[Multi-infarct dementia clinically simulating dementia of Alzheimer type. A comparison with angular gyrus syndrome].
A 74-year-old right-handed man with multiple cerebral infarction who presented with dementia simulating dementia of Alzheimer type (DAT) is reported. He had been well until April 20, 1987 when he developed transient right hand palsy lasting overnight. Eleven days later, he became confused, disorientated, and amnestic. He was admitted to this hospital on June 8. Physical examination revealed hypertension (170/90mmHg). On neurological examination, his consciousness was clear but he was demented. He showed disorientation, amnesia, and urinary incontinence. His most prominent symptom was disturbance of speech, including fluent aphasia and alexia with agraphia. Additionally, he showed ideomotor apraxia, construction apraxia, right-left agnosia, finger agnosia, and acalculia. On July 9, he had a transient attack of right hemiplegia with confusion. The brain CT scan performed on admission was unremarkable except for cavum septi pellucidum and a small low density area in the right basal ganglia. However, single photon emission computed tomography (SPECT) by 123I-labeled N-isopropyl-p-iodoamphetamine disclosed hypoperfusion of the cerebral blood flow in the border zones of the temporoparietal and frontal lobes on the left. A follow-up brain CT scan taken one month later demonstrated low density in the new areas corresponding to hypoperfusion shown by SPECT. Although the clinical features of the present case resembled those of DAT, dementia in this case was regarded as the result of multiple cerebral infarction since it occurred acutely with mild motor deficits, and brain CT scans and SPECT showed lesions indicating focal cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Discovering Health Benefits of Phytochemicals with Integrated Analysis of the Molecular Network, Chemical Properties and Ethnopharmacological Evidence.
Identifying the health benefits of phytochemicals is an essential step in drug and functional food development. While many in vitro screening methods have been developed to identify the health effects of phytochemicals, there is still room for improvement because of high cost and low productivity. Therefore, researchers have alternatively proposed in silico methods, primarily based on three types of approaches; utilizing molecular, chemical or ethnopharmacological information. Although each approach has its own strength in analyzing the characteristics of phytochemicals, previous studies have not considered them all together. Here, we apply an integrated in silico analysis to identify the potential health benefits of phytochemicals based on molecular analysis and chemical properties as well as ethnopharmacological evidence. From the molecular analysis, we found an average of 415.6 health effects for 591 phytochemicals. We further investigated ethnopharmacological evidence of phytochemicals and found that on average 129.1 (31%) of the predicted health effects had ethnopharmacological evidence. Lastly, we investigated chemical properties to confirm whether they are orally bio-available, drug available or effective on certain tissues. The evaluation results indicate that the health effects can be predicted more accurately by cooperatively considering the molecular analysis, chemical properties and ethnopharmacological evidence.


[Mastocytosis: advances in molecular diagnosis and therapeutics].
Systemic mastocytosis is a rare myeloproliferative-like disease, characterized by an abnormal proliferation of mast cells in various organs. Two types of clinical manifestations can be distinguished: those related to release of mast cell mediators release and those related to tumor proliferation involving different organs, these later defining systemic mastocytosis. Until recently, treatment was mainly symptomatic, without anti tumor effect. These last years, advances have been made in the understanding of the disease with the discovery of the presence, in a number of patients, of mutations of the c-kit oncogene, coding for the receptor of the major growth factor for mast cells. These mutations induce autophosphorylation of the c-kit receptor in the absence of its ligand, the Stem Cell Factor. Based on experiences acquired in the treatment of myeloproliferative disorders, evaluation of new therapeutics, such as cladribine or interferon-alpha, is in progress. Finally, it would be possible to design, in the very next future, new tyrosine kinase inhibitors targeting specifically the mutant forms of c-Kit found in patients suffering from systemic mastocytosis.


[Christopher Columbus, rubber, and rubber nipples].
The author quickly traces the history of rubber, making note of the pharmacists who therein played a role. He exhibits the history of rubber nipples and that of infant bottles, of which one of the most widely used was the "Robert Bottle."


Bovine Serum Albumin as a Versatile Platform for Cancer Imaging and Therapy.
Due to the good biocompatibility, biodegradability, facile surface functionalization and high water solubility, Bovine serum albumin has gain increasing attention in the nanomedicine. Despite there are many reviews on albumin based nanoparticles, most of them focus on one aspect of the albumin functionality, e.g., drug delivery, cancer theranostics or half-life extension in vivo. This review aims to comprehensively summary bovine serum albumin as a versatile platform in the applications of cancer imaging and therapy. We review the extensive applications of bovine serum albumin in drug carrier, surface engineering and biomimetic synthesis for cancer imaging and therapy. Based on the studies reviewed, variety of in vitro and in vivo studies show good performance of bovine serum albumin as the drug carrier, surface modification agent and biomimetic template in cancer imaging and therapy. Nevertheless, there are still some issues to be solved, e.g., the technological parameters for enhancing the drug loading efficiency and controlling drug release, optimizing surface modification process to provide more stable nanoagents, investigation of the biomimetic mechanism, in-depth study of their toxicity, further exploring their bioapplications, etc.


Correlation energy functionals dependent on an effective number of electrons: charged species and equilibrium geometries.
Recently proposed spin-dependent and spin-independent correlation energy functionals [Perez-Jimenez et al., J. Chem. Phys. 116, 10571 (2002)] based on an effective number of electrons N are extended to deal with charged systems. By introducing the concept of an effective atomic number Z analogous to N, the spin-dependent functional in combination with Becke's exchange [Becke, Phys. Rev. A 38, 3098 (1988)] yields a mean absolute error (MAE) of 5.4 kcal/mol for the 88 ionization potentials and 58 electron affinities included in the extended G2 set, and a MAE of 4.1 kcal/mol for the 312 data comprising the above plus the 148 enthalpies of formation of the extended G2 set and the 18 total energies of the neutral atoms H through Ar. Geometry optimizations performed on the 53 molecules of the G2-1 test set with the above combination of exchange and correlation functionals yield MAEs of 0.017 A and 1.5 degrees for the 68 bond lengths and 29 angles analyzed as compared with the experimental estimates.


