectra that matched avian proteins found in on-line databases. Proteome map of this type will serve as an important reference for germ cell biology and transgenic research.


Vascular morphology and permeability in fetal CNS grafts to the renal capsule.
According to conventional neovascularization concepts, due to local tissue factors, a viable graft of central nervous (CNS) tissue should be expected to retain a complete blood-brain barrier (BBB) in its new site. In order to determine if grafted CNS would alter the phenotype of ingrowing peripheral vessels we have used an uncomplicated model. Rat fetal cortex, which already has a BBB to protein, was grafted to the subcapsular space of the host rat kidney. After postoperative times between 4 weeks and 3 months, horseradish peroxidase was injected systemically for periods between 90 s and 4 min. Correlative electron microscopy depicted vascular morphology. Each graft contained protein exudation particularly around large vessels in the neuropil. At the EM level some of the vascular endothelia had fenestrations, were invested with collagen, and were not contacted by astroglia. Capillaries indigenous to the CNS grafts and related normally to astroglial end feet were also prominent. The presence of non-CNS vessels with peripheral ultrastructural and permeability characteristics would appear to contradict conventional theory in that CNS grafts can be vascularized by vessels of a different phenotypic and physiologic nature.


A Data-Driven Iterative Approach for Semi-automatically Assessing the Correctness of Medication Value Sets: A Proof of Concept Based on Opioids.
Value sets are lists of terms (e.g., opioid medication names) and their corresponding codes from standard clinical vocabularies (e.g., RxNorm) created with the intent of supporting health information exchange and research. Value sets are manually-created and often exhibit errors. The aim of the study is to develop a semi-automatic, data-centric natural language processing (NLP) method to assess medication-related value set correctness and evaluate it on a set of opioid medication value sets. We developed an NLP algorithm that utilizes value sets containing mostly true positives and true negatives to learn lexical patterns associated with the true positives, and then employs these patterns to identify potential errors in unseen value sets. We evaluated the algorithm on a set of opioid medication value sets, using the recall, precision and F1-score metrics. We applied the trained model to assess the correctness of unseen opioid value sets based on recall. To replicate the application of the algorithm in real-world settings, a domain expert manually conducted error analysis to identify potential system and value set errors. Thirty-eight value sets were retrieved from the Value Set Authority Center, and six (two opioid, four non-opioid) were used to develop and evaluate the system. Average precision, recall, and F1-score were 0.932, 0.904, and 0.909, respectively on uncorrected value sets; and 0.958, 0.953, and 0.953, respectively after manual correction of the same value sets. On 20 unseen opioid value sets, the algorithm obtained average recall of 0.89. Error analyses revealed that the main sources of system misclassifications were differences in how opioids were coded in the value sets-while the training value sets had generic names mostly, some of the unseen value sets had new trade names and ingredients. The proposed approach is data-centric, reusable, customizable, and not resource intensive. It may help domain experts to easily validate value sets.


Parental substance abuse and function of the motivation and behavioral inhibition systems in drug-naïve youth.
It is hypothesized that the development of substance abuse (SA) may be due to imbalance in functions of the motivation-reward and behavioral inhibition systems in the brain. This speaks to the search for biological risk factors for SA in drug-naïve children who also exhibit motivational and inhibitory control deficits; however, this type of research is currently lacking. The objective of this study was to establish a neurobiological basis for addiction vulnerability using functional magnetic resonance imaging (fMRI) in drug-naïve youth with attention deficit/hyperactivity disorder (ADHD). We hypothesized that children with ADHD alone would show higher activity in regions of the motivation-reward and behavioral inhibition systems than children with ADHD and a parental history of SA. Toward this goal we scanned 20 drug-naïve children with ADHD ages 8-13 while performing an event-related reward task. High (N=10) and low (N=10) risk subjects were identified, based on parental history of SA. The effects of anticipation, conflict, and reward were assessed with appropriate linear contrasts, and between-group differences were assessed using statistical parametric mapping. The two groups did not differ on behavioral measures of the task. The fMRI results show heightened activation in the brain motivational-reward system and reduced activation of the inhibitory control system in high-risk compared to low-risk children. These results suggest that a functional mismatch between these two systems may represent one possible biological underpinning of SA risk, which is conferred by a parental history of addiction.


Ab initio and comparative 3D modeling of FAM222A-encoded protein and target-driven-based virtual screening for the identification of novel therapeutics against Alzheimer's disease.
The complex nature of Alzheimer's disease (AD) makes it difficult to understand the exact molecular processes leading to neuron death. However, two molecular factors - the production of amyloid-beta plaques and tau tangles - are considered to be linked to AD. A genetic marker for brain atrophy, FAM222A, has been identified by the unique cross-phenotype meta-analysis of genetics imaging and the molecular features show an interaction between the protein aggregatin encoded by FAM222A and amyloid beta (Aβ)-peptide (1-42) via its N-terminal Aβ binding domain, thus increasing Aβ aggregation. Function of Aggregatin protein is unclear, and its 3D structure has not been investigated in experimental analysis, so far. Hence, in the present study, first time in literature, 3D models of FAM222A-encoded Aggregatin were systematically constructed by applying diverse homology modeling approaches and they were used as target structures at the virtual screening of FDA-approved drugs and drugs currently under research in clinical trials. Then, the identified hit molecules were chosen for further molecular dynamics (MD) simulations and post-MD analyses. Our integrated ligand-based and protein-driven-based virtual screening results show that Cefpiramide, Diniprofylline, Fostriecin, and Droperidol may target Aggregatin.


[Use of self-reported values of body weight and body height in nutritional status evaluation in adolescents].
The aim of our study was to assess validity of self-reported body weight and height compared to measured values in a group of adolescents. We also investigated differences in reported and measured values and factors responsible for them in this particular population. 295 adolescents aged 11-14 (114 boys and 131 girls) attending primary schools in central Belgrade, recorded their BMI and completed a series of questionnaires measuring body satisfaction and eating patterns. All participants were measured afterwards. Differences between reported and measured weights were highly significant in girls (48.84 +/- 8.42 kg vs 49.69 +/- 9.28 kg). Significant differences between reported and measured weights were established in the group of adolescents with weight problems (-3.18 +/- 4.03 kg). Adolescents on diets presented a difference of -1.36 +/- 3.36 kg. Weight problems (OR 3.72, 95%CI: 2.10-4.75) and female gender (errors occurred more often for 22%, 95%CI: 0.23-1.80) were significant predictors in multivariate regression model for discrepancy of reported and measured weights. In a multivariate regression model, where differences in BMI were dependent variable, weight category was a significant predictor, with differences being 1.65 times more common (95%CI: 1.13-2.11). Our results suggest that self-reported body weight and height have limited reliability and can be used only in normal weight male adolescents. This method should not be recommended in surveys that involve overweight and/or obese adolescents and those who are on diet.


Structure-Activity Relationship Studies of β-Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site.
We have synthesized a series of new β-lactam-azide derivatives as orally active anti-tumor agents by targeting tubulin colchicine binding site and examined their structure activity relationship (SAR). Among them, compound 28 exhibited the most potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.106 μM by induction of G2/M arrest and apoptosis and inhibition of the epithelial to mesenchymal transition. 28 acted as a novel inhibitor of tubulin polymerization by its binding to the colchicine site. SAR analysis revealed that a hydrogen atom at the C-3 position of the β-lactam was required for the potent antiproliferative activity of β-lactam-azide derivatives. Oral administration of compound 28 also effectively inhibited MGC-803 xenograft tumor growth in vivo in nude mice without causing significant loss of body weight. These results suggested that compound 28 is a promising orally active anticancer agent with potential for development of further clinical applications.


