Minimally invasive approach versus traditional open approach for one level posterior lumbar interbody fusion.
While over the last ten years minimally invasive posterior lumbar interbody fusion (PLIF) has been acknowledged to (i) reduce approach-related morbidity associated with quicker recovery, (ii) require a shorter hospital stay and (iii) deliver similar clinical outcomes when compared to a traditional approach, it is still not the current gold standard. In order to demonstrate the efficacy of the minimally invasive lumbar PLIF approach, a retrospective study was conducted comparing both approaches. A retrospective study was conducted with 40 patients treated for one level, degenerative lumbar instability. 20 patients received lumbar PLIF though a standard open approach, while another 20 underwent a minimally invasive approach using the "SpiRIT"-system. Spinal pathological features, stabilized segments, number of implanted pedicle screws, surgical time, radiation time, blood loss, complications, radiographic images and standardized patient questionnaires (VAS, ODI) were evaluated. The follow-up period was one year. One year after the performed surgery, we found no significant difference between the two groups with regard to clinical and radiographic outcome. However, in the minimally invasive group we noticed less blood loss, less postoperative pain, a shorter recovery time and a shorter hospital stay. Despite these benefits, the minimally invasive group also experienced a longer surgical and radiation time as compared to the "open" group. This study confirmed the results of previous studies which advocated the advantages of less blood loss, less postoperative pain, quicker recovery and shorter duration of hospitalization. However, in the long run, one year after surgery, both groups showed no significant difference with regards to clinical and radiographic outcome. Therefore long-term controlled studies are necessary to validate the role of the minimally invasive PLIF in degenerative lumbar instability.


End-User Input into the Design and Validation of a Synthetic Thoracoscopic Esophageal Atresia/Tracheo-Esophageal Fistula Simulator.
Introduction: Thoracoscopic repair of esophageal atresia and tracheo-esophageal fistula (EA/TEF) is challenging. We addressed this by designing a fully synthetic simulator of the procedure and described the design process and how its content validity was assessed. Methods: An iterative design and assessment of content validity was undertaken in three stages. Data were collected from participants who trialed the model and completed a survey of their experience (adapted from Barsness et al.). Results: The model was trialed by participants of varying experience. Each design refinement improved the model's fidelity and validity. For the last iteration of the simulator, the observed averages (out of a maximum of 5) were: value as a training tool 4.8, relevance 4.6, physical attributes 4.5, realism of material 4.25, realism experience 4.17, and ability to perform tasks 3.77. Conclusion: An iterative design process based on end-user feedback has led to a synthetic simulator that has achieved a high level of content validity. This model has advantages over other EA/TEF simulators in that it is relatively inexpensive and does not use animal tissue, thus removing ethical and procurement issues. It was rated highly for its value and relevance to training.


[Clinical study on the effect of intra-arterial injection of mitoxantrone-lipiodol emulsion for hepatocellular carcinoma].
To investigate the effect of intra-arterial injection of mitoxantrone emulsified with ethiodized oil, forty-eight patients with hepatocellular carcinoma were evaluated. After the treatment, ten of the patients underwent hepatectomy. In the thirty-eight unresected cases, there were 15 (39%) partial responses, which continued 1.2 to 11.8 months (mean, 5.8 months). The 1- and 2- year survival rates were 67% and 38%, respectively. The response rate was higher in cases with tumor under 5 cm in diameter. In the remaining 10 resected cases, the necrotic areas in main nodules ranged from 65% to 100% (mean, 85%). This treatment might be applied effectively to patients with small hepatocellular carcinoma.


Are patients with positive screening but negative diagnostic test for gestational diabetes under risk for adverse pregnancy outcome?
Our aim was to determine the obstetrics outcomes of patients with positive 1-h glucose challenge test (GCT), but negative diagnostic test for gestational diabetes. Pregnancy records of 409 pregnants were reviewed. Patients were screened for gestational diabetes mellitus (GDM) with one-hour 50 g glucose challenge test (GCT) at 24-28 weeks of gestation. Patients with glucose challenge tests values > or = 130 mg/dL were refered for the 3 h, 100-g oral glucose tolerance test (OGTT). Positive GCT but negative for OGTT group (Group A) were compared retrospectively with the group of negative GCT (Group B) for obstetrics outcomes. GDM and impared glucose tolerance (IGT) were diagnosed in 33 (7.6%) and 46 (10.5%) patients, respectively. We identified 141 (34.4%) patients with positive GCT but negative for OGTT (Group A) and 189 (46.2%) patients with negative GCT (Group B). Gestational weight gain, polyhydramnios, family history of diabetes mellitus were significantly higher in group A than group B (P < 0.05). Prevalance of preterm labor, hypertension, cesarean delivery, mean birthweight, proportion of babies admitted to neonatal intensive care unit were similar in both groups. There are some differences for pregnancy outcomes between pregnants with positive GCT but negative for OGTT and negative GCT. These patients should be followed up carefully during the antepartum and intrapartum period.


A novel member of a zinc transporter family is defective in acrodermatitis enteropathica.
The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an approximately 3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as "hZIP4," which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc.


Circular hairs: nomenclature and meanings.
Trichoscopy has become an essential tool for the diagnosis of various diseases that affect the hair and scalp. Through dermatoscopy we identified a set of findings that share a circular shape of hair shafts. The objective of this study is to distinguish among the various forms of circular hairs in order to identify their peculiarities and to describe in which skin disorders they can be found.


Previous iodinated contrast anaphylaxis in blunt abdominal trauma: management options.
A 34-year-old man presented with significant intra-abdominal and orthopaedic injuries following a high-speed motorbike crash. The man had a history of an anaphylactic reaction to iodine. As a result, the gold standard CT of the abdomen with contrast was unable to be performed to ascertain the exact nature of the intra-abdominal injuries. After stabilisation, an MRI of the abdomen was performed which localised the injuries. The previous contrast anaphylaxis delayed full assessment of the patient and subsequent management. This case discusses the current literature and the management guidelines in a patient with previous anaphylaxis to contrast.


Dissolution of carbon dioxide bubbles and microfluidic multiphase flows.
We experimentally study the dissolution of carbon dioxide bubbles into common liquids (water, ethanol, and methanol) using microfluidic devices. Elongated bubbles are individually produced using a hydrodynamic focusing section into a compact microchannel. The initial bubble size is determined based on the fluid volumetric flow rates of injection and the channel geometry. By contrast, the bubble dissolution rate is found to depend on the inlet gas pressure and the fluid pair composition. For short periods of time after the fluids initial contact, the bubble length decreases linearly with time. We show that the initial rate of bubble shrinkage is proportional to the ratio of the diffusion coefficient and the Henry's law constant associated with each fluid pair. Our study shows the possibility to rapidly impregnate liquids with CO(2) over short distances using microfluidic technology.


Comparative studies of bile salts. 16-Deoxymyxinol, a second bile alcohol from hagfish.
1. Material containing the less polar sulphate previously noticed in hagfish bile salts gave, after dioxan-trichloroacetic acid cleavage, 16-deoxymyxinol [3beta,7alpha,-26(27)-trihydroxy-5alpha-cholestane]. 2. Anodic coupling of 3beta-hydroxy-5beta-cholanoic acid and the mixed half esters of dl-methylsuccinic acid, followed by lithium aluminium hydride reduction, yielded 3beta,26(27)-dihydroxy-5beta-cholestane. 3. 16-Deoxymyxinol, the third known bile alcohol having the 3beta-hydroxy-5alpha-hydrogen configuration, poses again the question of how the 3beta-hydroxyl group of cholesterol can be ;retained' in biosynthesis of primitive bile salts.


Glucose disappearance rate, insulin response and growth hormone response in the small for gestational age and premature infant of very low birth weight.
The purpose of the present investigation was to study the disappearance rate of intravenously administered glucose, plasma insulin, plasma growth hormone (GH) and their responses to an intravenous glucose load in 29 infants who were small for gestational age (SGA). The findings were compared to those in 19 premature babies of similar birth weight who were appropriate for gestational age (AGA); in all the weights were below 2,000 g. The babies were divided in two groups according to their age when tested, at less than 24 and 25-48 h. SGA infants cleared glucose more rapidly than AGA infants (p less than 0.01) whose clearance rates were similar to those previously reported in normal full-size and full-term newborns. Arterial insulin values before glucose loading were similar in all groups. The insulin response to glucose was poor in both SGA and AGA infants, but there was no significant difference between these two groups of infants. The response in the two groups at 24 and 25-48 h was similar. In 8 SGA babies insulin response was studied shortly after glucose injection to determine beta-cell release, but there was no significant difference of insulin level before and after glucose administration. In 5 AGA and 8 SGA babies insulin response was studied simultaneously in portal vein and aorta. In AGA babies the insulin response was completely different in the two vessels with a high response in the vein; on the contrary, in SGA infants response was variable. Growth hormone levels were high before test in SGA and AGA; after a glucose load the plasma GH levels increase, but the response was identical in SGA and AGA.


Bariatric surgery: a cutting-edge cure for Type 2 diabetes?
Type 2 diabetes is rapidly becoming a global health crisis. It is associated with multiple comorbidities and is placing an ever increasing financial burden on society. There is now a need to explore new methods of tackling this problem. A growing pool of evidence suggests that bariatric surgery has the potential to cure Type 2 diabetes in a select population and provide additional benefits for many of its associated comorbidities. Whilst there are various proposals that explain these phenomena, current research suggests the cause is mainly due to increased post surgical release of insulin promoting gut hormones. The aim of this paper is to introduce some of the complex issues surrounding the use of bariatric surgery in Type 2 diabetes and highlight the controversial aspects encompassing this topic.