Criticality and turbulence in a resistive magnetohydrodynamic current sheet.
Scaling properties of a two-dimensional (2d) plasma physical current-sheet simulation model involving a full set of magnetohydrodynamic (MHD) equations with current-dependent resistivity are investigated. The current sheet supports a spatial magnetic field reversal that is forced through loading of magnetic flux containing plasma at boundaries of the simulation domain. A balance is reached between loading and annihilation of the magnetic flux through reconnection at the current sheet; the transport of magnetic flux from boundaries to current sheet is realized in the form of spatiotemporal avalanches exhibiting power-law statistics of lifetimes and sizes. We identify this dynamics as self-organized criticality (SOC) by verifying an extended set of scaling laws related to both global and local properties of the current sheet (critical susceptibility, finite-size scaling of probability distributions, geometric exponents). The critical exponents obtained from this analysis suggest that the model operates in a slowly driven SOC state similar to the mean-field state of the directed stochastic sandpile model. We also investigate multiscale correlations in the velocity field and find them numerically indistinguishable from certain intermittent turbulence (IT) theories. The results provide clues on physical conditions for SOC behavior in a broad class of plasma systems with propagating instabilities, and suggest that SOC and IT may coexist in driven current sheets which occur ubiquitously in astrophysical and space plasmas.


Circuitry and role of substance P-immunoreactive neurons in the primate retina.
In this paper, we extend our previous light microscopic (LM) study of substance P (SP)-containing amacrine and ganglion cell types of the human retina (Cuenca et al. [1995] J. Comp. Neurol. 356:491-504) to an electron microscopic (EM) and confocal-imaging study in order to reveal synaptic circuitry and putative input and output neurons. SP-immunoreactive (-IR) amacrine cells in primate retina are typically wide-field cells with large cell bodies occurring in normal or displaced positions relative to the inner plexiform layer (IPL). Their main dendrites bear many spines and are monostratified in stratum 3 (S3) of the IPL. Axon-like processes arise from dendrites close to the cell body and run for hundreds of microns at the same level as the dendrites, thus forming a relatively dense plexus in S3 of the IPL. SP-IR axon processes also climb to S1 to surround some amacrine cell bodies, and others pass into the outer plexiform layer (OPL). Still other axons run down to the ganglion cell layer, where they encircle SP-IR ganglion cells and pass on to end in the nerve fiber layer. The SP-IR ganglion cell types have large cell bodies (20-22 microm diameter) and dendrites that costratify in S3 among the SP-IR amacrine cell processes. Double immunostaining and study by confocal microscopy reveals that SP-IR amacrine cells in the monkey colocalize gamma-aminobutyric acid (GABA). Their main plexus of dendrites in S3 of the IPL is skirted on the S2/S3 border by cone bipolar axons that stain for calbindin but intermingles primarily with glycinergic bipolar cell types of S3 and S3-S4. Strongly GABA-IR/weakly glycine-IR amacrine cell bodies, in addition to the SP-IR large-bodied ganglion cell type, are targets of encircling SP-IR axon processes. EM study of the human SP-IR amacrine cell indicates that input synapses to its dendrites are from bipolar cell axons of the S2/S3 border, S3, and the S3/S4 border of the IPL neuropil (33% of the synaptic input) and from amacrine cell processes (67% of the synaptic input). The input amacrine cells are of at least two distinct types based on cytological criteria. Synaptic output from the SP-IR amacrine cell dendrites is to bipolar cell axons as reciprocal synapses (31%), to amacrine cells (40%), and to ganglion cell profiles, primarily in S3 (29%) of the IPL. The SP-IR axons synapse upon SP-IR ganglion cell bodies and axons, upon normally placed and displaced amacrine cell bodies, and upon bipolar cell dendrites in the OPL. In addition, they appear to synapse among themselves. We shall discuss a wiring diagram and the possible role of SP-IR amacrine cells in the primate retina.


Hochuekkito (TJ-41), a Kampo Formula, Ameliorates Cachexia Induced by Colon 26 Adenocarcinoma in Mice.
Cachexia, a major cause of cancer-related death, is characterized by depletion of muscle and fat tissues, anorexia, asthenia, and hypoglycemia. Recent studies indicate that secretions of proinflammatory cytokines such as interleukin-6 (IL-6) play a crucial role in cachexia development, and that these cytokines are secreted from not only cancer cells but also host cells such as macrophages. In this study, we investigated the therapeutic effects of hochuekkito, a Kampo formula, on cachexia induced by colon 26 adenocarcinoma in mice. Hochuekkito treatment did not inhibit tumor growth, but significantly attenuated the reduction in carcass weight, food and water intake, weight of the gastrocnemius muscle and fat tissue around the testes, and decrease of serum triglyceride level compared with controls. Furthermore, hochuekkito treatment significantly reduced serum IL-6 level and IL-6 expression level in macrophages in tissues surrounding the tumor. In vitro studies showed that hochuekkito suppressed the production of IL-6 by THP-1 or RAW264.7 macrophage cells, although it did not affect IL-6 production by colon 26 carcinoma cells. These results suggest that hochuekkito inhibits the production of proinflammatory cytokines, particularly IL-6, by host cells such as macrophages. Therefore, hochuekkito may be a promising anticachectic agent for the treatment of patients with cancer.


Intentions to Prevent Weight Gain in Older and Younger Adults; The Importance of Perceived Health and Appearance Consequences.
This study investigates whether health and appearance consequences predict intentions to prevent weight gain and whether these relationships differ in younger versus older adults and in men versus women. UK adults aged 18-26 years (younger adults; n = 584) or >45 years (older adults; n = 107) participated in an online survey. Logistic regression assessed associations between intentions to avoid gaining weight and age, gender as well as perceived negative consequences of weight gain for health and appearance. Co-variates were ethnicity, education, weight perception and perceived weight gain vulnerability. Interactions between age, gender and perceived health and appearance consequences of weight gain were also tested. Perceived negative appearance consequences of weight gain predicted weight gain prevention intentions (OR = 9.3, p < 0.001). Health concerns were not a significant predictor of intentions overall but were a strong predictor for older adults (age × health concern interaction: OR = 13.6, p > 0.01). Concerns about feeling unattractive predict intentions to prevent weight gain. However, health consequences of weight gain are only important motivators for older adults. Future research should identify ways to shift the focus of young people from appearance concerns towards the health benefits of maintaining a healthy weight.