Isolation of a lytic, pore-forming protein (perforin) from cytolytic T-lymphocytes.
Cytolytic granules from a T-cell line with specific cytolytic activity were isolated. Granules were solubilized and fractionated on a TSK 4000 gel filtration column. Lytic activity was eluted as a single retarded peak. Polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulfate indicated that the lytic fractions contained a single protein (perforin) with an apparent molecular weight of approximately 66 kDa. It separated well from the other proteins present in the granules. Isolated perforin polymerized and inserted into lipid bilayers in the presence of Ca2+, forming tubular structures with inner diameters varying from 6 to 16 nm. Lipid insertion of perforin was demonstrated using a membrane-restricted, photoactivatable probe. The lytic properties of perforin suggest an important role of this particular protein during cytolytic T-cell-mediated target cell lysis.


Diclofenac-tramadol vs. diclofenac-acetaminophen combinations for pain relief after caesarean section.
We compared the analgesic efficacy of diclofenac-acetaminophen combination with diclofenac-tramadol combination to optimize multimodal post-operative analgesia in women undergoing caesarean section. In this randomized, double-blind, parallel-group controlled trial, 204 women undergoing caesarean section under spinal anaesthesia with bupivacaine received rectal suppository diclofenac 100 mg (8 hourly till 24 h) plus either intravenous acetaminophen (1 g 6 hourly) or tramadol (75 mg 6 hourly) post-operatively. The primary outcome measure was the summed pain intensities during the entire observation period, calculated as the sum of time-weighted pain intensity scores as an area under the curve (AUC). Secondary outcome was the use of rescue analgesic, administered if the patient's numeric rating scale (NRS) scores ≥ 4. The overall pain score for the entire observation period measured as AUC was significantly lower in the diclofenac-tramadol group. However, diclofenac-tramadol combination produced Bonferroni-corrected statistically significant lower NRS pain scores only on movement at 24 h. Rescue analgesic consumption was comparable between the groups (13% vs. 12%, P = 0.872). Overall, the pain scores were low in both of the groups across various time intervals (median NRS scores 0-2 for pain both at rest and on movement), indicating satisfactory pain control in both groups. Side effects were few and comparable, except nausea (significantly more in tramadol group than acetaminophen group, 15% vs. 2%, P = 0.001). Both diclofenac-tramadol and diclofenac-acetaminophen combinations can achieve satisfactory post-operative pain control in women undergoing caesarean section. The diclofenac-tramadol combination was overall more efficacious but associated with higher incidence of post-operative nausea.


Characterization of muscle alteration in oral submucous fibrosis-seeking new evidence.
The aim of the study was to assess the progression of Oral Submucous Fibrosis (OSF) by investigating the correlation between clinical mouth opening and muscle-epithelial distance in tissue sections. Characterization of changes involving muscle was ascertained. 50 cases and 10 controls were included in this case-control study. Inter-incisal mouth opening was measured and classified according to Lai et al as Group A (more than 35 mm), Group B (30 to 35 mm), Group C (20 to 30 mm), Group D (less than 20mm). Histopathological sections were graded as very early, early, moderately advanced, advanced OSF. Muscle-epithelial distance was calculated using image analysis software. The four most common degenerative changes observed in muscles, namely fragmentation, highly eosinophilic areas with loss of striations, nucleus internalization and multiple pyknotic nuclei were also assessed. Comparisons of muscle-epithelial distance were made between the clinical and histopathological groups to those of controls. The mean muscle-epithelial distance was: Group A-626.8±309.36 µm, B-827.5±549.72 µm, C-673.2±321.93 µm, D-439.9±173.84 µm, Controls-1222.19 ±441.7 µm. Post-hoc Bonferroni Test revealed a statistically significant reduction in the muscle-epithelial distance in Group C (p-value = 0.001) and D (p-value = 0.001) as compared to controls. The mean muscle-epithelial distance in very early, early, moderately advanced and advanced OSF was 732.73±232.81 µm, 726.54±361.63 µm, 548.36±273.13 and 172.40±58.41 µm respectively. Highly significant difference in muscle-epithelial distance was seen between controls as compared to early (p-value =0.002), moderately advanced (p-value = 0.001) and advanced OSF (p-value = 0.001. Fragmentation and highly eosinophilic areas were invariably noticed in advanced OSF. Multiple pyknotic nuclei were variable with no specificity. Reduction in muscle-epithelial distance may prove to be a significant predictor of OSF progression. Degenerative changes must be noted while observing OSF cases, irrespective of the histopathological grade.


Identification of a protein increasing in serum of Nagase analbuminemic rats bearing intestinal tumors as an isotype of T-kininogen.
Increase in an unidentified protein was observed in serum of Nagase analbuminemic rats (NAR) bearing intestinal tumors induced by azoxymethane. This protein seemed to be a polymer of a protein of 73 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and so was tentatively named 73K-protein. The serum concentration of 73K-protein in NAR bearing intestinal tumors was 11.9 +/- 2.2 mg/ml (mean +/- SD, n = 5), whereas that in control NAR was 2.0 +/- 0.2 mg/ml. Increase of the serum 73K-protein level was also observed in Sprague-Dawley rats bearing intestinal tumors, skin tumors, subcutaneous sarcomas, or mammary tumors and in ACI rats bearing urinary bladder tumors. On double immunodiffusion analysis, the 73K-protein was not detected in mouse, guinea pig, pig, horse, or human serum. A cDNA clone bearing the sequence encoding 73K-protein was isolated from a cDNA library constructed from rat liver mRNA. The nucleotide sequence of the 73K-protein showed 98.8% and 96.9% homologies with the sequences of the 3'-proximal domains of the cDNAs for TI- and TII-kininogen, respectively. Therefore, the 73K-protein was concluded to be an isotype of T-kininogen.


The disulphide bonds in the catalytic domain of BACE are critical but not essential for amyloid precursor protein processing activity.
beta-Site APP-cleaving enzyme (BACE) initiates the processing of the amyloid precursor protein (APP) leading to the generation of beta-amyloid, the main component of Alzheimer's disease senile plaques. BACE (Asp2, memapsin 2) is a type I transmembrane aspartic protease responsible for the beta-secretase cleavage of APP producing a soluble form of the ectodomain (sAPPbeta) and the membrane-bound, carboxy-terminal intermediates C99 and C89. BACE maturation involves cysteine bridge formation, N -glycosylation and propeptide removal. We investigated variants of BACE in which the disulphide bonds of the catalytic domain spanning between Cys216/Cys420, Cys278/Cys443 and Cys330/Cys380 were removed by mutagenesis. When transfected in cultured cells, these mutants showed impaired maturation. Nevertheless, a fraction of mutated protein retained both the competence to mature as well as the activity to process APP. For the generation of a functional enzyme the conserved Cys330/Cys380 bond was the most critical, whereas the two bonds between Cys216/Cys420 and Cys278/Cys443, which are typical for the membrane-bound BACE, appeared to be less important.


Graft failure and revision rate after ACL repair with dynamic intraligamentary stabilization. One-year results of a prospective case series of 155 patients.
The aim of this study was to assess graft failure, revision rate, and functional outcomes after treatment of acute ACL rupture with dynamic intraligamentary stabilization (DIS) Ligamys device one year post surgery. Additionally, differences in functional outcome between patients with and without anteroposterior laxity were assessed. It was hypothesized that the failure rate of DIS was non-inferior to that of previously reported ACL reconstruction (10%). In this prospectively designed multicenter study, including patients with an acute ACL rupture, DIS was performed within 21 days after rupture. Primary outcome was failure of the graft at 1 year post surgery, defined as 1) re-rupture of the graft, 2) revision of DIS, or 3) a > 3 mm side-to-side difference in anterior tibial translation compared to the non-operated knee (∆ATT), measured by the KT1000 device. Additional analysis was performed using a 5 mm threshold. The subjective International Knee Documentation Committee Score (IKDC) and Numerical Rating Scales (NRS) for pain and confidence were used to evaluate functional outcome. A total of 155 patients were included with a mean age at surgery of 27.8 years (SD 9.4). The mean interval from rupture to DIS was 16.4 days (SD 5.2). At a median follow-up of 13 months (IQR 12-18) the failure rate of the graft was 30.2% (95%CI:22.0-39.4); 11 patients (7%) required secondary reconstructive surgery and of the 105 patients who attended ATT measurement, 24 patients (23%) had an ∆ATT > 3 mm. Secondary analysis, based on a 5 mm threshold, revealed a failure rate of 22.4% (95%CI: 15.2; 31.1). A total of 39 patients (25%) reported at least one complication, comprising mainly arthrofibrosis, traumatic re-rupture and pain. In these patients, removal of the monoblock was performed in 21 cases (13.5%). At follow-up no significant differences in functional outcomes between patients with ∆ATT > 3 mm and stable ATT were observed. This prospective multicenter study found a high failure rate at one year follow-up of 30% (7% revision surgery and 23% > 3 mm side-to-side difference in anterior tibial translation) in patients treated by primary repair of the ACL with DIS, and did therefore not demonstrate non-inferiority to ACL reconstruction. For patients who did not require secondary reconstructive surgery, this study found good functional outcomes, also in case of persistent anteroposterior knee laxity (∆ATT > 3 mm). Level IV.