Effect of intravenous and oral pindolol on exercise tolerance and electrocardiographic changes in angina pectoris.
The effects of intravenous (0.4 mg) and oral pindolol (5 mg, t.i.d.) on exercise tolerance and electrocardiographic ST-segment changes were investigated in 20 patients with documented coronary artery disease (16 males and 4 females; mean age, 56.7 years). A randomized double-blind crossover design was used, and graded submaximal exercise was performed on a bicycle ergometer. Pindolol significantly decreased heart rate at rest, and during and after exercise. The time intervals before the appearance of ST depression, before anginal pain, and before the cessation of work were significantly increased after beta-adrenergic blockade, and work tolerance was enhanced, both indicating that pindolol is an effective antianginal agent. Angina appeared at a lower heart rate after pindolol. Anginal pain and cessation of work were associated with significantly less ST-segment depression after pindolol, suggesting that the relation between ST depression and myocardial ischemia is altered by beta-adrenergic blockade. The appearance and disappearance of ST-segment changes correlated closely with heart rate during placebo and pindolol treatment. Heart rate thus seems to be a major determinant of ST-segment depression during and after exercise in coronary artery disease.


In vitro Metabolism of Sodium 9-dehydro-17-hydro-andrographolide-19-yl Sulfate in Rat Liver S9 by Liquid Chromatography-Mass Spectrometry Method.
Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate (DHAS) is the active ingredient of Xiyanping injection, a traditional Chinese medicine in clinical use. However, there has been no report about the metabolic rate and metabolites of DHAS in vitro. In this article, DHAS was incubated with rat liver S9, and liquid chromatography/mass spectrometry (LC/MS) was used for the metabolism study. The residual concentrations of substrate were determined by ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for the metabolic rate study of DHAS in liver S9. Metabolites were identified by the (UPLC-TOF-MS(E)) Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry method. The calibration curves of DHAS were linear over the concentration range from 0.75 μM to 75.22 μM with correlation coefficients >0.99. The lower limit of quantification was 0.150 μM for DHAS. The determination recoveries of DHAS were in the range of 84.9-90.6%. The t½ and CLint of DHAS in rat liver S9 were 98.6 ± 2.1 min and 3.5 ± 0.1 mL/min/g, respectively. Five metabolites were preliminarily identified based on the high resolution mass spectrum data in comparison with related references. These metabolites were mainly the products of dehydration and hydrogenation of DHAS. The present in vitro metabolic study of DHAS provided valuable information about the metabolic rate and potential metabolites of DHAS, which are important for future in vivo metabolism studies of DHAS and the discovery of more active andrographolide derivatives. In this paper, sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate (DHAS) metabolism in vitro has been investigated with rat liver S9 using liquid chromatography-mass spectrometry (LC-MS). The result of quantitative analysis showed that DHAS had a long t1/2, which indicated its high metabolic stability. Five metabolites of DHAS were identified in the incubation system based on the high resolution mass spectrum data in comparison with related references, particularly dehydrated and hydrogenated products. The results would provide certain references to screen out more active andrographolide derivative for pre-clinically. Abbreviations used: MRM: Multiple reaction monitoring, DHAS: Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate, IS: Internal standard.


The novel mechanism of lenalidomide activity.
Lenalidomide acts by a novel drug mechanism-modulation of the substrate specificity of the CRL4(CRBN) E3 ubiquitin ligase. In multiple myeloma, lenalidomide induces the ubiquitination of IKZF1 and IKZF3 by CRL4(CRBN). Subsequent proteasomal degradation of these transcription factors kills multiple myeloma cells. In del(5q) myelodysplastic syndrome, lenalidomide induces the degradation of CK1α, which preferentially affects del(5q) cells because they express this gene at haploinsufficient levels. In the future, modulation of ubiquitin ligase function may enable us to target previously "undruggable" proteins.


Pneumonia caused by Candida krusei and Candida glabrata in a patient with chronic myeloid leukemia receiving imatinib mesylate treatment.
In this report we describe a patient suffering from chronic myeloid leukemia (CML), who was treated for 4.5 years with imatinib and developed pneumonia caused by two Candida species, i.e., C. krusei and C. glabrata. The patient was in complete hematologic remission and molecular analyses did not display the presence of TLR2-R752Q, TLR4-D299G and TLR4-T399I polymorphisms that may predispose individuals to fungal infections. This case report indicates that in some patients, as previously observed, the long-term administration of targeted therapy might affect immunity and predispose patients to opportunistic and life-threatening fungal infections.


Differential effect of insulin on saturated and unsaturated fatty acids.
Fatty acids fulfill important roles in physiology. The plasma concentrations of fatty acids are principally regulated by insulin, which suppresses the release of fatty acids from lipid stores, and catecholamines, which increase their release from lipid stores. Although insulin regulates the concentration of plasma free fatty acids (FFAs), little is known about the relative effects of insulin on the saturated compared with the unsaturated plasma fatty acids. In the current study, we specifically measured the plasma concentration of 3 saturated and 4 unsaturated fatty acids along with an estimate of lipolytic activity using a stable isotope of glycerol during a 3-hour, 1-step, euglycemic clamp study in humans. The data showed the expected decline in plasma fatty acids from 0.26 +/- 0.02 to 0.06 +/- 0.01 micromol/mL. Saturated fatty acids were reduced from 0.12 +/- 0.01 to 0.05 +/- 0.005 micromol/mL and unsaturated fatty acids were reduced from 0.11 +/- 0.01 to 0.01 +/- 0.001 micromol/mL after 3 hours of insulin infusion. At baseline, the ratio of saturated to unsaturated fatty acid was 55:45, which increased to 82:18 by the end of study. The changes in fatty acids were evident within 1 hour. Whole body lipolytic rates were measured with deuterated glycerol and decreased from 1.48 +/- 0.56 micromol x kg(-1) x min(-1) to 0.75 +/- 0.34 micromol x kg(-1) x min(-1). Baseline postabsorptive plasma fatty acid concentrations were significantly correlated to insulin sensitivity (M value) as measured during the euglycemic clamp. There were no significant differences between the more insulin-sensitive subjects when compared with the more insulin-resistant subjects with respect to the relative decreases in saturated and unsaturated fatty acids during insulin infusion. These data demonstrate a sustained differential effect of insulin on the plasma fatty acid profile.


Comparative genomic imprinting and expression analysis of six cattle genes.
Imprinted genes are monoallelically expressed in a parent-of-origin-specific manner under epigenetic regulation. Although it is generally believed that genomic imprinting is conserved among mammalian species, there is accumulating evidence that suggests such an assumption is false. Identification of species-specific imprinted genes is necessary to understand the evolution of genomic imprinting and to elucidate mechanisms leading to allele-specific expression. In this study, we analyzed the imprinting status of the CD81, target of antiproliferation antibody 1 (TSSC4), and oxysterol-binding protein homologue 1 (OBPH1) genes clustered on bovine chromosome 29; the paternally expressed gene 10 and ankyrin repeat and suppressor of cytokine signaling box-containing protein 4 genes clustered on bovine chromosome 4; and the 5-hydroxytryptamine (serotonin) 2A receptor microdomain gene on bovine chromosome 12 using a sequencing-based approach. It was found that CD81 and OBPH1 showed biallelic expression in all cattle tissues examined, whereas TSSC4 showed monoallelic expression in placental tissues, like its mouse ortholog. Comparative expression analysis showed that the imprinting pattern of the CD81, TSSC4, and OBPH1 cluster was not conserved among mouse, human, and cattle. None of these genes were imprinted in all 3 species. The the paternally expressed gene 10 gene was imprinted in all 3 species, whereas ankyrin repeat and suppressor of cytokine signaling box-containing protein 4 gene, reported to be imprinted in mouse, was not imprinted in cattle. The the 5-hydroxytryptamine (serotonin) 2A receptor gene was not imprinted in cattle, and human imprinting data has shown conflicting results. It is more likely that imprinting in the genes examined in this study is species-specific. In addition, we studied the expression and tissue distribution of transcripts of these genes in 174 fetal and adult cattle tissues.


Fluctuation of computed tomographic findings in white matter in Alexander's disease.
A Japanese boy developed febrile seizures and gait disturbance at 2 years of age and dysarthria a year later. He had generalized tonic-clonic seizures once or twice a year from the age of 4 years. Brain computed tomography (CT) showed symmetric low-density areas in the white matter of the frontal lobes. However, abnormal CT findings fluctuated occasionally, with no apparent change in clinical manifestations. Clinical evaluation at 9 years of age revealed hyper-reflexia, psychomotor retardation, megalencephaly, and slurred nasal speech. Magnetic resonance imaging showed white matter abnormalities, predominantly in the frontal lobes. He was a heterozygote of the Arg239Cys mutation of the glial fibrillary acidic protein gene and was diagnosed with Alexander's disease. Fluctuation of CT findings in white matter may reflect blood-brain barrier dysfunction in Alexander's disease.


TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF.
Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease.


The application of network scale up method on estimating the prevalence of some disabilities in the southeast of Iran.
More than a billion people have some form of disabilities worldwide. Persons living with a disability have many needs (including physically, mentally, and socially needs). Estimating the size of disabled population is a challenge in health systems. An innovative indirect method to estimate the size of populations is network scale up (NSU) having widely used for hidden populations. The method is based-on the social network of individuals. We assessed the capability of NSU to estimate persons living with a disability being a middle population (neither non-hidden nor hidden populations) in the Southeast of Iran (Kerman City, southeast Iran). A total of 3052 of Kermanian people over 20 year old were interviewed by simple random sampling. We asked them whether they knew acquaintances with complete blindness, severe visual impairment, deafness, severe hearing impairment, limb defects, and mental retardation, if yes; we wanted them to count them. Based on the network scale up method, the prevalence of the populations was estimated at 5.21/1000 in Kerman City where severe visual impairment was 1.35, mental retardation was 1.039, severe hearing impairment was 1.005, limb defects was 0.78, deafness was 0.59, and complete blindness was 0.56 (per 1000 inhabitants). The results were not exactly comparable to previous studies using different methods such as surveys. Although the method has some limitations, considering its easiness and cost-effectiveness, modified NSU could be used when direct methods are not practicable.