Effectiveness of tissue engineered three-dimensional bioactive graft on bone healing and regeneration: an in vivo study with significant clinical value.
Several strategies have been used to promote bone repair, with many failing due to the lack of osteoinduction. This report describes an approach for promoting bone healing that attempts to overcome prior shortcomings. First, the role was compared of different concentrations of gelatine (Gel), nanostructured-hydroxyapatite (nHA), simvastatin (Sim) and nHA-Sim particles on healing of small femoral bone defects in rabbits. The effective concentration of each was studied, and then a three-dimensional porous scaffold was designed using Gel, nHA and Sim, which was then cross-linked with genipin. Morphology, degradation profile and Sim delivery properties of the scaffolds were evaluated in vitro. Then, the scaffolds were subcutaneously tested in vivo to determine their biocompatibility, biodegradability and osteogenic properties. Finally, the scaffolds were implanted in a large radial bone defect model in rabbits and their effect on bone regeneration was investigated. The Gel, nHA and Sim with concentrations of 1, 1 and 5 mg/femoral hole were effective during bone healing respectively, and the Sim showed the most osteoinduction and osteoconduction when compared to controls. The Gel-Sim and Gel-nHA-Sim scaffolds continuously and homogenously released Sim into the simulated body fluid in vitro. Subcutaneously, the scaffolds were biocompatible, biodegradable and able to produce ectopic bone after 30 days. Thirty and 60 days after implantation of the scaffolds in radial bone defects, they were completely degraded and replaced with the new bone that had significantly superior morphology, mineral density, bioelectrical, biophysical and micromechanical properties compared with controls. Such bioactive grafts may be a suitable option for bone reconstruction, healing and repair.


Prehospital Predictors of Initial Shockable Rhythm in Out-of-Hospital Cardiac Arrest: Findings From the Taichung Sudden Unexpected Death Registry (THUNDER).
To identify the incidence and prehospital predictors of ventricular tachycardia/ventricular fibrillation (VT/VF) as the initial arrhythmia in patients with out-of-hospital cardiac arrest (OHCA) in central Taiwan. The Taichung Sudden Unexpected Death Registry program encompasses the Taichung metropolitan area in central Taiwan, with a population of 2.7 million and 17 destination hospitals for patients with OHCA. We performed a detailed analysis of demographic characteristics, circumstances of cardiac arrest, and emergency medical service records using the Utstein Style. From May 1, 2013, through April 30, 2014, resuscitation was attempted in 2013 individuals with OHCA, of which 384 were excluded due to trauma and noncardiac etiologies. Of the 1629 patients with presumed cardiogenic OHCA, 7.9% (n=129) had initial shockable rhythm; this proportion increased to 18.8% (61 of 325) in the witnessed arrest subgroup. Male sex (odds ratio [OR], 2.45; 95% CI, 1.46-4.12; P<.001), age younger than 65 years (OR, 2.39, 95% CI, 1.58-3.62; P<.001), public location of arrest (OR, 4.61; 95% CI, 2.86-7.44; P<.001), and witnessed status (OR, 3.98; 95% CI, 2.62-6.05; P<.001) were independent predictors of VT/VF rhythm. The proportion of patients with OHCA presenting with VT/VF was generally low in this East Asian population. Of the prehospital factors associated with VT/VF, public location of OHCA was the strongest predictor of VT/VF in this population, which may affect planning and deployment of emergency medical services in central Taiwan.


α2-containing γ-aminobutyric acid type A receptors promote stress resiliency in male mice.
Brain α2-containing GABAA receptors play a critical role in the modulation of anxiety- and fear-like behavior. However, it is unknown whether these receptors also play a role in modulating resilience to chronic stress, and in which brain areas and cell types such an effect would be mediated. We evaluated the role of α2-containing GABAA receptors following chronic social defeat stress using male mice deficient in the α2 subunit globally or conditionally in dopamine D1- or D2-receptor-expressing neurons, e.g., within the nucleus accumbens (NAc). In addition, we examined the effect of the lack of the α2 subunit on intermediates of the glutathione synthesis pathway. We found that α2-containing GABAA receptors on D2-receptor-positive but not on D1-receptor-positive neurons promote resiliency to chronic social defeat stress, as reflected in social interaction tests. The pro-resiliency effects of α2-containing GABAA receptors on D2-receptor-positive neurons do not appear to be directly related to alterations in anxiety-like behavior, as reflected in the elevated plus-maze, light-dark box, and novel open field tests. Increases in indices of oxidative stress-reflected by increases in cystathionine levels and reductions in GSH/GSSG ratios-were found in the NAc and prefrontal cortex but not in the hippocampus of mice lacking α2-containing GABAA receptors. We conclude that α2-containing GABAA receptors within specific brain areas and cell populations promote stress resiliency independently of direct effects on anxiety-like behaviors. A potential mechanism contributing to this increased resiliency is the protection that α2-containing GABAA receptors provide against oxidative stress in NAc and the prefrontal cortex.


Retarding effect of dietary restriction on the accumulation of 8-hydroxy-2'-deoxyguanosine in organs of Fischer 344 rats during aging.
An age-related accumulation in rats of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and the effect of dietary restriction on the accumulation of 8-OHdG were examined. The 8-OHdG concentrations of nuclear DNA in organs of ad libitum fed rats were similar in young and middle age, but increased significantly in kidney at 24 months of age, in heart and liver at 27 months of age, and in brain at 30 months of age. The 8-OHdG concentration in dietary-restricted rats showed no changes in any organ up to 30 months of age and then was increased at 33 months of age. Dietary restriction retarded the onset of the age-related increase in 8-OHdG concentration, although it did not reduce the concentration in young and middle age. These results suggest that the effect of dietary restriction on the extension of life-span in rats might be related to a reduction in oxidative damage.


Effects of dietary proteins and trypsin inhibitor on growth and lipid metabolism in hamsters.
The purpose of this study was to determine trypsin inhibitor (TI) activity in sweetpotato and soy flour diets and their effects on the growth and lipid metabolism of hamsters. Male Golden Syrian hamsters were fed different types of dietary protein containing casein, soyprotein, transgenic sweetpotato plus soy flour (TSPF+SF), nontransgenic sweetpotato (NTSPF) plus soy flour (NTSPF+SF), transgenic sweetpotato (TSPF) and nontransgenic sweetpotato flour for 28 days. The TI activity was highest in TSPF+SF (19.30 TIU/mg) and NTSPF+SF (17.20 TIU/mg) diets that induced growth retardation in animals, lowest in TSPF (5.80 TIU/mg) and NTSPF (5.50 TIU/mg) diets, which did not affect the growth of the animals, and negligible in casein (<1.00 TIU/mg) and soyprotein (2.00 TIU/mg) diets. Plasma total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) concentrations were significantly higher in hamsters fed the casein diet compared to those fed the soy protein, TSPF+SF, NTSPF+SF, TSPF and NTSPF diets. A positive correlation was observed between plasma TC concentrations of hamsters and dietary methionine, lysine, leucine content and methionine/glycine ratios. Liver TC and TG concentrations of hamsters fed casein were significantly higher than those of all other diet groups. The supplementation of sweetpotato flour with soy flour increased both protein and TI activity in the diets and the lipid metabolism of hamsters were unaffected by TI activity.