[Unsaturated fatty acid of Actinidia chinesis planch seed oil protects against pulmonary fibrosis by inhibiting collagen synthesis via down-regulating connective tissue growth factor (CTGF) expression in rats].
Objective To observe the role of connective tissue growth factor (CTGF) and collagen synthesis in anti-pulmonary fibrosis (PF) by Kiwi fruit essence(unsaturated fatty acid of actinidia chinesis planch seed oil)in rats. Methods Sixty male SD rats were randomly divided into control group, model group, Kiwi fruit essence (60, 120, 240 mg/kg) treatment groups, and 5 mg/kg prednisone acetate group, with 10 animals in each group. Rats in control group were intratracheally administered with 9 g/L sodium chloride solution, and animals in other groups were intratracheally administered with bleomycin A5 to establish PF model. From the second day on, rats in the latter 4 groups were intragastrically treated with Kiwi fruit essence of 60, 120 and 240 mg/kg and prednisone acetate of 5 mg/kg, respectively. Rats in control and model groups were treated with 9 g/L sodium chloride solution once a day. All rats were sacrificed on day 28, and then pulmonary tissues were removed. The extent of PF lesions were evaluated using HE and Masson staining. The contents of hydroxyproline (HYP) were measured by a commercial kit. The mRNA expressions of CTGF and α-smooth muscle actin (α-SMA) in pulmonary tissues was detected by quantitative real-time PCR. The protein expressions of CTGF, α-SMA, collagen type 1 (Col1) and Col3 were measured by Western blotting. The protein levels of CTGF were analyzed using immunohistochemical staining. Results Compared with the model group, the alveolitis and PF extent in 60, 120, 240 mg/kg Kiwi fruit essence treatment groups as well as 5 mg/kg prednisone acetate group were significantly alleviated, and the content of HYP and the expression of CTGF, α-SMA, Col1 and Col3 decreased. The changes of above indicators were dose-dependent among the (60, 120, 240) mg/kg Kiwi fruit essence treatment groups. Moreover, the above indicators were found higher in (60, 120) mg/kg Kiwi fruit essence treatment groups than those in 5 mg/kg prednisone acetate group, which, however, showed no significantly difference between 240 mg/kg Kiwi fruit essence treatment group and 5 mg/kg prednisone acetate group. Conclusion Kiwi fruit essence down-regulates CTGF expression and decreases the levels of α-SMA, leading to inhibition of Col1 and Col3 synthesis and alleviation of PF.


[The use of muscle autograft denatured by microwave for repair of gap in removal of facial neuroma].
To study the clinical value of muscle autograft denatured by microwave for repair of gap in removal of facial neuroma. A case of patient with a larger facial nerve Schwann cell neuroma was reported. Based on the good results of our experimental research on rats recently, we completed the operation by transmastoid approach for removal of facial neuroma, and the gap of the nerve was repaired with muscle autograft denatured by microwave. The patient was followed up for one year, and her facial function recovery on the affected side was satisfactory. Muscle autograft denatured by microwave technique is convenient, highly efficient for repairing facial nerve gap after removal of facial neuroma.


Assigning cause of maternal death: a comparison of findings by a facility-based review team, an expert panel using the new ICD-MM cause classification and a computer-based program (InterVA-4).
To compare methodology used to assign cause of and factors contributing to maternal death. Reproductive Age Mortality Study. Malawi. Maternal deaths among women of reproductive age. We compared cause of death as assigned by a facility-based maternal death review team, an expert panel using the International Classification of Disease, 10th revision (ICD-10) cause classification for deaths during pregnancy, childbirth and the puerperium (ICD-MM) and a computer-based probabilistic program (InterVA-4). Number and cause of maternal deaths. The majority of maternal deaths occurred at a health facility (94/151; 62.3%). The estimated maternal mortality ratio was 363 per 100 000 live births (95% CI 307-425). There was poor agreement between cause of death assigned by a facility-based maternal death review team and an expert panel (κ = 0.37, 86 maternal deaths). The review team considered 36% of maternal deaths to be indirect and caused by non-obstetric complications (ICD-MM Group 7) whereas the expert panel considered only 17.4% to be indirect maternal deaths with 33.7% due to obstetric haemorrhage (ICD-MM Group 3). The review team incorrectly assigned a contributing condition rather than cause of death in up to 15.1% of cases. Agreement between the expert panel and InterVA-4 regarding cause of death was good (κ = 0.66, 151 maternal deaths). However, contributing conditions are not identified by InterVA-4. Training in the use of ICD-MM is needed for healthcare providers conducting maternal death reviews to be able to correctly assign underlying cause of death and contributing factors. Such information can help to identify what improvements in quality of care are needed. For maternal deaths assigning cause of death is best done by an expert panel and helps to identify where quality of care needs to be improved.


Label-free quantitative proteomic analysis of adult Drosophila heads.
LIR motif-containing proteins (LIRCPs) bind to LDS (LIR motif docking site) of Atg8-family proteins. In this protocol, we describe steps to identify Drosophila LIRCPs, in Atg8a LDS mutants we have created, via label-free quantitative proteomic analysis. We detail steps for extraction of proteins from adult Drosophila heads, followed by liquid chromatography-mass spectrometry (LC-MS/MS) analysis. We also describe screening steps of upregulated proteins in Atg8a LDS mutants, leading to identification of novel LIRCPs in Drosophila. For complete details on the use and execution of this protocol, please refer to Rahman et al. (2022).


Utilization of healthcare by immigrants in Canada: a cross-sectional analysis of the Canadian Community Health Survey.
Immigrants to Canada face unique barriers to health care, which leads to inequities in health care utilization. Lower utilization of health care by immigrants to Canada is associated with the deteriorating health of individual immigrants as well as increased costs to the health care system. The existing literature suggests that time since immigration is an important predictor for utilization of health care for Canadian immigrants; however, few studies have included this variable in their analysis. This study aims to examine the relationships between having a regular health care provider and time since immigration, and number of medical consultations in the past year and time since immigration. A secondary cross-sectional data analysis using Andersen and Newman's Framework of Health Service Utilization and data from the 2015-2016 Canadian Community Health Survey (CCHS) was conducted to examine health care utilization among immigrants in Canada. We used multiple logistic regression to examine the relationship between time since immigration and having a regular physician and negative binomial regression to compare the number of consultations of recent (less than 10 years since immigration) and established (10 or more years since immigration) immigrants. Eighty four percent of immigrant respondents to CCHS 2015-2016 had a regular health care provider. After controlling for other independent variables, established immigrants were 1.75 (95% confidence interval: 1.45-2.10) times more likely to have a regular health care provider compared to recent immigrants. Immigrants had a mean of 3.37 (standard deviation 4.53) medical consultations in the preceding year. There was no difference in the mean number of medical consultations by recent and established immigrants. After controlling for other independent variables, this study found that time since immigration had a significant effect on having a regular provider but not on number of consultations. Differences in health care utilization for recent and for established immigrants observed in this study may be partially explained by Canada's evolving immigration policy and the economic and social integration of immigrants over time.