Near-infrared light-regulated cancer theranostic nanoplatform based on aggregation-induced emission luminogen encapsulated upconversion nanoparticles.
Photodynamic therapy (PDT) has been widely applied in the clinic for the treatment of various types of cancer due to its precise controllability, minimally invasive approach and high spatiotemporal accuracy as compared with conventional chemotherapy. However, the porphyrin-based photosensitizers (PSs) used in clinics generally suffer from aggregation-caused reductions in the generation of reactive oxygen species (ROS) and limited tissue penetration because of visible light activation, which greatly hampers their applications for the treatment of deep-seated tumors. Methods: We present a facile strategy for constructing a NIR-regulated cancer theranostic nanoplatform by encapsulating upconversion nanoparticles (UCNPs) and a luminogen (2-(2,6-bis((E)-4-(phenyl(40-(1,2,2-triphenylvinyl)-[1,10-biphenyl]-4-yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile, TTD) with aggregation-induced emission (AIEgen) characteristics using an amphiphilic polymer, and further conjugating cyclic arginine-glycine-aspartic acid (cRGD) peptide to yield UCNP@TTD-cRGD NPs. We then evaluated the bioimaging and anti-tumor capability of the UCNP@TTD-cRGD NPs under NIR light illumination in an in vitro three-dimensional (3D) cancer spheroid and in a murine tumor model, respectively. Results: With a close match between the UCNP emission and absorption of the AIEgen, the synthesized NPs could efficiently generate ROS, even under excitation through thick tissues. The NIR-regulated UCNP@TTD-cRGD NPs that were developed could selectively light up the targeted cancer cells and significantly inhibit tumor growth during the NIR-regulated PDT treatment as compared with the cells under white light excitation. Conclusion: In summary, the synthesized UCNP@TTD-cRGD NPs showed great potential in NIR light-regulated photodynamic therapy of deep-seated tumors. Our study will inspire further exploration of novel theranostic nanoplatforms that combine UCNPs and various AIEgen PSs for the advancement of deep-seated tumor treatments with potential clinical translations.


Rectus abdominis muscle endometriosis.
Endometriosis is characterized by an abnormal existence of functional endometrial tissue outside the uterine cavity, typically occuring within the pelvis of women in reproductive age. We report two cases with endometriosis of the abdominal wall; the first one in the rectus abdominis muscle and the second one in the surgical scar of previous caesarean incision along with the rectus abdominis muscle. Pre-operative evaluation included magnetic resonance imaging. The masses were dissected free from the surrounding tissue and excised with clear margins. Diagnosis of the excised lesions were verified by histopathology.


Neurochemical Systems of the Retina Involved in the Control of Movement.
Recent studies have revealed that the retina may exert control over deep brain function and may be importantly involved in the etiology, progression, and treatment of disorders such as Parkinson's disease (PD). While such a concept is uncharted territory and even less is known about the mechanism by which this might be achieved, this study was undertaken to determine how retinal dopamine (DA), serotonin (5-HT), and melatonin (MEL) neurotransmitter systems might be involved in the control of movement in their own right. To explore these further, intravitreal (IVIT) injections of DA, 5-HT, and MEL were made 0.5 or 3 h prior to testing horizontal and vertical movement in the open field as well as assessment on three motor tests used routinely to evaluate movement as a preclinical model of PD. The doses of DA (2 µl of 25 and 75 µg/µl), 5-HT (2 µl of 5 and 15 µg/µl), and MEL (2 µl of 5 µg/µl) were chosen because of previous work demonstrating an anatomically precise effect of these transmitters after they were injected directly into the brain. The postinjection times of testing were also chosen on the basis of previous intracerebral and IVIT work intimating the importance of the circadian cycle in determining the efficacy of such effects. 0.5 h after IVIT injection of DA at the 25 and 75 µg/µl doses, significant inhibition of motor function was observed. While IVIT injection of 10 or 30 µg of 5-HT also inhibited motor performance, this was significantly less than that seen with DA. In fact, IVIT injection increases motor performance compared to vehicle injection on some parameters. The IVIT injection of 10 µg of MEL facilitated motor function on many parameters compared to DA, 5-HT, and vehicle injection. When rats were tested 3 h after IVIT injection, the inhibition of vertical movement was also observed compared to controls. The present results illustrate that specific retinal neurotransmitter systems participate in the normal control of bodily motor function. The possible involvement of these systems in movement disorders such as PD is the subject of ongoing research.


Potential applications of artificial intelligence and machine learning on diagnosis, treatment, and outcome prediction to address health care disparities of chronic limb-threatening ischemia.
Chronic limb-threatening ischemia (CLTI) is the most advanced form of peripheral artery disease. CLTI has an extremely poor prognosis and is associated with considerable risk of major amputation, cardiac morbidity, mortality, and poor quality of life. Early diagnosis and targeted treatment of CLTI is critical for improving patient's prognosis. However, this objective has proven elusive, time-consuming, and challenging due to existing health care disparities among patients. In this article, we reviewed how artificial intelligence (AI) and machine learning (ML) can be helpful to accurately diagnose, improve outcome prediction, and identify disparities in the treatment of CLTI. We demonstrate the importance of AI/ML approaches for management of these patients and how available data could be used for computer-guided interventions. Although AI/ML applications to mitigate health care disparities in CLTI are in their infancy, we also highlighted specific AI/ML methods that show potential for addressing health care disparities in CLTI.


Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure.
The purpose of this study was to investigate whether long-term therapy with crataegus extract WS 1442 is efficacious as add-on therapy to preexisting diuretic treatment in patients with heart failure with a more advanced stage of the disease (New York Heart Association [NYHA] class III), whether effects are dose dependent, and whether the treatment is safe and well tolerated. Exercise capacity was assessed by use of seated bicycle ergometry with incremental workloads. Scores for subjective symptoms and complaints made by the patients were analyzed. Efficacy and tolerability of the treatments were judged by both the patients and investigators. Safety was assessed by the documentation of adverse events and the safety laboratory. A total of 209 patients were randomized to treatment with 1800 mg of WS 1442, 900 mg of WS 1442, or with placebo. After 16 weeks of therapy with 1800 mg of WS 1442 per day, maximal tolerated workload during bicycle exercise showed a statistically significant increase in comparison with both placebo and 900 mg of WS 1442. Typical heart failure symptoms as rated by the patients were reduced to a greater extent by WS 1442 than by placebo. This difference was significant for both doses of WS 1442. Both efficacy and tolerability were rated best for the 1800 mg of WS 1442 group by patients and investigators alike. The incidence of adverse events was lowest in the 1800 mg of WS 1442 group, particularly with respect to dizziness and vertigo. The data from this study confirm that there is a dose-dependent effect of WS 1442 on the exercise capacity of patients with heart failure and on typical heart failure-related clinical signs and symptoms. The drug was shown to be well tolerated and safe.


Independent Validation of a Self-Report Version of the IBD Disability Index (IBDDI) in a Population-Based Cohort of IBD Patients.
A new clinician-administered inflammatory bowel disease (IBD) Disability Index (IBDDI) was recently developed and validated among a population in France. We aimed to validate the IBDDI in a North American setting and adapt for use as a self-report tool. Persons 18-65 years old from the population-based University of Manitoba IBD Research Registry were mailed a self-administered survey. This survey included the IBDDI and several scales that should correlate with a disability measure- the World Health Organization (WHO) Disability Assessment Scale (WHODAS) 2.0, Work and Social Adjustment Scale (WSAS), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the K6-Kessler Emotional Distress Scale. We used Pearson correlation coefficients to assess construct validity, Cronbach's alpha to assess internal consistency, and Factor analysis to assess which of the IBDDI items likely belonged to a single IBD-related disability factor. In response to the survey request,1143 (46% of those contacted) participated (61% female, mean age 51, 52% with Crohn's disease). On an index scale from 0-100, 14% had a score ≥50 (extreme disability, 18% of those with Crohn's disease; 10% of those with ulcerative colitis). There were strong correlations between IBDDI and WSAS (0.76), WHODAS (0.76), K6 (0.73), and an inverse correlation with IBDQ (-0.86). The Cronbach's alpha was high (0.88). All but 2 items (number of liquid stools in the past week and arthritis/arthralgia) of the 14 identified for IBDDI loaded highly onto a single factor (factor loading > 0.40). The findings support the validity of this new self-report version of the IBDDI as a sound measure of disability in IBD.


Origins of growth stresses in amorphous semiconductor thin films.
Stress evolution during deposition of amorphous Si and Ge thin films is remarkably similar to that observed for polycrystalline films. Amorphous semiconductors were used as model materials to study the origins of deposition stresses in continuous films, where suppression of both strain relaxation and epitaxial strain inheritance provides considerable simplification. Our data show that bulk compression is established by surface stress, while a subsequent return to tensile stress arises from elastic coalescence processes occurring on the kinetically roughened surface.


Enantioselective construction of oxa- and aza-angular triquinanes through tandem [4 + 1]/[3 + 2] cycloaddition of sulfur ylides and nitroolefins.
A formal [4 + 1]/[3 + 2] cycloaddition sequence of sulfur ylides and alkene-tethered nitroolefins has been developed. The use of (R)-binol-derived chiral sulfide leads to an asymmetric process that allows the construction of oxa- and aza-angular triquinanes in good to excellent diastereo- and enantioselectivities.


Efficient small bandgap polymer solar cells with high fill factors for 300 nm thick films.
A high-molecular-weight conjugated polymer based on alternating electron-rich and electron-deficient fused ring systems provides efficient polymer solar cells when blended with C60 and C70 fullerene derivatives. The morphology of the new polymer/fullerene blend reduces bimolecular recombination and allows reaching high fill factors and power conversion efficiencies for films up to 300 nm thickness.


A genotype-independent real-time PCR assay for quantification of hepatitis B virus DNA.
Accurate quantification of hepatitis B virus (HBV) DNA levels is important for monitoring patients with chronic HBV infection and for assessing their responses to antiviral therapy. This study aimed to develop a real-time PCR assay that is sensitive and can accurately quantify a wide range of HBV DNA levels across the known HBV genotypes. An "in-house" real-time PCR assay using primers and a TaqMan probe in a highly conserved region of the HBV surface gene was designed. The assay was standardized against a WHO standard and validated against plasmids of HBV genotypes A through H. The linear quantification range was approximately 5 x 10(0) to 2.0 x 10(9) IU/ml. Results of samples from patients infected with HBV genotypes A through H tested using our real-time "in-house" PCR assay showed an excellent correlation with those of the Cobas Amplicor HBV Monitor (R2=0.9435) and the Cobas TaqMan HBV (R2=0.9873) tests. We have established a real-time PCR assay that is genotype independent and can accurately quantify a wide range of HBV DNA levels. Further studies of additional samples are ongoing to validate the genotype independence of our assay.