Glomerular dysfunction in diabetic nephropathy.
In the early stages of insulin-dependent diabetes mellitus (IDDM) in humans and in animals the renal plasma flow (RPF) and the glomerular filtration rate (GFR) have often been found higher than normal. Moreover, in a subset of IDDM patients, early abnormalities in protein excretion, termed 'subclinical proteinuria' or 'microalbuminuria' have been found. This finding is thought to be a predictor of clinically overt diabetic nephropathy. Hence, it has been proposed that high glomerular hydraulic pressure and/or plasma flow rate may be responsible for causing both proteinuria and the progression of diabetic nephropathy. However, other abnormalities such as the impaired synthesis of prostaglandins, an abnormal production of cationic polyamino-acids found in IDDM, may cause both proteinuria and nephropathy. So the role of increased glomerular pressure in initiating diabetic nephropathy is being debated. To verify whether increased GFR and proteinuria are causally linked, we have randomly allocated 12 IDDM patients (age range 25-58, mean 35 years; six males, six females) with increased GFR (131-165 ml/min, mean 145 ml/min), microalbuminuria above the normal range (range 35-130 micrograms/min, mean 80 micrograms/min) and moderate hypertension (mean blood pressure above 110 mmHg) to take a low protein diet with their standard antihypertensive therapy or their usual diet together with captopril administration (25-50 mg/day) for 4 weeks each. After low protein diet we found a significant decrease in GFR (P less than 0.05) and also in albuminuria (P less than 0.01). After captopril administration we found a small, statistically insignificant decrease in GFR with a moderate increase in filtration fraction and a significant decrease in albuminuria (P = 0.05). No correlation was found between the GFR and albuminuria variations during the low protein diet or during captopril administration. In conclusion, both the low protein diet and the captopril administration significantly decrease protein excretion. However, our data suggest that the proteinuria decrease does not correlate with the decrease in GFR, so other mechanisms besides hyperfiltration seem to be involved in the proteinuria of IDDM patients.


Clinical study of apatinib in the treatment of stage IV osteogenic sarcoma after failure of chemotherapy.
Objective: To analyze the efficacy and safety of apatinib in the treatment of stage IV osteogenic sarcoma after chemotherapy failure through a single-arm, prospective, and open clinical phase II study. Methods: Information on 34 patients with stage IV osteogenic sarcoma treated with apatinib after failure of chemotherapy in Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2019 was collected and analyzed. The participants included 23 males and 11 females, with an average age of 35.24 years (11-73 years). The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), PFS rate (PFR), and overall survival (OS) were evaluated. The treatment-related adverse events (AEs) and safety of apatinib were also evaluated. Results: Of the 34 patients, 33 were able to be evaluated for efficacy. One patient received apatinib treatment for less than one cycle; therefore, only safety analysis was performed. The 12-week clinical evaluation showed that 2 patients had a partial response (PR), 24 patients had stable disease (SD), and 7 patients had progressive disease (PD). The ORR, DCR, and PFR at 12 weeks were 6.06% (2/33), 78.79% (26/33), and 82%, respectively. By the end of the follow-up, 6 patients had SD (18.18%, 6/33), 27 patients had PD (81.82%, 27/33), and 15 patients died because of disease progression (45.45%, 15/33). The ORR was 0 (0/33), the DCR was 18.18% (6/33), and the median PFS (mPFS) was 7.89 months (95% CI: 4.56-11.21). The median OS (mOS) was 17.61 months (95% CI: 10.85-24.37). The most common treatment-related AEs were hand-foot syndrome (35.29%, 12/34), proteinuria (32.35%, 11/34), and hypertension (32.35%, 11/34). Conclusions: Apatinib is effective and well tolerated in stage IV osteogenic sarcoma patients after chemotherapy failure.


[Sleep-apnea syndrome. Elucidation, therapy and course].
Of 22 patients investigated for sleep disorders, habitual snoring and/or daytime hypersomnolence, 12(10 men) had obstructive sleep apnea syndrome (OSAS). 3 OSAS were mild, 5 moderate and 4 severe. The leading symptoms were daytime hypersomnolence and habitual snoring. As risk factors we found retro-micrognathia in 2 patients, macroglossia secondary to acromegaly in 1, alcohol abuse in 7 and obesity in 6. Conservative measures improved the disorder subjectively in 6 patients. One patient had a relapse 6 months after uvulopalatopharyngoplasty. 4 patients were successfully treated by nasal CPAP. Other diagnoses were idiopathic alveolar hypoventilation (2), Cheyne-Stokes breathing secondary to low cardiac output (1), monosymptomatic narcolepsy (2), sleep disturbances secondary to depression (2), chronic benzodiazepine abuse (1) and chronic bronchitis without nocturnal hypoxemia (1). History, clinical observation and oxymetry make diagnosis possible in most cases of OSAS severe enough to require treatment. Polysomnography is time-consuming and should be reserved for selected cases.


Asymmetric cell divisions in flowering plants - one mother, "two-many" daughters.
Plant development shows a fascinating range of asymmetric cell divisions. Over the years, however, cellular differentiation has been interpreted mostly in terms of a mother cell dividing mitotically to produce two daughter cells of different fates. This popular view has masked the significance of an entirely different cell fate specification pathway, where the mother cell first becomes a coenocyte and then cellularizes to simultaneously produce more than two specialized daughter cells. The "one mother - two different daughters" pathways rely on spindle-assisted mechanisms, such as translocation of the nucleus/spindle to a specific cellular site and orientation of the spindle, which are coordinated with cell-specific allocation of cell fate determinants and cytokinesis. By contrast, during "coenocyte-cellularization" pathways, the spindle-assisted mechanisms are irrelevant since cell fate specification emerges only after the nuclear divisions are complete, and the number of specialized daughter cells produced depends on the developmental context. The key events, such as the formation of a coenocyte and migration of the nuclei to specific cellular locations, are coordinated with cellularization by unique types of cell wall formation. Both one mother - two different daughters and the coenocyte-cellularization pathways are used by higher plants in precise spatial and time windows during development. In both the pathways, epigenetic regulation of gene expression is crucial not only for cell fate specification but also for its maintenance through cell lineage. In this review, the focus is on the coenocyte-cellularization pathways in the context of our current understanding of the asymmetric cell divisions. Instances where cell differentiation does not involve an asymmetric division are also discussed to provide a comprehensive account of cell differentiation.