Monopolistic structures and industrial analysis in Spain: the case of the pharmaceutical industry.
This article seeks to illustrate the monopolistic structure of the Spanish pharmaceutical industry, focusing on its many dimensions. The basic conditions of technology and demand, product differentiation, effect of advertising, and barriers to entry are considered, as is financial and economic concentration. Although economic conditions are emphasized, the ways they affect public and private health, the quality of health services, and health education are also highlighted.


Increasing feasibility and patient comfort of MRI in children with juvenile idiopathic arthritis.
MRI is the most sensitive imaging modality in juvenile idiopathic arthritis (JIA), but has practical limitations. Optimizing the scanning protocol is, therefore, necessary to increase feasibility and patient comfort. To determine the feasibility of bilateral non-contrast-enhanced open-bore MRI of knees and to assess the presence of literature-based MRI features in unsedated children with JIA. Children were classified into two clinical subgroups: active arthritis (group 1; n = 29) and inactive disease (group 2; n = 18). MRI features were evaluated using a literature-based score, comprising synovial hypertrophy, cartilage lesions, bone erosions, bone marrow changes, infrapatellar fat pad heterogeneity, effusion, tendinopathy and popliteal lymphadenopathy. The MRI examination was successfully completed in all 47 children. No scan was excluded due to poor image quality. Synovial hypertrophy was more frequent in group 1 (36.2%), but was also seen in 19.4% of the knees in group 2. Infrapatellar fat pad heterogeneity was more prevalent in group 2 (86.1%; P = 0.008). Reproducibility of the score was good (Cohen kappa, 0.49-0.96). Bilateral non-contrast-enhanced open-bore knee MRI is feasible in the assessment of disease activity in unsedated children with JIA. Signs differing among children with active and inactive disease include infrapatellar fat pad heterogeneity and synovial hypertrophy.


Determination of carcinoembryonic antigen as a tumor marker using a novel graphene-based label-free electrochemical immunosensor.
In this work, a simple label-free electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA) was developed. At first, the GC electrode was coated with partially reduced graphene oxide (rGO) to form a platform to bind the antibody. After activating the carboxyl groups of rGO through the EDC/NHS linker, the electrode surface was covered with the antibody. Then, the electrochemical behavior of the antibody-modified electrode and the parameters of the interactions of antibody-antigen immune complexes were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). This immune-complex layer was found to attenuate the electrochemical current which can be used as a good signal to determine the antigen concentration. The proposed immunosensor exhibited a good amperometric response to CEA within a concentration range of 0.1-5 ng mL-1 with a detection limit of 0.05 ng ml-1. Furthermore, the developed method was evaluated for the detection of CEA in the real sample (human blood serum), and the results were comparable with the reference values obtained by the standard enzyme-linked immunosorbent assay (ELISA). Our findings suggest the present immunosensor as a good candidate for application in clinical screening.


An engineered (CAGA)12-EGFP cell-based biosensor for high-content and accurate detection of active TGF-β.
Transforming growth factor-β (TGF-β) regulates multiple fundamental physiological processes and is closely related to severe diseases such as cancer, fibrosis, immune disorders and cardiovascular diseases. TGF-β is thus an important biomarker for clinical diagnosis and prognosis, and a crucial target for therapeutics development. Here we describe a high-content, serum-free, easy-to-use, and cost-effective (CAGA)12-EGFP cell-based biosensor for accurate measurements of active TGF-β. Together with non-destructive and continuous measurement protocol and data processing method established here, the biosensor is capable of detecting active TGF-β1 in the range of 0.024-6.25 ng/mL concentration with >91% accuracy and high repeatability. Overall, the engineered (CAGA)12-EGFP biosensor is a powerful tool for detection of active TGF-β and for mechanistic study of the TGF-β pathway. The greatly reduced cost and operating simplicity also makes it a highly potent in vitro platform for high-throughput screening of anti-TGF-β therapeutics.


Hemodynamics, prolactin and catecholamine levels during hemorrhagic shock in dogs pretreated with a prolactin inhibitor (bromocriptine).
Bromocriptin, a dopaminomimetic drug, causing inhibition of prolactin secretion, was used in experiments on haemorrhagic shock in dogs. 5 dogs were treated with bromocriptine (0.4 mg.day-1) for two days; a further 5 dogs were used as control animals. 30% of the blood volume was drawn from each dog. Mean arterial blood pressure, heart rate, central venous pressure, acid-base status, prolactin, GH and catecholamine levels were checked before blood letting and monitored until 1 hour after blood letting. Animals treated with bromocriptine showed a significant decrease of the mean arterial blood pressure and of the prolactin rate and a significant increase of catecholamine levels. Control animals, instead, showed a significant increase of the prolactine and catecholamine rates. The results obtained suggest that bromocriptine can constitute an additional hypotensive factor in subjects with acute haemorrhage. A considerable amount of research work previously carried out has shown a close correlation between stress and hyper-prolactinemia. The increase of prolactinemia and the effects of bromocriptine on this hormone during surgical stress is particularly interesting due to its possible implications (Lanza V. et coll., 1983). In previous experiments involving animals it was found that Prolactin exerts positive chronotropic and hypertensive effects (Horrobin D.F., 1977) whilst bromocriptine is a potent agonist of D2 dopaminergic receptors (Thorner M.O. et coll., 1980). Dopamine was found to be particularly useful in the clinical treatment of shock thus suggesting an involvement of peripheral D2 receptors. On the basis of these observations we have considered it worthwhile to investigate the haemodynamic effects of bromocriptine in haemorrhagic shock.


Ascariasis of the gastrointestinal tract.
The radiographic findings and complications of Ascaris lumbricoides infection of the gastrointestinal tract are presented. Since the clinical symptoms of ascariasis are usually vague or nonspecific, the radiologist may be in a position to play a major role in the proper diagnosis of this disease.


NANOMEDICINE: will it offer possibilities to overcome multiple drug resistance in cancer?
This review is written with the purpose to review the current nanomedicine literature and provide an outlook on the developments in utilizing nanoscale drug constructs in treatment of solid cancers as well as in the potential treatment of multi-drug resistant cancers. No specific design principles for this review have been utilized apart from our active choice to avoid results only based on in vitro studies. Few drugs based on nanotechnology have progressed to clinical trials, since most are based only on in vitro experiments which do not give the necessary data for the research to progress towards pre-clinical studies. The area of nanomedicine has indeed spark much attention and holds promise for improved future therapeutics in the treatment of solid cancers. However, despite much investment few targeted therapeutics have successfully progressed to early clinical trials, indicating yet again that the human body is complicated and that much more understanding of the fundamentals of receptor interactions, physics of nanomedical constructs and their circulation in the body is indeed needed. We believe that nanomedical therapeutics can allow for more efficient treatments of resistant cancers, and may well be a cornerstone for RNA based therapeutics in the future given their general need for shielding from the harsh environment in the blood stream.


The Karolinska KI/K COVID-19 Immune Atlas: An open resource for immunological research and educational purposes.
The Karolinska KI/K COVID-19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS-CoV-2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response towards SARS-CoV-2 infection in humans, as it occurred during the first wave. The Immune Atlas was built as an open resource for broad research and educational purposes. It contains a presentation of the response evoked by different immune and inflammatory cells in defined naïve patient-groups as they presented with moderate and severe COVID-19 disease. The present Resource Article describes how the Karolinska KI/K COVID-19 Immune Atlas allow scientists, students, and other interested parties to freely explore the nature of the immune response towards human SARS-CoV-2 infection in an online setting.