An Unusual Valence State: Trivalent Europium in Intermetallic Eu2 Ir3 Al9.
Eu2 Ir3 Al9 , synthesized from the elements in tantalum tubes, is one of the rare examples for trivalent europium in the field of intermetallic compounds. The compound crystallizes in the Y2 Co3 Ga9 -type structure (space group Cmcm), with lattice parameters fitting in between the isostructural samarium and gadolinium compounds. In the crystal structure, the Eu atoms form Al3 -triangle-centered honeycomb layers and exhibit a coordination number of 17 in the shape of a fivefold-capped hexagonal prism (Eu@Ir6 Al6 +Al5 ). Magnetic measurements indicate an overall low susceptibility, in line with van Vleck paramagnetism caused by the Eu3+ cations. Fits of the susceptibility yield a coupling constant of λ=290(10) K and an effective magnetic moment of μeff =4.56(1) μB , in line with a slight hybridization of the 7 F0 and 7 F1 state. 151 Eu Mössbauer spectroscopic investigations unambiguously prove the presence of solely Eu3+ in the bulk material.


The Response of the Pulp-Dentine Complex, PDL, and Bone to Three Calcium Silicate-Based Cements: A Histological Study in an Animal Rat Model.
The aim of this study was to histologically examine the tissue reaction of three different calcium silicate cements in the closure of perforations in rat incisor teeth. Material and Methods. An experimental lateral root perforation with pulp exposure was performed in 32 lower incisors of 16 male Wistar albino rats. They were randomly assigned into three test groups (each including eight teeth) that were filled either by Biodentine (BD) or MicroMega mineral trioxide aggregate (MM-MTA) or EndoSequence root repair material putty (ESRRM putty), besides eight unperforated incisors from the other four rats (control group). The inflammatory response and healing process were evaluated histologically and scored after one and four weeks. Differences among groups were tested by Kruskal-Wallis tests at P ≤ 0.05. In the first week, BD produced more inflammatory response in the pulpal (score 3) than other materials (score 2). Only ESRRM putty showed odontoblast-like cells in 50%, 25% dentine-like deposit, 25% evidence of bone deposition in the drilling site (score 2), and minimum periodontal ligament (PDL) necrosis and disorganization (25%, score 2). After one month, all groups had healthy pulpal tissue, but 25% of ESRRM putty retained score 1 inflammatory response, and 50% of the BD case had an incomplete palisading odontoblast layer (score 3). A thick and regular dentine bridge deposition was seen in the ESRRM putty group in comparison with MM-MTA and BD cases. The cortical plate healing in all ESRRM putty samples was complete (score 3), while an incomplete closure was seen in MM-MTA and BD groups (score 2). Both the MM-MTA and ESRRM putty groups had fully organized PDL (score 2), while in 50% of BD cases, a necrotizing area and disorganized PDL with inflammatory cells infiltration were still present. Statistically significant differences in the scores of any histologic parameters among the three tested materials were observed neither in the 1st nor in the 4th weeks of the experimental period. Better tissue compatibility and repair of pulpal and periodontal tissue have been detected after lateral perforation in the root of rat incisors when treated with ESRRM putty than MM-MTA and BD. However, the difference was not significant.


The Influence of Host Stress on the Mechanism of Infection: Lost Microbiomes, Emergent Pathobiomes, and the Role of Interkingdom Signaling.
Mammals constantly face stressful situations, be it extended periods of starvation, sleep deprivation from fear of predation, changing environmental conditions, or loss of habitat. Today, mammals are increasingly exposed to xenobiotics such as pesticides, pollutants, and antibiotics. Crowding conditions such as those created for the purposes of meat production from animals or those imposed upon humans living in urban environments or during world travel create new levels of physiologic stress. As such, human progress has led to an unprecedented exposure of both animals and humans to accidental pathogens (i.e., those that have not co-evolved with their hosts). Strikingly missing in models of infection pathogenesis are the various elements of these conditions, in particular host physiologic stress. The compensatory factors released in the gut during host stress have profound and direct effects on the metabolism and virulence of the colonizing microbiota and the emerging pathobiota. Here, we address unanswered questions to highlight the relevance and importance of incorporating host stress to the field of microbial pathogenesis.


Comparison of short- and mid-term outcomes of Italian- and German-speaking patients after an interdisciplinary pain management programme in Switzerland: A prospective cohort study.
To quantify and compare the course of health-related quality of life of immigrant native Italian-speaking and German-speaking patients before and after an interdisciplinary pain programme. Prospective cohort study with 1-12 month follow-up. Fibromyalgia, generalized widespread pain, and chronic non-specific back pain patients (Italian-speaking n = 96, German-speaking n = 199). Score changes measured with the Short Form 36 (SF-36) were compared with multivariate analysis using standardized mean differences (SMD), adjusted for sex, education and the baseline score. At baseline, health of the Italian-speaking patients was worse than for the German-speaking patients. Adjusted SMDs showed significantly better improvements in the German group compared with the Italian group: SF-36 Physical functioning SMD = 0.54 (at discharge) and 0.49 (at 12 months), General health SMD = 0.71 and 0.44, Vitality SMD = 0.43 and 0.48 in one sample. In the other sample, the corresponding SMDs were 0.06 (discharge), 0.50 (3 months) and 0.47 (6 months) for Bodily pain. State of health was better and health improvements were greater in German-speaking patients compared with Italian-speaking patients. Patients with a migration background may have special needs in therapeutic management, and addressing these might enhance the positive outcome in the short- and mid-term.


Membrane separation to improve degradation of road side grass by rumen enhanced solid incubation.
Membrane separation proved to be an excellent means to maintain high residence time of microorganisms in an anaerobic hydrolysis reactor, and relatively low concentration of hydrolysis products. The microbial biocommunity typical for the rumen environment could be maintained, and the reactor efficiency of the reactor improved. Less than 4 days were reqired to reach almost complete hydrolysis of the grass fed into the reactor. To avoid blocking of the membrane unit, a backwash system is necessary. The membranes needed to be backwashed every 20 min with 4 bar gas-pressure for 10 s. After this treatment the initial permeability was regained. The plant was operated with a flux of 12 ml h(-1) cm(-2) on average. The transmembrane pressure was in the range of 0.8-0.9 bar. 90% of the dissolved fatty acids permeated through the membrane.


Characterizing emission and breathing-zone concentrations following exposure cases to fluororesin-based waterproofing spray mists.
Measurements and simulations were performed to assess workers' exposure to solvent vapors and aerosols during the waterproofing of a tiled surface. This investigation followed two recent incidents in the same company where workers experienced acute respiratory illness after spraying a stain-repellent resin containing fluorinated polymers on stone-tiled walls and floors. Because the waterproofing activity had been done for years at the tile company without encountering any exposure problems prior to these cases, it was strongly suspected that the incidents were linked to a recent change in the composition of the coating mixture. Experimental measurements and simulations indicated that the emission rate of particles smaller than 10 microm may be estimated at 0.66 mg/sec (SD 0.10) for the old resin and at 0.37 mg/sec (SD 0.04) for the new one. The measurement of the solvent emission rate from surfaces coated with the two resins indicated that shortly after spraying, the emission was in the range of 18 to 20 mg/sec x m2 and was similar for both products. Solvent and overspray emission rates were introduced in a two-zone compartment model. The results obtained in the near-field indicate significant exposure to overspray mist (7 and 34 mg/m3 for new resin) and solvent vapors (80 to 350 ppm for the new resin). It was also shown that the introduction of the new resin tended to significantly decrease the levels of solvents and particulates in the workers' breathing zone. These results strongly suggest that cases of acute respiratory illness are related to the specific toxicity of the fluorinated polymer itself. The fact that the same polymer is used in various commercial products raises concern regarding other possible occupational and domestic exposures.


New machine learning method for image-based diagnosis of COVID-19.
COVID-19 is a worldwide epidemic, as announced by the World Health Organization (WHO) in March 2020. Machine learning (ML) methods can play vital roles in identifying COVID-19 patients by visually analyzing their chest x-ray images. In this paper, a new ML-method proposed to classify the chest x-ray images into two classes, COVID-19 patient or non-COVID-19 person. The features extracted from the chest x-ray images using new Fractional Multichannel Exponent Moments (FrMEMs). A parallel multi-core computational framework utilized to accelerate the computational process. Then, a modified Manta-Ray Foraging Optimization based on differential evolution used to select the most significant features. The proposed method evaluated using two COVID-19 x-ray datasets. The proposed method achieved accuracy rates of 96.09% and 98.09% for the first and second datasets, respectively.


Quantification of 5-FU in skin samples for the development of new delivery systems for topical cancer treatment.
5-Fluorouracil (5-FU) is used for the topical treatment of pre-cancerous skin lesions. However, previous reports focus on 5-FU quantification in plasma samples, failing to provide information about drug quantification in the skin. Therefore, the aim of this work was to develop a simple and reliable analytical method employing HPLC-UV for 5-FU quantification in skin samples. Chromatographic separation was obtained using the commonly available Lichrospher RP-C18 endcapped column. Porcine ear skin matrix-based analytical curves with thymine, as internal standard, were used. 5-FU was eluted at 5.2 min and thymine at 13.0 min. The method was selective, precise and accurate in the linear range from 0.3 to 6 μg/mL. The samples were stable after three cycles of freeze/thawing and extraction efficiency rates above 95% were obtained. In vitro skin penetration studies of an aqueous solution and a commercial cream of 5-FU were performed. The cream improved 5-FU retention into the skin and permeation through the skin compared to the solution. Therefore, the method developed herein can be applied to the study of formulations for topical delivery of 5-FU.