Infrared Thermography in Surgery of Newly Diagnosed Glioblastoma Multiforme: A Technical Case Report.
Infrared thermography (IRT) is a real-time non-contact diagnostic tool with a broad potential for neurosurgical applications. Here we describe the intraoperative use of this technique in a single patient with newly diagnosed glioblastoma multiforme (GBM). An 86-year-old female was admitted in the clinic with a 2-month history of slowly progressing left-sided paresis. Neuroimaging studies demonstrated an irregular space-occupying process consistent with a malignant glioma in the right fronto-temporo-insular region. An elective surgical intervention was performed by using 5-aminolevulinic acid fluorescence (BLUE 400, OPMI) and intraoperative IRT brain mapping (LWIR, 1.25 mRad IFOV, 0.05°C NETD). After dura opening, the cerebral surface appeared inconspicuous. However, IRT revealed a significantly colder area (Δt° 1.01°C), well corresponding to the cortical epicenter of the lesion. The underlying tumor was partially excised and the histological result was GBM. Intraoperative IRT seems to be a useful technique for subcortical convexity brain tumor localization. Further studies with a large number of patients are needed to prove the reliability of this method in GBM surgery.


Oxidized low-density lipoproteins potentiate the mitogenic effect of 5-hydroxytryptamine on vascular smooth muscle cells.
Considerable attention has been focused on both highly oxidized low-density lipoprotein (ox-LDL) and mildly oxidized LDL (mox-LDL) as important risk factors for cardiovascular disease. Further, 5-hydroxytryptamine (5-HT) appears to play a crucial role in the development of atherosclerotic plaque. We assessed the interaction of oxidatively modified LDL and its major oxidative components, ie, hydrogen peroxide (H2O2), lysophosphatidylcholine (LPC), and 4-hydroxy-2-nonenal (HNE) with 5-HT on DNA synthesis in vascular smooth muscle cells (VSMCs). Growth-arrested rabbit VSMCs were incubated in serum-free medium with native LDL, mox-LDL, ox-LDL (all 50 ng/mL), H2O2 (0.5 microM), LPC (1 microM), or HNE (0.1 microM) for 24 hours followed by 5-HT (5 microM) for another 24 hours. DNA synthesis in VSMCs was measured by [3H]thymidine incorporation. Significant effects on [3H]thymidine incorporation were observed in VSMCs incubated with mox-LDL (129%), ox-LDL (129%), H2O2 (119%), LPC (115%), HNE (127%), or 5-HT (183%) in contrast with native LDL (113%). The mitogenic effect of 5-HT was potentiated by mox-LDL, ox-LDL, H2O2, LPC, or HNE (183 to 365%, 274%, 304%, 339%, or 273%, respectively) but not by native LDL (240%). The mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059 (10 microM) significantly inhibited the mitogenic effect of 5-HT but did not influence the effects of mox-LDL, ox-LDL, H2O2, LPC, or HNE. The intracellular antioxidant N-acetylcysteine (400 microM) significantly inhibited the mitogenic effects of mox-LDL, ox-LDL, H2O2, LPC, and HNE but not that of 5-HT. Our results suggest that mox-LDL, ox-LDL, and their major components H2O2, LPC, and HNE act synergistically with 5-HT in inducing VSMC DNA synthesis via MAPK and redox-sensitive pathways, contributing to the development of atherosclerotic plaque.


New B cell epitopes in the Plasmodium falciparum malaria circumsporozoite protein.
Most antibodies directed against the Plasmodium falciparum circumsporozoite (CS) protein react with its central domain, which contains about 40 repeats of the tetrapeptide Asn-Ala-Asn-Pro (NANP). To search for new epitopes in the non-repetitive part of the CS protein, we expressed the non-repetitive regions of the protein in E. coli as fusion proteins with mouse dihydrofolate reductase linked to six adjacent histidine residues. These fusion proteins were obtained at greater than 70% purity by a single Ni-chelate affinity chromatography step. Of the new epitopes defined in the C-terminal portion of the CS protein, three are located in a stretch of 65 amino acids immediately C-terminal of the protein's central repetitive domain. Pooled sera from inhabitants of a malaria-endemic area reacted with epitopes in this region of the molecule, and four mouse monoclonal antibodies to this region also reacted with the native CS protein on sporozoites. Two of the monoclonal antibodies reacted with a peptide PNDPNRNVD derived from a conserved region of the CS protein. The other two antibodies showed different reactivities to sporozoites of the NF54 and Ro59 parasite isolates. One, which reacted with a peptide ENANANNAV, recognized Ro59 but not NF54 sporozoites, while the other reacted with a small percentage of NF54 but not Ro59 sporozoites. Antibodies which react with non-repetitive regions of the CS protein could contribute to maintaining its genetic variability.


Fine needle aspiration cytology of pseudosarcomatous reactive lesions of soft tissues: A report of two cases.
Pseudosarcomatous lesions are reactive proliferative lesions of the soft tissue, that are likely to be misdiagnosed as malignant, based on clinical and histological features. The most common lesions are nodular fasciitis, proliferative fasciitis, proliferative myositis and myositis ossificans. These rapidly growing soft-tissue lesions can represent a variety of diagnoses involving radically different treatment modalities. Accurate diagnosis is important to avoid unnecessary and often mutilating surgery. We report two cases to illustrate the importance of correct identification of these lesions by fine needle aspiration cytology.


Pharmacotherapy of Insomnia and Current Updates.
Insomnia is highly prevalent and is associated with a range of psychological, psychiatric, and medical conditions. Insomnia affects health by influencing cognitive, emotional and social functioning. Circadian and sleep homeostatic processes play an important role in insomnia development and its maintenance. Several efficacious treatments, both pharmacologic and non-pharmacologic, exist for the management of insomnia. Among non-pharmacologic treatments including stimulus control therapy, sleep restriction, relaxation, sleep hygiene and cognitive therapy have been shown to be efficacious. Pharmacological treatment acts as adjuvant to cognitive behavioural treatment. Despite availability of various classes drugs for insomnia treatment, none can be considered as an ideal agent. Novel therapies are still being explored and tested to arrive at a hypnotic that has acceptable side effects and tolerability profile while still being efficacious.