Mutations in alpha-chain of C4BP that selectively affect its factor I cofactor function.
C4b-binding protein (C4BP) inhibits all pathways of complement activation, acting as a cofactor to the serine protease factor I (FI) in the degradation of activated complement factors C4b and C3b. C4BP is a disulfide-linked polymer of seven alpha-chains and a unique beta-chain, the alpha- and beta-chains being composed of eight and three complement control protein (CCP) domains, respectively. In previous studies we have localized cofactor activity and binding of C4b to alpha-chain CCP1-3 of C4BP, whereas the binding of C3b required additionally CCP4. Likewise, introduced point mutations that decreased binding of C4b/C3b caused a decrease in cofactor activity. In the present study, we describe two mutants of C4BP, K126Q/K128Q and F144S/F149S, clustered on alpha-chain CCP3, which selectively lost their ability to act as cofactors in the cleavage of both C4b and C3b. Both mutants show the same binding affinity for C4b/C3b as measured by surface plasmon resonance and have the same inhibitory effect on formation and decay of the classical pathway C3-convertase as the wild type C4BP. It appears that C4b and C3b do not undergo the same conformational changes upon binding to the C4BP mutants as during the interaction with the wild type C4BP, which then results in the observed loss of the cofactor activity.


Quantitative magnetic resonance imaging of 'Fuyu' persimmon fruit during development and ripening.
Qualitative and quantitative proton magnetic resonance imaging techniques were applied to persimmon (Diospyros kaki cv 'Fuyu') fruit during development and post-harvest ripening. Spin-lattice (T(1)) relaxation times in mesocarp parenchyma and vascular tissue exhibited a sigmoidal pattern of increase leading to commercial harvest, but declined abruptly during ripening, 2.5 weeks after picking. T(1) times in parenchyma tissue were 1000 and 2100 ms in fruitlets, and at commercial harvest, respectively. T(1) times in vascular tissue were consistently shorter than those in parenchyma tissue by 300 to 600 ms. In contrast, spin-spin (T(2)) relaxation varied over a narrow range during development, i.e., 82 to 106 ms, and 59 to 73 ms, for parenchyma and vascular tissue, respectively. During ripening, T(2) measurements increased smoothly, commencing one week after harvest. Dry matter, water content, skin color, water-soluble tannins, soluble solids, and mineral and carbohydrate composition was also determined in companion fruit. No obvious associations linking physico-chemical and MR parameters were established, implying that the changes in relaxation measurements observed in 'simple' fruit systems can not be rationalised without recourse to more complex investigations involving SEM and different NMR spectroscopic and imaging techniques.


Custom-made laser-welded titanium implant prosthetic abutment.
A technique to create an individually modified implant prosthetic abutment is described. An overcasting is waxed onto a machined titanium abutment, cast in titanium, and joined to it with laser welding. With the proposed technique, a custom-made titanium implant prosthetic abutment is created with adequate volume and contour of metal to support a screw-retained, metal-ceramic implant-supported crown.


Articles on hemorrhagic shock published between 2000 and 2021: A CiteSpace-Based bibliometric analysis.
To conduct a bibliometric analysis of literature on hemorrhagic shock published between 2000 and 2021 with the help of Citespace to explore the current status, hotspots and research trends in this regard, with the results presented in a visualized manner. The data over the past 22 years were retrieved from the Web of Science (WOS) Core Collection database and downloaded as the "Full Record and Cited References". Cooperative analysis, cluster analysis, co-citation analysis, and burst analysis were performed based on the data on countries/regions, institutions, journals, authors, and keywords through Citespace. A total of 2027 articles were retrieved. The number of annual publications fluctuated but was generally on an upward trend. The United States stands out as the most productive country (989 articles), the University of Pittsburgh the most productive publishing institution (109 articles), SHOCK the most cited journal (1486 articles), TAO LI the most productive author (40 articles), DEITCH EA the most cited author (261 times of citation), hemorrhagic shock the most frequent keyword (725 times of occurrence), and "traumatic brain injury" the most covered article in keyword clustering (29 articles). The burst analysis revealed Harvard University as the institution with the highest strength value and the Journal of Trauma and Acute Care Surgery the most important journal. It was also concluded that HASAN B ALAM, AARON M WILLIAMS, and LIMIN ZHANG may continue to publish high-quality articles in the future. In the meanwhile, both "protect" and "transfusion" were considered the hotspots and trends in current research. The United States has been a major contributor to the publication of the articles over the past 22 years, with the most productive publishing institution, the most cited journal, and the most cited author all coming from the US. Hemorrhagic shock, injury, resuscitation, trauma, models, activation, expression, fluid resuscitation, rats, and nitric oxide are hot topics in relevant research. According to the keyword burst analysis, the areas related to "protect" and "transfusion" may rise as the research directions in the future. However, since the hotspots in the research of hemorrhagic shock are short-lived and fast-changing, the researchers should pay more attention to the development trend in this field.


Sports Sponsorship as a Cause of Obesity.
This article investigates the role of food and beverage sponsorship of sports in influencing dietary behaviour, and ultimately obesity, focusing on research published in the past 5 years. A systematic strategy was used to search the health science, social science and marketing databases to identify peer-reviewed literature on food and non-alcoholic beverage company sponsorship of sport published in English from 2015 to 2019. Sixteen discrete studies were identified: six content analyses, two qualitative studies, four cross-sectional surveys and four experimental studies. Findings indicate sports sponsorship is widely used to promote unhealthy foods through professional and community sport, prompting increased awareness and preference for sponsor products. Most studies assessed self-reported responses to sponsorship, with a lack of behavioural data on food purchasing and consumption. Sports sponsorship by unhealthy food brands achieves vast population reach and exposure, promoting increased brand awareness and preference for sponsor products. Research is needed to improve our understanding of the relationship between food and beverage sponsorship and energy intake. Research evaluating the efficacy of strategies to reduce spectator's exposure to unhealthy sports sponsorship is also needed.


The link between bipolarity and substance use: A controlled clinic based study.
Because of high rates of co-occurrence, common familial risk, and phenotypic similarities, we conjectured that substance use and bipolar disorder might have a common substrate of origin in bipolarity and that they might lie on a continuum of bipolarity. Thus it was aimed to investigate the association between bipolarity and substance use through a controlled, clinic based study. Cross sectional assessment and comparison of bipolarity as trait in four groups, namely the substance use disorder (SUD), bipolar disorder (BPAD), dual diagnosis (DD), and the healthy control (HC) groups. Bipolar spectrum diagnostic scale (BSDS) was used. The quality of life in these four groups was also assessed using WHOQOL-Bref scale. The mean Bipolar spectrum diagnostic scale (BSDS) score in SUD was 11.0 ± 5.3 which was more than that of HC (6.2 ± 3.9) and lesser than that in BPAD (18.4 ± 4.2) and DD (20.6 ± 3.6). Differences among all four groups were statistically significant. SUD group was found to have significantly higher score than healthy control. The BSDS score of DD and BPAD groups were higher than those of SUD but the difference between BPAD and DD was non-significant. The results showed a potential association between substance dependence and bipolarity. Mood dysregulation appears to be the link between the two. The gradient of bipolarity detected by BSDS screener suggests a continuum model between substance use and bipolar disorder. However, this is a clinic based study and only male patients have been taken for study.


Circulating retinol and 25(OH)D contents and their association with symptoms in children with chronic tic disorders.
The present study measured serum levels of vitamin A (VA) and vitamin D (VD) in children with chronic tic disorders (CTD) and investigated their potential association with CTD and comorbidity of attention deficit hyperactivity disorder (ADHD) and the association of their co-insufficiencies or deficiencies with CTD symptoms. A total of 176 children (131 boys and 45 girls, median age of 9 years) with CTD were recruited as the CTD group. During the same period, 154 healthy children were selected as the healthy control (HC) cohort. Circulating retinol and 25-hydroxyvitamin D (25[OH]D) levels were measured for all participants using high-performance liquid chromatography (HPLC) and tandem mass spectrometry. The Yale Global Tic Severity Scale (YGTSS) was employed for the assessment of tic status and CTD impairment. The Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were used to evaluate comorbidity symptoms. CTD pediatric participants exhibited markedly diminished circulating retinol and 25(OH)D levels compared to HCs. Moreover, VA and VD deficiencies and their co-insufficiencies/deficiencies were more prevalent in CTD participants than HCs. Circulating 25(OH)D levels were inversely proportional to the YGTSS motor tic scores. YGTSS scores in CTD children with only VA or VD insufficiency or deficiency or with VA and VD co-insufficiency/deficiency did not differ from those in CTD children with normal VA and VD. CTD children with comorbid ADHD displayed reduced circulating retinol and 25(OH)D concentrations and elevated prevalence of VD deficiency compared to CTD participants without comorbid ADHD. Lower serum retinol content was intricately linked to the presence of elevated CTD and comorbid ADHD. VA and VD deficiencies and their co-insufficiencies/deficiencies were markedly enhanced in CTD pediatric participants compared to HCs. Lower VA concentration was linked to the presence of enhanced CTD and comorbid ADHD. Therefore, children with CTD, especially with comorbid ADHD, may be at a higher risk of VA or VD deficiency, which may prompt the clinicians to consider whether blood tests for VA and VD in CTD children would be helpful for clinical care.