Effects of Roundup formulations on biochemical biomarkers and male sperm quality of the livebearing Jenynsia multidentata.
Roundup® formulations are the most consumed glyphosate-based herbicides in the world. When applied, they may reach water bodies and exert toxicity toward non-target species. This study evaluated and compared the effects of different variations of Roundup on biochemical biomarkers as oxidative parameters and Acethylchorinesterase (AChE) activity, and sperm quality of the livebearing Jenynsia multidentata. Fish were acutely (96 h) exposed to Roundup Original® (RO), Roundup Transorb® (RT) and Roundup WG® (RWG) at 0.0, 0.5, 1 and 5 mg L-1 of nominal glyphosate. The highest mortality (60%) was observed for fish exposed to RT at the highest concentration tested and at 0.5 mg L-1 non-mortality was observed, so this concentration was chosen for the experiments. Fish exposed to RO and RT (24 and 96 h) presented a state of oxidative imbalance, which caused lipid peroxidation (LPO) in their livers. Oxidative stress was more severe in RO treatment, which may be resulted in the highest hepathosomatic index at 96 h. However, fish exposed to RT presented a marked inhibition of AChE activity from membrane cells of muscle and brain tissues. Sperm quality was investigated in livebearing exposed (24 and 96 h) to the three formulations. Spermatozoa motility and concentration were affected by all formulations. Overall, Roundup formulations are harmful to the fish J. multidentata at 0.5 mg L-1 of glyphosate; however, mechanisms and potential of toxicity are different between formulations. The J. multidentata also represents a sensitive species and a good regional bio-monitor.


The Predictive Factors for Readmission and Rehospitalization After Retrograde Intrarenal Surgery: The Results of RIRSearch Study Group.
Purpose: Retrograde intrarenal surgery (RIRS) is a safe and effective treatment option for upper urinary tract stones smaller than 2 cm. Although several studies have documented perioperative and postoperative complications related to RIRS, there exists limited data regarding the readmission and rehospitalization of patients after RIRS. The aims of the study were to document the rates of readmission and rehospitalization after RIRS and to determine the predictive factors for readmission and rehospitalization. Materials and Methods: In this study, we retrospectively analyzed patients who underwent RIRS for the treatment of renal stone disease and were unexpectedly readmitted to the hospital within 30 days after discharge. The hospital admission systems were used to determine readmissions and rehospitalizations. Readmission and rehospitalization rates, causes, and treatment procedures were evaluated. Univariate and multivariate analyses of clinicodemographic properties were performed to evaluate possible predictive factors for readmission and rehospitalization after RIRS. Results: A total of 1036 patients were included in the study. Of these patients, 103 (9.9%) were readmitted to the hospital. Among these readmissions, 35 patients (33.9%) were rehospitalized and 14 (13.6%) underwent surgical intervention. The most common reasons for readmission were renal colic and fever. The presence of preoperative pyuria (odds ratio [OR] 1.86), stone volume (OR 1.54), postoperative complications (OR 3.66), and stone-free status (OR 0.46) were predictive factors for readmission, whereas hospitalization time (OR 1.32), postoperative complications (OR 9.70), and stone-free status (OR 0.06) were predictive factors for rehospitalization after RIRS. Conclusion: Nearly 10% of patients who underwent RIRS were readmitted to the hospital within the first month after discharge, and some were rehospitalized. Preoperative pyuria, high stone volume, presence of postoperative complications, and low stone-free status predicted this readmission and rehospitalization. Clinicians must recognize these predictive factors and inform their patients about this possibility.


Choosing drug use measures for treatment outcome studies. II. Timing baseline and follow-up measurement.
The use of different approaches to measurement in drug abuse treatment outcome studies has resulted in a lack of comparability across studies. This paper reviews different approaches to timing of baseline and follow-up periods and to dealing with time periods during which follow-up subjects are not "at risk" for drug use. Length and timing of baseline and follow-up periods are considered as well as periods of time within which specific drug use outcomes are measured. It is suggested that research focus on describing the natural course of drug use both prior to and following treatment, in order to determine the most appropriate length and timing of follow-up periods. It is recommended that investigators report drug use data from both "at risk" and "not at risk" periods, and that they choose methods of controlling for time "at risk" which do not eliminate important drug use data from analyses.


International standards for radiation protection.
International standards for radiation protection are issued by many bodies. These bodies differ to a large extent in their organisation, in the way the members are designated and in the way the international standards are authorised by the issuing body. Large differences also exist in the relevance of the international standards. One extreme is that the international standards are mandatory in the sense that no conflicting national standard may exist, the other extreme is that national and international standards conflict and there is no need to resolve that conflict. Between these extremes there are some standards or documents of relevance, which are not binding by any formal law or contract but are de facto binding due to the scientific reputation of the issuing body. This paper gives, for radiation protection, an overview of the main standards issuing bodies, the international standards or documents of relevance issued by them and the relevance of these documents.


Quality assessment of systematic reviews of the significance of keratinized mucosa on implant health.
The aim of this overview was to assess the methods, quality, and outcomes of systematic reviews conducted to evaluate the importance of keratinized mucosa (KM) for the maintenance of peri-implant tissue health in humans. An electronic search was conducted without date or language restriction using the MEDLINE/PubMed, Cochrane Library, Web of Science, and Embase databases up to December 2015. The eligibility criteria included systematic reviews with/without meta-analysis and with a focus on the influence of KM on peri-implant health around implants. Two independent authors performed the quality analysis of the reviews with the AMSTAR guidelines and another checklist proposed in 2003. After screening, four systematic reviews were selected. The present study demonstrated the existence of structural and methodological variability among the systematic reviews with/without meta-analysis. None of the systematic reviews that were included in the study obtained the maximum score in the two quality analyses performed. All systematic reviews included reported a positive association between an adequate KM width (≥2mm) and peri-implant health. There is still insufficient data on the long-term survival and success rates of dental implants. Prospective studies evaluating the importance of KM for the long-term maintenance of dental implants are needed.


Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats.
Methcathinone (MCAT; 1), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although S(-)MCAT is several-fold more potent than R(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (i.e., as releasing agents) and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats, S(-)MCAT was approximately twice as potent as its R-enantiomer. Achiral analogs, α-methyl MCAT (3) and α-des-methyl MCAT (4), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.


[A Rare Case of Ruptured Internal Carotid-Posterior Communicating Artery Aneurysm Associated with Contralateral Delayed Oculomotor Nerve Palsy].
A 55-year-old man presented with difficulty breathing, chest pain, and disturbance of consciousness, and was transferred to our hospital. Initial whole body CT revealed a diffuse subarachnoid hemorrhage(SAH)with severe pulmonary edema that was considered neurogenic in origin. He received controlled ventilation under sedation and conservative care for the SAH. One day after the onset of the SAH, his left pupil suddenly became dilated to 6mm, with no reaction to light. Head CT showed no new bleeding. Subsequent CT angiogram revealed a right internal carotid-posterior communicating artery aneurysm(IC-PC AN)with a posterior-lateral projection; however, no vessel abnormality was observed in the left anterior or posterior circulations. The aneurysm was successfully treated with coil embolization. We reviewed reported cases of isolated oculomotor nerve palsy(ONP), without direct compression by ruptured aneurysms, and found that only 11 cases exist, including our case. Interestingly, six of them were associated with anterior communicating artery aneurysms. A mass effect, chemical stimulation, and a jet stream of blood were proposed as the mechanisms of this rare type of ONP, in addition to the specific neurovascular relationships between the oculomotor nerve and the posterior cerebral/posterior communicating/superior cerebellar arteries, with abnormal nerve contact or compression. Though rare, ruptured IC-PC ANs could cause contralateral ONP; other types of ruptured aneurysms may also lead to indirect effects on nervous structures without direct compression. This type of rare presentation of ruptured aneurysms should be considered, especially in cases of multiple aneurysms, such as IC-PC ANs.


[Analysis of 59 Anaphylactic Death Cases].
To analyze the cases of anaphylactic death cases and explore the standards of judicial expertise of anaphylactic death for providing evidence for judicial expertise. Fifty-nine cases death due to allergic reaction in Shanghai were collected. And details of medical history, clinical manifestation of anaphylactic reaction and postmortem examination findings were reviewed for all cases. In the 59 cases, there were 58 cases died from drug allergy, including 77.6% of them were antibiotics. The rates of treating in standard hospital and illegal clinic were 37.3% and 61.0%, respectively. The allergic symptoms were dyspnea and facial cyanosis. The time from contacting allergens to death ranged from 1 min to 3 d. The concentration of total serum IgE ranged from 50 to 576.92 IU/mL. The results of clinical manifestation and pathological anatomy had obviously changes. Based on the exclusion of all other cause of death and synthetically analysis of details of cases, medical history, clinical manifestation and anatomy, the conclusion of anaphylactic death can reached. The details of cases including clinical history, exposure to allergens, and clinical manifestation play an important role in diagnosis of anaphylactic death.


Identification of rat cell lines that preferentially express insulin-like growth factor binding proteins rlGFBP-1, 2, or 3.
The bioavailability and action of the insulin-like growth factors (IGFs) are determined by specific IGF-binding proteins (IGFBP) to which they are complexed. Complementary DNA clones have been isolated that encode three related IGFBPs: human IGFBP-1 (hIGFBP-1), human IGFBP-3 (hIGFBP-3), and rat IGFBP-2 (rIGFBP-2). IGFBP-1 and IGFBP-3 are regulated differently in human plasma, suggesting that they have different functions. In order to study the molecular basis of the regulation of the different IGFBPs, we have identified a panel of rat cell lines that express a single predominant binding protein and developed an assay strategy to distinguish the different binding proteins. Proteins in conditioned medium were examined by ligand blotting, and by immunoprecipitation and immunoblotting using antibodies to rIGFBP-2 and hIGFBP-1; RNAs were hybridized to cDNA probes for rIGFBP-2 and hIGFBP-1. 1) C6 glial cells and B104 neuroblastoma cells express an approximately 40 kilodalton (kDa) glycosylated binding protein that most likely represents rIGFBP-3, the binding subunit of the 150 kDa IGF: binding protein complex in adult rat serum. The C6 and B104 binding proteins do not react with antibodies to rIGFBP-2, and RNAs from C6 and B104 cells do not hybridize to cDNA probes for rIGFBP-2 or hIGFBP-1. 2) BRL-3A, Clone 9, and TRL 12-15 cell lines derived from normal rat liver express rIGFBP-2, a 30 kDa nonglycosylated IGF-binding protein that is recognized by antibodies to rIGFBP-2 but not by antibodies to hIGFBP-1. RNAs from these cells hybridize to a rIGFBP-2 cDNA probe, but not to a hIGFBP-1 probe. 3) H35 rat hepatoma cells express a 30 kDa nonglycosylated IGFBP that is presumptively identified as rIGFBP-1. It does not react with antibodies to rIGFBP-2, but is recognized by polyclonal and monoclonal antibodies to hIGFBP-1. RNA from H35 cells hybridizes to a hIGFBP-1 cDNA probe, but not to a rIGFBP-2 probe. Expression of rIGFBP-1 by the H35 cell line has enabled us to establish and validate specific assays for this protein that allow us to study its regulation in intact rats. Identification of a panel of rat cell lines expressing specific IGFBPs should be useful in elucidating the molecular mechanisms of IGFBP regulation.