Client-therapist intimacy: responses of psychotherapy clients to a consumer-oriented brochure.
Psychotherapy clients read two consumer-oriented brochures: a general brochure on psychology and a brochure on the topic of client-therapist intimacy. Half of the participants read the general brochure first and the brochure on client-therapist intimacy second, and half the participants did the reverse. Participants reported favorable reactions to the brochures, indicating they thought both should be made available to psychotherapy clients; that neither were too long, too sensitive, or too difficult to read; and that the brochures should be made available early during the therapeutic process. After reading the client-therapist intimacy brochure, participants also showed some changes in Likert-type scores measuring attitudes regarding intimate contact between clients and therapists. Although participants were more negative about issues of sexual misconduct after reading the client-therapist intimacy brochure, they did not indicate a decrease in trust of therapists, nor did they indicate a greater likelihood of filing a false complaint. We concluded that therapists' reservations about presenting clients with factual information regarding therapist sexual exploitation of clients are not empirically founded.


The metastatic potential of metastases: a case report.
Confirmation of the potential for metastases to metastasize in humans, especially those patients with a well controlled primary, should alter present approaches to patients with malignant disease and isolated recurrences. Reported herein is a case clearly demonstrating the metastatic potential of metastases.


MRI detection of single particles for cellular imaging.
There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 microm indicated that T(2)* effects can be readily detected from single MPIOs at 50-microm resolution and significant signal effects could be detected at resolutions as low as 200 microm. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into single-cell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging.


Effectiveness of aftercare program for suicide ideators: Real-world evidence from National Suicide Surveillance System in Taiwan.
Aftercare programs' effectiveness for suicide ideators has seldom been reported. This study assessed rates and factors related to the recurrence of suicide-related episodes after the index suicidal ideation episode, index cases, and family members receiving aftercare. This is a secondary data analysis of 1787 suicidal ideation episodes from 1557 individuals reported to the National Suicide Surveillance System in New Taipei City, Taiwan, from January 2012 to June 2013 and followed up until September 2013. Among 1787 index suicidal ideations, 19.1% had recurrences of suicide-related episodes, including suicidal ideation (11.9%), attempt (6.7%), and death (0.5%) within 2 years after index ideation. These recurrences were significantly reduced after the index cases received aftercare twice, three, and four or higher. Family members receiving aftercare twice or more were associated with reduced suicidality in the index cases. Receiving aftercare among index cases was associated with being a woman, suicide due to occupation/finance, and reporting from suicide hotlines. Receiving aftercare among family members was associated with the index cases aged ≤ 19 years old, suicide reasons related to school, occupation/finance, and reporting from schools and hospitals. Aftercare programs for suicide ideators and family members of adolescent suicide ideators (aged ≤ 19 years old) decreased subsequent episodes of suicidal behavior.


Treatment-failure tularemia in children.
Tularemia is an infection caused by Francisella tularensis. Its diagnosis and treatment may be difficult in many cases. The aim of this study was to evaluate treatment modalities for pediatric tularemia patients who do not respond to medical treatment. A single-center, retrospective study was performed. A total of 19 children with oropharyngeal tularemia were included. Before diagnosis, the duration of symptoms in patients was 32.15±17.8 days. The most common lymph node localization was the cervical chain. All patients received medical treatment (e.g., streptomycin, gentamicin, ciprofloxacin, and doxycycline). Patients who had been given streptomycin, gentamicin, or doxycycline as initial therapy for 10-14 days showed no response to treatment, and recovery was only achieved after administration of oral ciprofloxacin. Response to treatment was delayed in 5 patients who had been given ciprofloxacin as initial therapy. Surgical incision and drainage were performed in 9 patients (47.5%) who were unresponsive to medical treatment and were experiencing abcess formation and suppuration. Five patients (26.3%) underwent total mass excision, and 2 patients (10.5%) underwent fine-needle aspiration to reach a conclusive differential diagnosis and inform treatment. The causes of treatment failure in tularemia include delay in effective treatment and the development of suppurating lymph nodes.


Herbal medicine in the treatment of mental disorders.
During five thousand years of recorded history, we know that from the ancient times people have used different methods and procedures in treatment of different psychiatric disorders and very often these were medicinal preparations of plants. Numerous scientific discoveries and industrial age gave a big contribution to medicine development and significantly improved quality of life for psychiatric patients during the last century. However, evidence-based medicine after big bliss faced a lot of disappointments, and an attitude that some natural drugs were unnecessarily thrown out of use step by step came along. On the other hand, there are a huge number of patients that use natural medicinal plants in self-treatment of different psychiatric disorders. The aim of this article is not giving advantage to natural medicines over chemicals, nor to support self-treatment. The aim is to encourage thinking about the meaning of natural medicines in the treatment of mental disorders and an attempt of preventing to push them out totally into silence wherever it is justified and based on facts.


Economic Evaluation of Anesthesiology-Led Cardiac Implantable Electronic Device Service.
Implementation of an anesthesiology-led cardiac implantable electronic device (CIED) service can be viewed to have economic and efficiency challenges. This study evaluates the cost savings of an anesthesiology-led CIED service. A total of 830 patients presented in the pre-implementation period from 1 March 2016 to 31 December 2017, and 1981 patients presented in the post-implementation period from 1 January 2018 to 31 October 2021. Interrupted time-series analysis for single-group comparisons was used to evaluate the cost savings resulting from reduction in operating room (OR) start delays for patients with CIEDs. OR start-time delay was reduced by 10.6 min (95%CI: -20.5 to -0.83), comparing pre- to post-implementation. For an OR cost of USD 45/min, we estimated the direct cost to the department to be USD 1.68/min. The intervention translated into a total cost reduction during the intervention period of USD 250,000 (USD 18,000 to USD 470,000) per year for the institution and USD 9800 (USD 730 to USD 17,000) per year for the department. The yearly cost of employing a full-time team of CIED specialists would have been USD 135,456. The service triggered electrophysiology consultation on 13 device malfunctions. An anesthesiology-led CIED service resulted in substantial cost savings, increased OR efficiency and patient safety.


Twice exploration of tRNA +1 frameshifting in an elongation cycle of protein synthesis.
Inducing tRNA +1 frameshifting to read a quadruplet codon has the potential to incorporate a non-natural amino acid into the polypeptide chain. While this strategy is being considered for genome expansion in biotechnology and bioengineering endeavors, a major limitation is a lack of understanding of where the shift occurs in an elongation cycle of protein synthesis. Here, we use the high-efficiency +1-frameshifting SufB2 tRNA, containing an extra nucleotide in the anticodon loop, to address this question. Physical and kinetic measurements of the ribosome reading frame of SufB2 identify twice exploration of +1 frameshifting in one elongation cycle, with the major fraction making the shift during translocation from the aminoacyl-tRNA binding (A) site to the peptidyl-tRNA binding (P) site and the remaining fraction making the shift within the P site upon occupancy of the A site in the +1-frame. We demonstrate that the twice exploration of +1 frameshifting occurs during active protein synthesis and that each exploration is consistent with ribosomal conformational dynamics that permits changes of the reading frame. This work indicates that the ribosome itself is a determinant of changes of the reading frame and reveals a mechanistic parallel of +1 frameshifting with -1 frameshifting.