Combined catheter thrombus fragmentation and fibrinolysis for acute pulmonary embolism.
The aim of this study is to evaluate the effectiveness and safety of combined catheter thrombus fragmentation and fibrinolysis for acute pulmonary embolism (PE). Forty-six patients (19 men and 27 women, average age 52.3 ± 13.4 years) with acute PE and right ventricular dysfunction were treated by mechanical thrombus fragmentation with a percutaneous transluminal coronary angioplasty guide catheter. Urokinase was injected into the culprit pulmonary artery after catheter thrombus fragmentation in all patients. Clinical success was achieved in all patients. After the treatment, the average pulmonary artery pressure was decreased from 57.2 ± 6.2 to 36.3 ± 4.1 mmHg (P < 0.01). The oxygen saturation rate was raised from 81.4 ± 4.3% to 97.0 ± 2.0% (P < 0.01), and the right ventricular function was improved. There was no in-hospital mortality and there were no major complications, such as haemorrhage. Patients were treated with warfarin for 6 months with no signs of PE recurrence during the follow up. In PE patients with right ventricular dysfunction and unstable haemodynamics, combined catheter thrombus fragmentation and thrombolysis appears to be a useful therapeutic strategy. In PE patients with right ventricular dysfunction and stable haemodynamics, randomized trials are still required to show that combination of catheter-directed thrombus fragmentation and thrombolysis is superior to standard anticoagulation.


Reasons for living, social support, and Afrocentric worldview: assessing buffering factors related to Black Americans' suicidal behavior.
This study utilized an ecological framework to explore the role of 4 culturally relevant protective factors-reasons for living, Afrocentric worldview, family support, and friend support-in protecting Black American college students from suicidal behavior. Participants were 289 Black American college students. We hypothesized that these 4 culturally relevant factors would exert indirect protective effects on suicidal behavior through their association with reduced depressive symptoms. Results indicated that reasons for living, perceived supportive behaviors from family, and Afrocentric worldview exerted indirect protective effects on suicidal behaviors through their negative associations with depressive symptoms. The mediation effect from friend support to depression and suicidal behavior was not significant.


Serotonin-2 receptors in the CNS of alcohol-preferring and -nonpreferring rats.
The densities of serotonin-2 (5-HT2) receptors, labelled with [3H]ketanserin (Ket), were examined in the CNS of alcohol-naive, adult, male alcohol-preferring (P) and -nonpreferring (NP) rats using quantitative autoradiography. The densities of binding sites labelled with 2.0 nM [3H]Ket were 15-25% lower (p < 0.05) in layer IV of the medial prefrontal, frontal, cingulate, parietal, and temporal cortices of the P line compared with the NP line. [3H]Ket binding in the P rats was also 40-50% lower (p < 0.05) in the medial and lateral nucleus accumbens, olfactory tubercle, and caudate-putamen, and 20% lower (p < 0.05) in the claustrum, compared with the NP line. No differences in 2.0 nM [3H]Ket binding were observed between the lines in the piriform cortex, hypothalamus, amygdala, hippocampus, ventral tegmental area, substantia nigra, central gray, and interpenduncular nucleus. Scatchard analysis of [3H]Ket binding (0.5-0.6 nM, determined in layer IV of the frontal and parietal cortex and in the lateral nucleus accumbens, indicated lower Bmax values without a change in Kd for the P compared to the NP rats. The results of this study indicate that there are fewer 5-HT2 receptors in certain CNS regions of the P relative to the NP rats.


Perception of body weight and self-reported eating and exercise behaviour among obese and non-obese women in Saudi Arabia.
A case control study was conducted to examine the theorized differences for eating and exercise behaviour among the obese and non-obese women from an urban health center in Saudi Arabia. Perceptions regarding actual and ideal body size were also determined. The obese were significantly more likely to eat under emotional conditions of stress and anger, in secrecy, and indulge in binge eating (P < 0.05). Frequent snacking and drinking of regular soda drinks was also more common in this group compared to the controls (P < 0.05). A weak association was observed for nibbling at food without being aware and preference of sweet foods compared to savoury ones by the obese (P < 0.1). A large group of the study population (75%) were either not exercising at all or doing so infrequently--a feature expected in the middle and lower social class group of women in this region. A sizable proportion of women either overestimated (28.6%) or underestimated (28.9%) their actual body weight with increasing education significantly related to overestimation of weight and vice versa (P < 0.05). A change in the concept of an ideal body image from the overweight female to that of the slim figure was also observed with advancing education. To control and prevent obesity in this region, it is suggested that health education related to an awareness of a healthy body size and appropriate eating and exercise behaviour should be given through primary health centers, other health facilities and schools.


Assembling complex genotypes to resist Fusarium in wheat (Triticum aestivum L.).
Fusarium head blight of wheat is a major deterrent to wheat production world-wide. The genetics of FHB resistance in wheat are becoming clear and there is a good understanding of the genome location of FHB resistance QTL from different sources such as Sumai3, Wuhan, Nyubai and Frontana. All the components needed for assembling complex genotypes through large-scale molecular breeding experiments are now available. This experiment used high throughput microsatellite genotyping and half-seed analysis to process four independent crosses through a molecular breeding strategy to introduce multiple pest resistance genes into Canadian wheat. This included two backcrosses and selection for a total of six FHB resistance QTL, orange blossom wheat midge resistance (Sm1) and leaf rust resistance (Lr21). In addition, the fixation of the elite genetic background was monitored with 45-76 markers to accelerate restoration of the genetic background at each backcross. The strategy resulted in 87% fixation of the elite genetic background on average at the BC2F1 generation and successfully introduced all of the chromosome segments containing FHB, Sm1 and Lr21 resistance genes. The molecular breeding strategy was completed in 25 months, at an equal pace to conventional crossing and selection of spring wheat.


Albumin uptake by renal lymphatics with and without obstruction of the renal vein.
Experiments involving injection of radio-iodinated albumin into the left renal arteries or left ureters of dogs indicate that the renal lymphatics are capable of a major contribution in returning to the circulation albumin (or other large molecules) escaping from renal capillaries. I131-albumin was injected into the jugular vein of controls or into the left renal artery or in retrograde manner into the left ureter of female dogs. Experimental groups included those with no obstruction, occlusion of left renal veins or left renal lymphatics, or both. Collections were made from the right femoral artery, both renal veins, thoracic duct and both ureters at frequent intervals for 2 to 4 hours. Data analysis included I131 concentration, specific activity, rate of recovery and selected ratios. After renal arterial injection, the percentage of I131 recovered in thoracic duct lymph of dogs without renal venous obstruction was 5 to 10 times that recovered in those that received injections into the jugular vein. In dogs with renal venous obstruction, recovery from the thoracic duct was 10 to 1,000 times that in control dogs. Most of the differences occurred during the first hour, after which time as recirculation and redistribution occurred the rates of appearance in thoracic duct lymph in each group were similar. The differences in the ratios of concentration in thoracic duct lymph to concentration in femoral arterial blood were also much greater when the renal vein was obstructed than in dogs with no obstruction. The greater return of albumin through the thoracic duct in those with impeded renal venous outflow was probably related to both sequestered concentration and increased intrarenal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