Do child-father and child-mother preschool insecure attachment types predict the development of externalizing behaviors in boys and girls during middle childhood?
Past meta-analyses show that both child-mother and child-father attachment insecurity are independently and jointly associated with more externalizing behaviors in children. Little is known, however, on the ways that different types of insecure attachment independently and jointly predict the development of externalizing behaviors over time. Existing work also neglects the impact of children's gender within the context of child-father relationships. The current study addresses these limitations by investigating how insecure type of child-father attachment, child-mother attachment, and their interaction in the preschool years predict boys' and girls' externalizing behaviors in middle childhood, when controlling for children's externalizing behaviors in the preschool years. The sample included 144 preschool-aged children (M = 46.89 months, SD = 8.77, 83 girls) and both of their parents. At Time 1, children completed independent separation-reunion procedures with each parent, which were coded using the Preschool Attachment Rating Scales. At Time 1 and Time 2 (5 years later), mothers and fathers completed the Strengths and Difficulties Questionnaire to report on their children's externalizing behaviors. Results showed no systematic differences in the way that child-mother and child-father attachment predicted the development of externalizing behaviors in boys and girls. Across all children, results identified an interaction of child-father and child-mother ambivalence, by which the presence of ambivalence toward both parents predicted the development of more externalizing behaviors. In addition, child-father controlling-caregiving attachment predicted the development of fewer externalizing behaviors. These results provide insight into the ways that insecure child-father and child-mother attachment predict later socioemotional adaptation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Practical experience of the application of ICRP models in internal dose assessment.
The introduction of the Ionising Radiations Regulations 1999 in the UK, which came into force on 1 January 2000, led to significant changes in internal dose assessment. Before this date, assessments were based on the methodology from ICRP Publication 26 and, in general, made use of simple models such as those detailed in ICRP Publication 30. However, the introduction of the new Regulations required the use of ICRP Publication 60 methodology, and, at the same time, the latest ICRP biokinetic models were introduced. Many of these newer models were considerably more complex than the ones they replaced. In particular, the use of 'recycling', where activity is constantly recirculated between different organs, meant that the models could not simply be implemented by use of the Skrable formula, as detailed in ICRP Publication 30. This paper outlines two aspects of the application of these latest ICRP models. First, the problems encountered during implementation of these models are detailed, and secondly, it covers the practical experience of using the resulting computer programs for internal dose assessment.


Characteristics of 2020 stock market crash: The COVID-19 induced extreme event.
A sudden fall of stock prices happens during a pandemic due to the panic sell-off by the investors. Such a sell-off may continue for more than a day, leading to a significant crash in the stock price or, more specifically, an extreme event (EE). In this paper, Hilbert-Huang transformation and a structural break analysis (SBA) have been applied to identify and characterize an EE in the stock market due to the COVID-19 pandemic. The Hilbert spectrum shows a maximum energy concentration at the time of an EE, and hence, it is useful to identify such an event. The EE's significant energy concentration is more than four times the standard deviation above the mean energy of the normal fluctuation of stock prices. A statistical significance test for the intrinsic mode functions is applied, and the test found that the signal is not noisy. The degree of nonstationarity test shows that the indices and stock prices are nonstationary. We identify the time of influence of the EE on the stock price by using SBA. Furthermore, we have identified the time scale ( τ) of the shock and recovery of the stock price during the EE using the intrinsic mode function obtained from the empirical mode decomposition technique. The quality stocks with V-shape recovery during the COVID-19 pandemic have definite τ of shock and recovery, whereas the stressed stocks with L-shape recovery have no definite τ. The identification of τ of shock and recovery during an EE will help investors to differentiate between quality and stressed stocks. These studies will help investors to make appropriate investment decisions.


[DDP-sensitivity-related genes in 10 lung cancer cell lines].
To search for genes related to cisplatin (DDP) sensitivity in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines. The sensitivity of 4 SCLC lines and 6 NSCLC lines to DDP was evaluated by MTT assay. The expression of 1291 genes related to DDP-sensitivity in the 10 cell lines was measured by cDNA macroarray and the relationship between genes and DDP-sensitivity was analyzed. 20 genes were negatively related to DDP-sensitivity in the SCLC and NSCLC cell lines, including Metallothionein, Cathepsin B, TIMP1, TNF-R1, TGF beta-induced 68 000, Cathepsin L, Galectin-1, Annexin 11, PAI-1, IGFBP4, UPAR, Jagged, CD13, alpha 1 A-AR, EphA2 (Eck), APC, RhoC, Fibromodulin, GATA-6 and HSC 70, while only procoagula and MDM2 were positively related to DDP-sensitivity in the SCLC and NSCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the SCLC cell lines, including VHL, MMP-7, Elongin A, GSK-3 beta, SLC, Galectin-3, integrin beta 5, moesin, IKK beta, and ETV 1, while only AT2 was positively related to DDP-sensitivity in the SCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the NSCLC cell lines, including Clusterin, FG FR-2, Thrombospondin 1, HSP 32, Lactate dehydrogenase A, P300, Thymosin beta l0, CD81, C/EBP gamma, Rak, while only CaMKK and TPA were positively related to DDP-sensitivity in the NSCLC cell lines. There were 45 genes related to DDP-sensitivity in 10 lung cancer cell lines. There were 22 co-expressed genes in both SCLC and NSCLC cell lines, and only 11 and 12 genes expressed in the SCLC and NSCLC cell lines, respectively.


Population and family planning in Bangladesh.
The family planning programme (FPP) in Bangladesh and its role in reducing the fertility rate in the country has been at the centre of much scholarly debate. The current contraceptive prevalence rate (CPR) is 61%- double the rate observed in Pakistan, while the total fertility rate is 2.3 children per woman. This paper highlights both the supply-and demand-side factors explaining trends in contraceptive use over the last four decades. It identifies the challenges plaguing the programme today that range from funding and staffing deficiencies to bottlenecks in procurement processes. The paper uses secondary data sources such as Bangladesh Demographic and Health Survey (BDHS) 2004 and 2011 to show Family Planning trends in Bangladesh and uses the Spectrum software to forecast trends for the year 2015. The central message is that the current contraceptive method mix, which is heavily biased towards temporary methods, cannot support a sustained decline in fertility. The authors' projected estimates reveal that in order to achieve replacement-level fertility by 2016, users of long-acting and permanent methods would need to be increased by 8-9 million. Drawing on global experiences, the paper outlines greater flexibility in the use of funds and a regionally-targeted approach, among other options, that could be adopted to ensure that national population targets are met.


Droplet Enhanced Fluorescence for Ultrasensitive Detection Using Inkjet.
A fluorescence enhanced phenomenon was found within a micrometer-sized liquid droplet, and it was adopted to construct droplet enhanced fluorescence (DEF) for ultrasensitive fluorescence detection. In this paper, an inkjet was utilized to eject perfect spherical droplets to construct a microspherical resonator and to develop a DEF system. It was utilized to implement ultrasensitive fluorescence detection in a liquid specimen with a volume of several microliters. The DEF detection of fluorescent molecules, fluorescein sodium, was used as a model to validate the proposed enhanced fluorescence detection method. A low limit of detection (LOD) for fluorescein sodium of 124 pM was obtained. The sensitive detection of single stranded DNA (ssDNA) was experimentally completed, with a wide range of linearity with a LOD of 312 pM. The proposed mechanism can be used as an ultrasensitive detection technique for analyzing microliters of liquid samples.


The molecular mechanism and clinical significance of LDHA in HER2-mediated progression of gastric cancer.
The use of human epidermal growth factor receptor-2 (HER2) as a biomarker for gastric cancer (GC) has greatly helped some patients receive benefit from HER2-targeted therapy. However, the correlation between HER2 and other biochemical markers is unclear. The aim of this study was to examine the relationship between HER2 and lactate dehydrogenase A (LDHA) in GC tissues and GC cells. The correlation between clinicopathological features and HER2 was analyzed in 179 cases of GC. The expression of HER2 and LDHA was examined by immunohistochemical staining in 12 pairs of GC tissues and by western blotting in seven pairs of fresh GC tissues and adjacent normal tissues. Wound healing, transwell migration assay, quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR), and LDH activity assays were performed with GC cells. HER2 expression and serum LDH levels were closely correlated (P = 0.027) in 179 GC patient cases. Immunohistochemical staining demonstrated a positive correlation between HER2 and LDHA in 12 pairs of GC tissues (P = 0.0308). Knocking down LDHA suppressed cell migration and invasion in GC cells. In addition, HER2 positively regulated hypoxia-inducible factor-1α (HIF-1α) and LDHA. Furthermore, the expressions of HER2, HIF-1α, and LDHA were consistent in 5/7 pairs of fresh GC tissues and adjacent normal tissues as well as in GC cell lines. The HER2-HIF-1α-LDHA axis may serve as the basis for new methods and strategies for the treatment of GC.