Reinforcing effect of discontinuous microglass fibers on resin-modified glass ionomer cement.
This study investigated the reinforcing effect of discontinuous-glass fiber fillers with different loading-fractions on selected mechanical properties and wear of resin-modified glass ionomer cement (RMGIC). Experimental fiber-reinforced RMGIC (Exp-RMGIC) was prepared by adding discontinuous-glass fiber of 200-500 µm in length to the powder of RMGIC (GC Fuji II LC) with different weight ratios (15, 20, 25 and 30 wt%). Mechanical properties and wear were determined for each experimental and control material. Scanning electron microscopy was used to evaluate the microstructure of the Exp-RMGICs. Wear pattern was analyzed by a three-dimensional (3D) noncontact optical profilometer. Fiber-reinforced RMGIC (30 wt%) had significantly higher mechanical performance of fracture toughness (1.9 MPa•m1/2), flexural strength (90.3 MPa), and diametral tensile strength (31 MPa) (p<0.05) compared to unreinforced material (0.8 MPa•m1/2, 51.9 and 20.7 MPa). The use of discontinuous-glass fiber fillers with RMGIC matrix is novel reinforcement and yielded superior toughening and flexural performance compared to conventional RMGIC.


[Correlation between fibrinogen polymorphisms and the type of cerebral infarction].
To study the association of beta-fibrinogen(Fg) gene -148 C/T and 448 G/A polymorphisms, plasma Fg concentration, molecular reactivity and the type of cerebral infarction. Gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The plasma Fg concentration and the molecular reactivity were also determined. The Fg concentration in MCI patients with T -148 allele was higher than that in PCI patients and controls. The MCI patients with A448 allele had higher Fg concentration, FMPV and FMPV/Amax when compared with controls, and had higher FMPV/Amax when compared with PCI patients. FgB beta -148 and 448 mutational genotypes have impact on Fg concentrationì and therefore increase the risk of MCI.


Exact Solution for the Interacting Kitaev Chain at the Symmetric Point.
The Kitaev chain model with a nearest neighbor interaction U is solved exactly at the symmetry point Δ=t and chemical potential μ=0 in an open boundary condition. By applying two Jordan-Wigner transformations and a spin rotation, such a symmetric interacting model is mapped onto a noninteracting fermion model, which can be diagonalized exactly. The solutions include a topologically nontrivial phase at |U|<t and a topologically trivial phase at |U|>t. The two phases are related by dualities. Quantum phase transitions in the model are studied with the help of the exact solution.


Potential of Epidermal Growth Factor-like Peptide from the Sea Cucumber Stichopus horrens to Increase the Growth of Human Cells: In Silico Molecular Docking Approach.
The sea cucumber is prominent as a traditional remedy among Asians for wound healing due to its high capacity for regeneration after expulsion of its internal organs. A short peptide consisting of 45 amino acids from transcriptome data of Stichopus horrens (Sh-EGFl-1) shows a convincing capability to promote the growth of human melanoma cells. Molecular docking of Sh-EGFl-1 peptide with human epidermal growth factor receptor (hEGFR) exhibited a favorable intermolecular interaction, where most of the Sh-EGFl-1 residues interacted with calcium binding-like domains. A superimposed image of the docked structure against a human EGF-EGFR crystal model also gave an acceptable root mean square deviation (RMSD) value of less than 1.5 Å. Human cell growth was significantly improved by Sh-EGFl-1 peptide at a lower concentration in a cell proliferation assay. Gene expression profiling of the cells indicated that Sh-EGFl-1 has activates hEGFR through five epidermal growth factor signaling pathways; phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), phospholipase C gamma (PLC-gamma), Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Ras homologous (Rho) pathways. All these pathways triggered cells' proliferation, differentiation, survival and re-organization of the actin cytoskeleton. Overall, this marine-derived, bioactive peptide has the capability to promote proliferation and could be further explored as a cell-growth-promoting agent for biomedical and bioprocessing applications.


Effect Of Cobalt-Chromium Alloy Re-Use In Dentistry On Its Castability Value.
Re-use of dental casting alloy is a routine practice, which is carried out with the motive to conserve resources. There have been studies on the re-use of alloys but a controversy exists as to the proportioning ratio of fresh to used alloy and the number of time an alloy can be recast. The objective of the study was to measure the effect of addition of 50% by weight used alloy to the fresh Cobalt-Chromium alloy on the castability. In the present in-vitro experimental study A total of 20 specimens were cast by flame centrifuge, using modified Whitlock's method. The total sample size was divided into four groups of five specimens each. Group 1 was the control group with 100% fresh alloy cast once. In group 2, 3 and 4, a 50% by weight cut off of previous castings were mixed to the fresh alloy. The reused alloy for the group 2 and 3 was further aged or exposed to flame casting separately. The number of completely cast segments were counted and castability value was calculated according to the Whitlock's formula. There was no significant difference of castability value among the entire tested group (p=0.085). Within the limitations of the present study, it is recommended that commercial Co-Cr-Mo alloy can be re-used six times without affecting its castability, when 50% fresh alloy is added on each re-use.


Alternative payment models and hospital engagement in health information exchange.
To assess whether hospital participation in alternative payment models (APMs) is associated with greater engagement in health information exchange (HIE) along 4 dimensions: volume of patients for whom information is exchanged, diversity of information types, breadth of partner types, and depth of technical approach. Pooled, cross-sectional analysis of data on US hospitals from 2014 to 2015. APM participation came from Leavitt Partners data, Medicare public use files, and the American Hospital Association (AHA) Annual Survey. We used Medicare data to measure HIE volume for 798 hospitals attesting to stage 2 Meaningful Use and the AHA Information Technology Supplement to measure HIE diversity, breadth, and depth for 1730 hospitals. We used mixed-effects regression to estimate the association between participation in APMs and each dimension of HIE. Compared with nonparticipating hospitals, full-year APM participation was associated with lower HIE volume (data were sent for 11 percentage points fewer discharges; P = .003), greater HIE diversity (of 4 data types, 0.3 more were transmitted; P <.001), greater HIE breadth (of 3 partner types, data were sent to 0.3 more; P <.001), and greater HIE depth (the odds of using a push and pull approach were 1.68 times greater; P = .004). Our finding that APM participation was associated with greater HIE diversity, breadth, and depth suggests that value-based payment may be spurring improvements in HIE infrastructure. However, our finding that APM participation is associated with lower HIE volume suggests that there may be an incentive to focus HIE investments on a limited number of partners.