Intermittent preventive treatment and malaria amongst pregnant women who give birth at the Centre Hospitalier Régional Paul Moukambi de Koula-Moutou in southeastern Gabon.
Evaluating malaria control strategies for pregnant women is essential. The objective of this study was to determine the factors influencing antenatal care (ANC) visit attendance, complete intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and its impact on the health of pregnant women and their newborn babies living in semi-urban and rural areas of southeastern Gabon. This transversal study was performed at the Centre Hospitalier Régional Paul Moukambi de Koula-Moutou (CHRPMK). Information regarding age, frequency of prenatal consultations, obstetric history, use of malaria control measures, use of IPTp-SP, malaria diagnostic of women and their newborns, were collected: (i): from birth registers from 1 January, 2018 to 31 December, 2019 and, (ii): a questionnaire from January to April 2020. In total, 1,851 and 323 pregnant women were included during the first and the second sub-set of study, respectively. In the first sub-set of data, the mean age was 26.18 ± 7.02 years and 96.54% (1,787/1,851) of pregnant women had attended ANC service but 54.45% had complete ANC visit attendance (at least 4 ANC). The complete ANC visit was linked with age (p < 0.001) and profession (p < 0.001). The complete IPTp-SP (at least 3 doses) was 58.87%. Complete IPTp-SP was linked to profession (aOR = 1.49, 95% CI [1.04-2.18], p < 0.001), ANC visit (aOR = 0.176, 95% CI [0.14-0.22], p < 0.034) and age (p = 0.03). Birth weight was higher for babies whose mothers had received complete IPTp-SP (p < 0,001) but the Apgar score was not influenced by the use of IPTp-SP (p = 0.71). In the second sub-set of data, the prevalence of plasmodial infection was 3.10% (95% IC [1.21-5]) and Plasmodium falciparum was responsible for 100% of infections. The prevalence of plasmodial infection was the same for all age groups (p = 0.69), gravidity (p = 0.13) and domestic control measures (p > 0.05). A low birth weight was statistically linked to the mother's plasmodial infection (p < 0.01). Furthermore, plasmodial infection was statistically linked to premature birth (p < 0.001). It was observed that attendance of women to ANC service and a complete IPTp-SP course is insufficient.


Effect of protamine sulfate on antithrombin III activity.
When protamine sulfate was added to heparinized plasma in vitro for neutralization of heparin, the activities on both thrombin and Xa known as heparin cofactor in antithrombin action were completely abolished. However, progressive activities on thrombin and Xa both recovered within 30 minutes after protamine sulfate addition. When equivalent heparin was again added, heparin cofactor activity was immediately restored. Based on the fact that protamine sulfate did not show any direct action on the antithrombin III molecule, the presence of AT III with progressive activity was considered to play an important role in the rebound phenomenon of heparin after heparin neutralization with protamine sulfate.


The effect of immunosuppressants and adoptive transfer in monocrotaline pyrrole pneumotoxicity.
Monocrotaline pyrrole (MCTP) is a pyrrolizidine alkaloid that causes pulmonary vascular injury and pulmonary hypertension in rats. The lesions in lungs of MCTP-treated rats are similar to those occurring in humans with primary pulmonary hypertension. Thus, the MCTP-treated rat is a good animal model for this disease. The mechanisms by which MCTP causes lung injury are unknown. The character of the pulmonary lesions and the delay in onset of the injury after a single low dose of MCTP suggest that immune mechanisms may be important in the pathogenesis. Accordingly, rats were treated with MCTP and the immunosuppressants antilymphocyte serum (ALS) or cyclosporin A (CyA). Neither ALS nor CyA completely protected rats from the injury due to MCTP. Several series of experiments also were undertaken to assess the effect of lymphocytes adoptively transferred from MCTP-treated donor rats into MCTP-treated recipient rats. Adoptive transfer of lymphocytes did not decrease the onset time of the injury or increase the severity of lesions due to MCTP in the recipients. These results indicate that immune mechanisms are probably not involved in MCTP-induced pulmonary injury.


A Novel Technique for Thyroplasty Type 1, With Prolene Mesh Implant.
To analyze the efficacy of a modified approach to thyroplasty type one using prolene mesh implant. Interventional study. Combined Military Hospital Kharian, Pakistan, in Ent department, from July 2020 to Jan 2021. Medialization thyroplasty with prolene mesh was performed on the patients satisfying the inclusion criteria. They were analyzed objectively as well as subjectively in terms of Mean Maximum phonation time, maximum word count, and visual analog score about the quality of voice. Data analysis was done with SPSS version 20. Pre-operative and post-operative records were compared using paired sample t-test. A total of 39 patients underwent vocal cord medialization with prolene mesh implant. The Mean age for medialization was 41.09 + 13.37. 23 patients were females and 15 were males. 26 patients had unilateral and 13 patients had bilateral vocal dysfunction. 18 of them had vocal dysfunction due to thyroidectomy, eight had idiopathic causes and 13 had miscellaneous. The improvement in mean visual analog score was 2.87 postoperatively. Median maximum phonation time increased about five seconds postoperatively, seven seconds in males, and 4.5 seconds for females. The maximum word count increased from 11.33 preoperatively to 18.28 postoperatively. There were no major complications observed in our study. These results were comparable to many other studies for vocal cord medialization with different implant materials. But prolene mesh implant offers an easily available yet cost-effective alternative with similar benefits. III (Treatment benefits: Non-randomized controlled cohort/follow-up study).


Study on the real-time object detection approach for end-of-life battery-powered electronics in the waste of electrical and electronic equipment recycling process.
With the growing use of electrical and electronic equipment (EEE), managing end-of-life EEE has become critical. Thus, the demand for sorting and detaching batteries from EEE in real time has increased. In this study, we investigated real-time object detection for sorting EEE, which using batteries, among numerous EEEs. To select products with batteries that have been mainly recycled, we crowd-sourced and gathered about 23,000 image datasets of the EEE with battery. Two learning techniques-data augmentation and transfer learning-were applied to resolve the limitations of the real-world data. We conducted YOLOv4-based experiments on the backbone and the resolution. Moreover, we defined this task as a binary classification problem; therefore, we recalculated the average precision (AP) scores from the network through postprocessing. We achieved battery-powered EEE detection scores of 90.1% and 84.5% at AP scores of 0.50 and 0.50-0.95, respectively. The results showed that this approach can provide practical and accurate information in the real world, hence encouraging the use of deep learning in the pre-sorting stage of the battery-powered EEE recycling industry.


Stress hyperglycaemia is associated with poor functional outcomes in patients with acute ischaemic stroke after intravenous thrombolysis.
Transient hyperglycaemia in the context of illness with or without known diabetes has been termed as 'stress hyperglycaemia'. Stress hyperglycaemia can result in poor functional outcomes in patients with acute ischaemic stroke (AIS) who underwent mechanical thrombectomy. We investigated the association between stress hyperglycaemia and clinical outcomes in AIS patients undergoing intravenous thrombolysis (IVT). We examined 666 consecutive patients with AIS who underwent IVT from 2006 to 2018. All patients had a glycated haemoglobin level (HbA1c) and fasting venous blood glucose measured within 24 h of admission. Stress hyperglycaemia ratio (SHR) was defined as the ratio of the fasting glucose to the HbA1c. Univariate and multivariate analyses were employed to identify predictors of poor functional outcomes (modified Rankin Scale 3-6 at 3 months) after IVT. Three-hundred and sixty-one patients (54.2%) had good functional outcomes. These patients tended to be younger (60.7 ± 12.7 vs. 70 ± 14.4 years, P < 0.001), male (70.7% vs. 51.5%, P < 0.001), had lower prevalence of atrial fibrillation (13.0% vs. 20.7%, P = 0.008) and lower SHR (0.88 ± 0.20 vs. 0.99 ± 26, P < 0.001). Patients with high SHR (≥0.97) were slightly older than those with low SHR (<0.97) and were more likely to have diabetes mellitus. On multivariate analysis, higher SHR was independently associated with poor functional outcomes (adjusted odds ratio 3.85, 95% confidence interval 1.59-9.09, P = 0.003). SHR appears to be an important predictor of functional outcomes in patients with AIS undergoing IVT. This may have important implications on the role of glycaemic control in the acute management of ischaemic stroke.