Hypoxia-responsive ERFs involved in postdeastringency softening of persimmon fruit.
Removal of astringency by endogenously formed acetaldehyde, achieved by postharvest anaerobic treatment, is of critical importance for many types of persimmon fruit. Although an anaerobic environment accelerates de-astringency, it also has the deleterious effect of promoting excessive softening, reducing shelf life and marketability. Some hypoxia-responsive ethylene response factors (ERFs) participate in anaerobic de-astringency, but their role in accelerated softening was unclear. Undesirable rapid softening induced by high CO2 (95%) was ameliorated by adding the ethylene inhibitor 1-MCP (1 μL/L), resulting in reduced astringency while maintaining firmness, suggesting that CO2 -induced softening involves ethylene signalling. Among the hypoxia-responsive genes, expression of eight involved in fruit cell wall metabolism (Dkβ-gal1/4, DkEGase1, DkPE1/2, DkPG1, DkXTH9/10) and three ethylene response factor genes (DkERF8/16/19) showed significant correlations with postdeastringency fruit softening. Dual-luciferase assay indicated that DkERF8/16/19 could trans-activate the DkXTH9 promoter and this interaction was abolished by a mutation introduced into the C-repeat/dehydration-responsive element of the DkXTH9 promoter, supporting the conclusion that these DkERFs bind directly to the DkXTH9 promoter and regulate this gene, which encodes an important cell wall metabolism enzyme. Some hypoxia-responsive ERF genes are involved in deastringency and softening, and this linkage was uncoupled by 1-MCP. Fruit of the Japanese cultivar 'Tonewase' provide a model for altered anaerobic response, as they lost astringency yet maintained firmness after CO2 treatment without 1-MCP and changes in cell wall enzymes and ERFs did not occur.


Immunopathology of RSV infection: prospects for developing vaccines without this complication.
Respiratory syncytial virus is the most important cause of lower respiratory tract infection in infants and young children. RSV clinical disease varies from rhinitis and otitis media to bronchiolitis and pneumonia. An increased incidence of asthma later in life has been associated with the more severe lower respiratory tract infections. Despite its importance as a pathogen, there is no licensed vaccine against RSV. This is due to a number of factors complicating the development of an effective and safe vaccine. The immunity to natural RSV infection is incomplete as re-infections occur in all age groups, which makes it challenging to design a protective vaccine. Second, the primary target population is the newborn infant, which has a relatively immature immune system and maternal antibodies that can interfere with vaccination. Finally, some vaccines have resulted in a predisposition for exacerbated pulmonary disease in infants, which was attributed to an imbalanced Th2-biased immune response, although the exact cause has not been elucidated. This makes it difficult to proceed with vaccine testing in infants. It is likely that an effective and safe vaccine needs to elicit a balanced immune response, including RSV-specific neutralising antibodies, CD8 T-cells, Th1/Th2 CD4 T-cells and preferably secretory IgA. Subunit vaccines formulated with appropriate adjuvants may be adequate for previously exposed individuals. However, intranasally delivered genetically engineered attenuated or vectored vaccines are currently most promising for newborns, as they are expected to induce a balanced immune response similar to that elicited to natural infection and not be subject to interference from maternal antibodies. Maternal vaccination may be the optimal strategy to protect the very young infants.


Outer Membrane Vesicles Derived from Salmonella Enteritidis Protect against the Virulent Wild-Type Strain Infection in a Mouse Model.
Foodborne contamination and salmonellosis caused by Salmonella Enteritidis (S. Enteritidis) are a significant threat to human health and poultry enterprises. Outer membrane vesicles (OMVs), which are naturally secreted by gram-negative bacteria, could be a good vaccine option because they have many biologically active substances, including lipopolysaccharides (LPS), outer membrane proteins (OMPs), and phospholipids, as well as periplasmic components. In the present study, we purified OMVs derived from S. Enteritidis and analyzed their characteristics through silver staining and sodium dodecyl sulfate polyacrylamide gel electrophoresis. In total, 108 proteins were identified in S. Enteritidis OMVs through liquid chromatography tandem mass spectrometry analysis, and OMPs, periplasmic proteins, and extracellular proteins (49.9% of total proteins) were found to be enriched in the OMVs compared with bacterial cells. Furthermore, native OMVs used in immunizations by either the intranasal route or the intraperitoneal route could elicit significant humoral and mucosal immune responses and provide strong protective efficiency against a lethal dose (~100-fold LD50) of the wild-type S. Enteritidis infection. These results indicated that S. Enteritidis OMVs might be an ideal vaccine strategy for preventing S. Enteritidis diseases.


A Diffusive Gradient-in-Thin-Film Technique for Evaluation of the Bioavailability of Cd in Soil Contaminated with Cd and Pb.
Management of heavy metal contamination requires accurate information about the distribution of bioavailable fractions, and about exchange between the solid and solution phases. In this study, we employed diffusive gradients in thin-films (DGT) and traditional chemical extraction methods (soil solution, HOAc, EDTA, CaCl₂, and NaOAc) to determine the Cd bioavailability in Cd-contaminated soil with the addition of Pb. Two typical terrestrial species (wheat, Bainong AK58; maize, Zhengdan 958) were selected as the accumulation plants. The results showed that the added Pb may enhance the efficiency of Cd phytoextraction which is indicated by the increasing concentration of Cd accumulating in the plant tissues. The DGT-measured Cd concentrations and all the selected traditional extractants measured Cd concentrations all increased with increasing concentration of the addition Pb which were similar to the change trends of the accumulated Cd concentrations in plant tissues. Moreover, the Pearson regression coefficients between the different indicators obtained Cd concentrations and plants uptake Cd concentrations were further indicated significant correlations (p < 0.01). However, the values of Pearson regression coefficients showed the merits of DGT, CaCl₂, and Csol over the other three methods. Consequently, the in situ measurement of DGT and the ex situ traditional methods could all reflect the inhibition effects between Cd and Pb. Due to the feature of dynamic measurements of DGT, it could be a robust tool to predict Cd bioavaiability in complex contaminated soil.


PPARgamma agonists sensitize PTEN-deficient resistant lung cancer cells to EGFR tyrosine kinase inhibitors by inducing autophagy.
We aimed to develop novel drug combination strategy to overcome drug resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in the treatment of non-small cell lung cancer (NSCLC). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor, which upon activation upregulates phosphatase and tensin homolog (PTEN) to inhibit cell signaling downstream of PI3K to mediate apoptosis. To this end, PTEN loss is a known mechanism contributing to resistance to EGFR TKIs. Therefore, PPARγ agonists are hypothesized to overcome EGFR TKI resistance. Using human NSCLC cell models with PTEN deficiency, the potentiation of EGFR TKI anticancer activity by PPARγ agonists was evaluated. PPARγ agonists were found to upregulate PTEN, subsequently inhibiting the PI3K-Akt signaling pathway, and thus enhancing the anticancer activity of gefitinib (a first generation EGFR TKI). Chemical and genetic inhibition of PPARγ were shown to prevent this potentiation of anticancer activity by PPARγ agonists, thus confirming the crucial role played by PPARγ activation. Interestingly, the tested PPARγ agonists were also found to induce autophagy, as evidenced by the increased expression of an autophagy marker LC3-II and the autophagic degradation of p62/SQSTM1. PPARγ agonists-induced autophagic cell death was believed to contribute to the circumvention of resistance in PTEN-deficient cells because the genetic silencing of ATG5 (an autophagy mediator) was found to eliminate the drug potentiation effect by the PPARγ agonists. Our findings thus provide the basis for the rational and personalized use of PPARγ agonists in combination with EGFR TKIs in lung cancer patients.


"When diet and exercise are not enough": an examination of lifestyle change inefficacy claims in direct-to-consumer advertising.
Previous research suggests that direct-to-consumer (DTC) advertisements for pharmaceutical drugs have the potential to influence consumers' perceptions of whether symptoms should be treated medically and/or through behavior change. However, the relative frequency of messages emphasizing these approaches in pharmaceutical advertising remains largely unknown. A content analysis of print and television advertisements for cholesterol management medication between 1994 and 2005 (for print) and between 1999 and 2007 (for television) was conducted. First, the extent to which established theoretical constructs drawn from health communication scholarship are depicted in the content of DTC cholesterol advertisements is quantified. Second, specific claims about behavior change inefficacy when a pharmaceutical alternative is available are identified. Findings indicate that DTC ads offer many mixed messages about the efficacy of diet and exercise in reducing cholesterol and risk of heart disease. Theoretical and practical implications of this work are discussed.


Brain metastasis in patients with uterine cervical cancer.
The purpose of this study was to describe the features of patients with brain metastasis from cervical cancer. The medical records of patients with cervical cancer between February 2001 and June 2011 were reviewed retrospectively. Clinical characteristics, symptoms, treatment and survival in patients with brain metastasis were analyzed. Eleven patients with brain metastasis from cervical cancer were identified, representing an incidence of brain metastasis in the study population of 0.45%. Median patient age at initial diagnosis of cervical cancer was 50 years (range 33-75 years). Non-squamous cell carcinoma was diagnosed in six (54.5%) of the 11 patients, with small cell carcinoma diagnosed in two patients. Ten of the 11 patients had lung-related metastasis at presentation; eight patients had lung metastasis, one had mediastinal lymph node metastasis, and one had pleural metastasis. The median interval from diagnosis of cervical cancer to identification of brain metastasis was 15.4 months (range 3.4-83.3 months). Nine patients presented with neurologic symptoms, such as headache, nausea, vomiting, seizure and extremity weakness. Initially, six patients received whole brain radiotherapy: three patients received chemotherapy; one underwent surgery; and one patient refused treatment. The median survival time after diagnosis of the brain metastases was 5.9 months (range 0.7-19 months). The prognosis after diagnosis of the brain metastasis in patients with uterine cervical cancer is poor. The small cell type and lung metastasis seem to be related with brain metastasis and may be regarded as risk factors.


Fatal Aspergillus myocarditis following short-term corticosteroid therapy for chronic obstructive pulmonary disease.
A 58-y-old man with chronic obstructive pulmonary disease (COPD) was admitted for treatment of an acute exacerbation of his illness. The patient's condition initially improved after therapy with oxygen, bronchodilators, antibiotic and methylprednisolone (40 mg every 8 h) was started. Soon afterwards, however, the patient's clinical status deteriorated and he died on the fifth hospital day. Post-mortem examination revealed unsuspected, isolated fungal myocarditis. The fungus was later identified as Aspergillus by indirect immunofluorescence. To our knowledge, this is the first case of fatal Aspergillus myocarditis related to short-term (< 1 week) steroid therapy in a COPD patient. We believe that this case provides further evidence to support the possibility of life-threatening infections in COPD patients who receive even a short course of corticosteroid treatment.