Assessment of functional tag single nucleotide polymorphisms within the DRD2 gene as risk factors for post-traumatic stress disorder in the Han Chinese population.
Gene variations related to the dopaminergic pathway have been implicated in a number of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). Dopamine D2 receptor (DRD2) has been shown to significantly contribute to neuropsychiatric disorders and may specifically contribute to predisposition to PTSD. This study aimed to evaluate the association of polymorphisms within the entire DRD2 gene with PTSD in a case-control study. A total of 834 unrelated Han Chinese adults, including 497 healthy volunteers and 337 patients with PTSD, were used in this study. Fifteen tag single-nucleotide polymorphisms (tSNPs) were selected spanning the entire DRD2 gene through the construction of haplotype bins. Genotypes were gathered using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic frequencies and clinical characteristics were compared in two independent Han Chinese populations. Moreover, the functionality of the rs2075652 and rs7131056 polymorphisms were assessed by measuring transcriptional enhancer activities. Fifteen tag SNPs were identified in the Han Chinese population and all were common SNPs. Among 15 tSNPs, two of them (rs2075652 and rs7131056) significantly associated with PTSD. PTSD individuals were more likely to carry the rs2075652A and rs7131056A allele compared to the controls (P<0.05). The haplotype GTGATCGCGCAGGCG, had a risk effect on PTSD occurrence (OR=1.75, 95% CI: 1.24-2.48, P=0.002). Additionally, the rs2075652 polymorphism contained intronic enhancer activities. The rs2075652 and rs7131056 polymorphisms, and the haplotype GTGATCGCGCAGGCG within the DRD2 gene, may be potential markers to predict susceptibility to PTSD.


Purification and properties of aldehyde reductases from human placenta.
Aldehyde reductases (alcohol: NADP+-oxidoreductase, EC 184.108.40.206) I and II from human placenta have been purified to homogeneity. Aldehyde reductase I, molecular weight about 74 000, is a dimer of two nonidentical subunits of molecular weights of about 32 500 and 39 000, whereas aldehyde reductase II is a monomer of about 32 500. Aldehyde reductase I can be dissociated into subunits under high ionic concentrations. The isoelectric pH for aldehyde reductases I and II are 5.76 and 5.20, respectively. Amino acid compositions of the two enzymes are significantly different. Placenta aldehyde reductase I can utilize glucose with a lower affinity, whereas aldehyde reductase II is not capable of reducing aldo-sugars. Similarly, aldehyde reductase I does not catalyse the reduction of glucuronate while aldehyde reductase II has a high affinity for glucuronate. Both enzymes, however, exhibit strong affinity towards various other aldehydes such as glyceraldehyde, propionaldehyde, and pyridine-3-aldehyde. The pH optima for aldehyde reductases I and II are 6.0 and 7.0, respectively. Aldehyde reductase I can use both NADH and NADPH as cofactors, whereas aldehyde reductase II activity is dependent on NADPH only. Both enzymes are susceptible to inhibition by sulfhydryl group reagents, aldose reductase inhibitors, lithium sulfate, and sodium chloride to varying degrees.


Optimisation of hepatocellular carcinoma surveillance in patients with viral hepatitis: a quality improvement study.
Surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasound is a standard of care for higher-risk patients with viral hepatitis. Adherence to screening guidelines is an important quality indicator in hepatology, but multiple studies have demonstrated poor HCC surveillance practices in real-world settings. The aim of this project was to audit and then optimise HCC surveillance of viral hepatitis patients, who fulfilled criteria for screening, associated with a large tertiary hospital. Clinical practice improvement principles were utilised. A baseline audit of 22 consecutive viral hepatitis patients was performed. Major barriers preventing adequate surveillance were identified and three interventions to improve adherence to guidelines were introduced. These included: improved doctor education, system redesign and improved patient education. The effects of interventions were measured by serial random audits of patients. A final audit occurred over 3 years after the initial baseline audit. At baseline, 46% and 0% of patients had appropriate surveillance performed during the prior 6 months (one surveillance cycle) and 2 years (four surveillance cycles) respectively. Three years after initiation of these strategies, a final audit revealed 92% (vs 46% at baseline) and 64% (vs 0% at baseline) of patients had appropriate HCC surveillance performed during the preceding 6 months and 2 years intervals respectively (P < 0.001 in each case). Simple and low-cost interventions can considerably improve the clinical effectiveness of HCC screening programmes in real world settings. Clinical practice improvement principles appear to be a valid methodology for achieving this positive change.


Determination of zearalenone and its metabolites in urine samples by liquid chromatography with electrochemical detection using a carbon nanotube-modified electrode.
A simple and sensitive method for the separation and determination of zearalenone (ZON) and its secondary metabolites, namely beta-zearalenol (beta-ZAL), beta-zearalanol (beta-ZOL), alpha-zearalenol (alpha-ZAL), alpha-zearalanol (alpha-ZOL) and zearalanone (ZAN) in urine (human, bovine and swine) samples is proposed. The method comprises previous clean-up and pre-concentration on C(18) adsorption cartridges of the analytes followed by liquid chromatographic separation and direct electrochemical detection at +0.85mV using a carbon nanotube-modified glassy carbon electrode (CNT-GCE). This method allows the determination of beta-ZAL, beta-ZOL, alpha-ZAL, alpha-ZOL, ZAN and ZON in a linear range between 5 and 50ngmL(-1), with relative standard deviation values lower than 6.9% (intra-day) and 7.1% (inter-day), in all cases. Detection limits ranging between 1.3ngmL(-1) (beta-ZOL, alpha-ZAL, alpha-ZOL) and 1.4ngmL(-1) (beta-ZAL, ZAN, ZON) were achieved. The usefulness of the proposed method was demonstrated by the analysis of spiked and natural samples of human, bovine and swine urine samples.


Speech-evoked auditory brainstem response; electrophysiological evidence of upper brainstem facilitative role on sound lateralization in noise.
Sound lateralization/localization is one of the most important auditory processing abilities, which plays approved role in auditory streaming and speech perception in challenging situations like noisy places. In addition to the main role of lower brainstem centers like superior olivary complex in sound lateralization, efferent auditory system effects on improving auditory skills in everyday auditory challenging positions were revealed. This study evaluated noise effects on lateralization scores in correlation with an objective electrophysiologic test (Speech-ABR in noise), which objectively shows cumulative effects of the afferent and efferent auditory systems at the inferior colliculus and upper brainstem pathway. Fourteen normal-hearing subjects in the age range of 18 to 25 participated in this study. Lateralization scores in the quiet and noisy modes were evaluated. Speech-ABR in both ears for quiet mode and three different contralateral noise levels (SNR = + 5, 0, - 5) were recorded, too. Correlation of lateralization scores and Speech-ABR changes in noise was studied. Significant decrease of lateralization scores with latency increase and amplitude decrease of Speech-ABR transient peaks (V, A, O) was seen with noise presentation. A high positive correlation between lateralization decrease with latency increase of onset peaks (V, A) and amplitude decrease of transient peaks (V, A, O) was found in low signal-to-noise ratios. The study revealed that in high challenging auditory situations like auditory lateralization in noise, upper brainstem centers and pathways play a facilitative role for main auditory lateralization centers in lower levels.


Registry Data-Valuable Lessons But Beware the Confounders.
A mature national joint registry with widespread adoption and audit can successfully demonstrate trends and influence future orthopedic practice. Correlations can be identified; however, this should not be misinterpreted as causality. It is essential to consider confounding when analyzing observational datasets.