Non-invasive treatment of pyogenic granuloma by using Nd:YAG laser.
Pyogenic granuloma is a 'reactive lesion' in the oral cavity caused due to hormonal imbalance or poor oral hygiene. There are different methods to excise this lesion but most successful is treatment with lasers. Currently, there are different lasers available commercially and are used by clinicians to excise this lesion. In this case report, a 20-year-old female patient reported to the department with a complaint of overgrowth of gingiva on lower canine. It was excised by using neodymium-doped yttrium aluminium garnet laser and the patient was asked for regular follow-up after 1 week and 6 months. The excised lesion was sent to pathology where the lesion was confirmed to be pyogenic granuloma. The patient reported no pain, no blood loss during or postsurgery. Laser is a useful technique for excisional surgeries; it is safe, effective and reduces time of treatment as well as time of healing.


Congenital Long QT Syndrome: An Update and Present Perspective in Saudi Arabia.
Primary cardiac arrhythmias are often caused by defects, predominantly in the genes responsible for generation of cardiac electrical potential, i.e., cardiac rhythm generation. Due to the variability in underlying genetic defects, type, and location of the mutations and putative modifiers, clinical phenotypes could be moderate to severe, even absent in many individuals. Clinical presentation and severity could be quite variable, syncope, or sudden cardiac death could also be the first and the only manifestation in a patient who had previously no symptoms at all. Despite usual familial occurrence of such cardiac arrhythmias, disease causal genetic defects could also be de novo in significant number of patients. Long QT syndrome (LQTS) is the most eloquently investigated primary cardiac rhythm disorder. A genetic defect can be identified in ∼70% of definitive LQTS patients, followed by Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Brugada syndrome (BrS), where a genetic defect is found in <40% cases. In addition to these widely investigated hereditary arrhythmia syndromes, there remain many other relatively less common arrhythmia syndromes, where researchers also have unraveled the genetic etiology, e.g., short QT syndrome (SQTS), sick sinus syndrome (SSS), cardiac conduction defect (CCD), idiopathic ventricular fibrillation (IVF), early repolarization syndrome (ERS). There exist also various other ill-defined primary cardiac rhythm disorders with strong genetic and familial predisposition. In the present review we will focus on the genetic basis of LQTS and its clinical management. We will also discuss the presently available genetic insight in this context from Saudi Arabia.


Intercalation of nanostructured CeO2 in MgAl2O4 spinel illustrates the critical interaction between metal oxides and oxides.
Heterogeneous catalytic oxidation arises from the prerequisite oxygen activation and transfer ability of metal oxide catalysts. Thus, engineering intercalated nanounits and heterophase metal oxide structures, and forming interstitial catalyst supports at the nanoscale level can drastically alter the catalytic performances of metal oxides. This is particularly important for ceria-based nanomaterial catalysts, where the interactions of reducible ceria (CeO2) and nonreducible oxides are fundamental for the preparation of enhanced catalysts for oxygen-involved reactions. Herein, we intercalated nanostructured CeO2 in the bulk phase of magnesium aluminate spinel (MgAl2O4, referred to as MgAl), produced the interstitial effect between CeO2 nanoparticles and MgAl crystallites, thus boosting their oxygen transfer and activation capability. This nanoscaled intercalation engineering significantly enhanced the number and quality of tight contact points between the nanostructured CeO2 and MgAl units. Therefore, the oxygen storage/release capability (OSC) is exceptionally improved as revealed by various characterizations and catalytic carbon oxidation reaction. A mechanism similar to the Mars-van Krevelen process at the nanoscale level was invoked to explain the catalytic oxidation mechanisms. The reactive oxygen species of gaseous O2 originate formed the bulk of the as-obtained nanomaterial, where strong interactions between the CeO2 and MgAl components occured, which were subsequently released and diffused to the catalyst-interface at elevated temperatures. Silver supported on Ce-MgAl produced an approximately 4-fold higher concentration of active oxygen species than Ag/MgAl, and gives the optimum low-temperature oxidation at 229 °C. This study verifies the importance of the redox performance of ceria-spinel with enhanced OSC, which validates that the arrangement of contacts at the nanoscale can substantially boost the catalytic reactivity without varying the microscale structure and properties of spinel.


Elderly Canadians residing in long-term care hospitals: Part I. Medical and dental status.
Oral diseases and conditions have been identified as a significant problem for elderly residents of long-term care (LTC) hospitals in developed countries, yet little recent information is available for the Canadian population. To describe the medical, dietary, oral microbial, oral hygiene and dental status of elderly Canadians living in LTC hospitals in Vancouver and surrounding communities. A sample of 369 elderly dentate hospital residents (mean age 83.9 years, 281 women [76.2%]) were examined, and their medical status and medications, oral status and type of hospital were documented. Oral hygiene practices and diet (specifically intake of refined carbohydrates) were evaluated. Subjects with xerostomia and subjects taking medications with hyposalivary side effects were identified, and salivary Streptococcus mutans and Lactobacillus were cultured. The mean plaque index was 1.3; men had a higher plaque index than women and residents of extended care hospitals had a higher plaque index than those in intermediate care hospitals. The mean bacterial score per millilitre of saliva was 9.7 105 colony-forming units (CFU) for Streptococcus mutans and 1.6 105 CFU for Lactobacillus. On average, each subject had 6.3 sound teeth, and 9.3 teeth had been restored. Although almost half of the subjects had visited a dental office in their community within the past 5 years, the elderly hospital residents in this study had few remaining teeth and suffered from poor oral hygiene. Prevention strategies (such as diet, oral hygiene and antimicrobial agents) rather than dental interventions (such as restorations and extractions) alone may be needed to control oral diseases in this susceptible population.


Expression, purification and preliminary crystallographic analysis of the cryptic polo-box domain of Caenorhabditis elegans ZYG-1.
ZYG-1 is a polo-like kinase essential for centriole assembly in Caenorhabditis elegans. The targeting of ZYG-1 to nascent centrioles is via its central cryptic polo-box (CPB) domain. To shed light on the molecular basis of ZYG-1 recruitment, it is necessary to obtain structural knowledge of the ZYG-1 CPB. Here, the expression, purification and preliminary crystallographic analysis of the ZYG-1 CPB are reported. The protein was overexpressed in Escherichia coli strain BL21 (DE3), purified by multi-step chromatography and crystallized using the vapour-diffusion method. Crystals of the wild-type protein exhibited an order-disorder pathology, which was solved by reductive lysine methylation. A complete anomalous data set was collected to 2.54 Å resolution at the Se K edge (λ = 0.9792 Å). The crystal belonged to space group P2, with unit-cell parameters a = 53.3, b = 60.09, c = 87.51 Å, β = 93.31°. There were two molecules in the asymmetric unit.


Surface Oxygen Species in Metal Oxide Photoanodes for Solar Energy Conversion.
Converting and storing solar energy directly as chemical energy through photoelectrochemical devices are promising strategies to replace fossil fuels. Metal oxides are commonly used as photoanode materials, but they still encounter challenges such as limited light absorption, inefficient charge separation, sluggish surface reactions, and insufficient stability. The regulation of surface oxygen species on metal oxide photoanodes has emerged as a critical strategy to modulate molecular and charge dynamics at the reaction interface. However, the precise role of surface oxygen species in metal oxide photoanodes remains ambiguous. The review focuses on elucidating the formation and regulation mechanisms of various surface oxygen species in metal oxides, their advantages and disadvantages in photoelectrochemical reactions, and the characterization methods employed to investigate them. Additionally, the article discusses emerging opportunities and potential hurdles in the regulation of surface oxygen species. By shedding light on the significance of surface oxygen species, this review aims to advance our understanding of their impact on metal oxide photoanodes, paving the way for the design of more efficient and stable photoelectrochemical devices.


[Factors impeding obstructed teeth in their eruption. Case report].
With preparation of six study cases the objective of the authors was to abrow colleagues' attention to the fact that teeth remained in impactio and retention might cause complaints not only due to normal anatomical reasons but some complications might occur resulting from anomaly of development. The authors consider the topic extremely important by reason of the case's varieties and the clinical observations made recently and frequently. An increased attention to this case is reasonable since eruption of teeth might happen in case of removal of obstructic fact in time, permanent row of teeth returns to normal, and adequate dental arch might develop. It is also obvious that medical treatment of impact abnormalities derived from anomaly has lack of exact therapy theories, only general protocol can be provided.


Regional Diffusion of Divorce in Turkey.
While demographic change has been well documented for many Western countries, much less is known about demographic transitions in other countries, including Turkey. Demographic change in European societies can be characterized by, amongst others, increased prevalence of divorce. Although it is often argued that life courses in Turkey follow a more traditional path, little is known on determinants and patterns of divorce, despite the major socioeconomic changes Turkey has undergone over the past decades. We study the levels of divorce of women in Turkey from 1973 to 2008 to explain patterns of divorce, looking at the role of individual characteristics and the regional context. We use the Demographic Health Surveys (2003/2008), complemented with regional data on divorce, urbanization, and GDP per capita. Applying a multilevel approach, distinguishing 12 regions, we hypothesize that regions where divorce is already more prevalent, more urbanized regions, and wealthier regions in terms of GDP per capita will increase the probability of divorce. Our analyses show that levels of divorce increased over the past decades but huge regional variation remains. Sociocultural and socioeconomic factors explain this trend, and in particular urbanization and GDP per capita are key determinants for divorce.


Copper-Catalyzed Synthesis of Tetrasubstituted Enynylboronates via Chemo-, Regio-, and Stereoselective Borylalkynylation.
An efficient, catalytic method for accessing tetrasubstituted enynylboronates has been established via copper-catalyzed chemo-, regio-, and stereoselective borylalkynylation of internal alkynes. In this protocol, a range of symmetrical and unsymmetrical internal alkynes with aryl, heteroaryl, and alkyl substituents afforded fully substituted enynylboron compounds in good yields and with high levels of regio- and stereoselectivity, up to a ratio of >20:1. The enynylboron products could be further utilized in transforming the C-B bond into C-C bonds by coupling reactions.