Myosin IIA is required for cytolytic granule exocytosis in human NK cells.
Natural killer (NK) cell cytotoxicity involves the formation of an activating immunological synapse (IS) between the effector and target cell through which granzymes and perforin contained in lytic granules are delivered to the target cell via exocytosis. Inhibition of nonmuscle myosin II in human NK cells with blebbistatin or ML-9 impaired neither effector-target cell conjugation nor formation of a mature activating NK cell IS (NKIS; formation of an actin ring and polarization of the microtubule-organizing center and cytolytic granules to the center of the ring). However, membrane fusion of lytic granules, granzyme secretion, and NK cell cytotoxicity were all effectively blocked. Specific knockdown of the myosin IIA heavy chain by RNA interference impaired cytotoxicity, membrane fusion of lytic granules, and granzyme secretion. Thus, myosin IIA is required for a critical step between NKIS formation and granule exocytosis.


Hidden electrochemistry in the thermal grafting of silicon surfaces from grignard reagents.
Covalent grafting of alkyl chains on silicon can be obtained by thermal treatment in Grignard reagents. Alkyl halide present in the Grignard solution as an impurity appears to play a key role in the grafting process. Grafting efficiency is improved when the alkyl halide concentration is increased. It is also enhanced on n-type substrates as compared to p-type substrates and when alkyl bromides are present in solution rather than alkyl chlorides. The grafting reaction involves a zero-current electrochemical step. A reaction model in which simultaneous Grignard oxidation and alkyl halide reduction take place at the silicon surface accounts for all these observations. Alkyl halide reduction is the rate-determining step. Negative charging of the silicon surface lowers the energetic barrier for this reaction, allowing for efficient grafting on n-Si.


Determinants of perceived barriers to condom use among HIV-infected middle-aged and older African-American men.
This paper is a report of a study to describe which determinants best predict perceived barriers to condom use during sexual encounters among human immunodeficiency virus human immunodeficiency virus-infected African-American men, middle-aged and older, living in the United States of America. While the global epidemic of acquired immunodeficiency syndrome infection is a well-documented phenomenon with national and international implications, prevalence statistics indicate that middle-aged and older African-American (non-Hispanic) men have not benefited from the prevention efforts implemented during the past two decades. A cross-sectional design using a survey and convenience sampling was adopted between September 2003 and July 2004 to recruit n = 130 middle-aged human immunodeficiency virus-infected African-American men from infectious disease clinics from the Mid-Atlantic region in the United States of America. The survey covered demographics, perceived health beliefs, spiritual well-being and symptoms related to human immunodeficiency virus. Stepwise multiple regression showed having fewer human immunodeficiency virus-related symptoms associated with the human immunodeficiency virus (P = 0.004) and being single (P = 0.05) were perceived as barriers to condom use during sexual encounters (R(2) = 0.029, P = 0.046). Tailored interventions are needed for African-American men, middle-aged and older, infected with human immunodeficiency virus nationally and worldwide that are designed to decrease perceived barriers in order to increase condom use.


SPoRE: a mathematical model to predict double strand breaks and axis protein sites in meiosis.
Meiotic recombination between homologous chromosomes provides natural combinations of genetic variations and is a main driving force of evolution. It is initiated via programmed DNA double-strand breaks (DSB) and involves a specific axial chromosomal structure. So far, recombination regions have been mainly determined by experiments, both expensive and time-consuming. SPoRE is a mathematical model that describes the non-uniform localisation of DSB and axis proteins sites, and distinguishes high versus low protein density. It is based on a combination of genomic signals, based on what is known from wet-lab experiments, whose contribution is precisely quantified. It models axis proteins accumulation at gene 5'-ends with a discrete approximation of their diffusion and convection along genes. It models DSB accumulation at approximated gene promoter positions with intergenic region length and GC-content. SPoRE can be used for prediction and it is parameterised in an obvious way that makes it easy to understand from a biological viewpoint. When compared to Saccharomyces cerevisiae experimental data, SPoRE predicts axis protein and DSB positions with high sensitivity and precision, axis protein density with an average local correlation r = 0.63 and DSB density with an average local correlation r = 0.62. SPoRE outbreaks previous DSB predictors, which are based on nucleotide patterning, and it reaches 85% of success rate in DSB prediction compared to 54% obtained by available tools on a benchmarked dataset.SPoRE is available at the address http://www.lcqb.upmc.fr/SPoRE/.


Quantification of lung scintigrams.
A simple method of obtaining objective information consists in recording numerical information of the counts in each lung. Albumin macroaggregates labeled with 99Tc(m) and a gamma camera with a data processor were used.


Autoxidation of polyunsaturated fatty acids. Part I. Effect of ozone on the autoxidation of neat methyl linoleate and methyl linolenate.
Neat samples of polyunsaturated fatty acids were exposed to ozone in air in a flow system, and the formation of peroxides, conjugated dienes and thiobarbituric acid (TBA)-reactive material was followed as a function of time. The effect of ozone is to shorten the induction period normally observed in autoxidation studies, but the ozone, at the concentrations used here (0-1.5 ppm), appears to have no effect on the rates of product formation after the induction period. During the induction period, increasing ozone concentrations give rise to substantially increased rates of peroxide (or materials which titrate like peroxide) formation, a slightly increased rate of conjugated diene formation, and no significant increase in the rate of production of TBA-reactive material. Vitamin E lengthens the induction period but appears to have no other effect. Some of these data are in conflict with earlier reports of Menzel et al.


Acetaminophen induced pancreatitis.
This is the fourth reported case of acute pancreatitis associated with acetaminophen overdose. The patient had ingested the smallest amount of acetaminophen (9.75-13 g) that has been reported to produce acute pancreatitis. This patient also suffered liver and renal impairment and developed an ileus and ascites. Despite late therapy and laboratory tests that indicated a poor prognosis the patient made a complete recovery without sequelae.


Application of pie-crusting technique to facilitate closure of open abdomen after decompressive laparotomy.
We present the case of a 23-year-old man who developed abdominal compartment syndrome secondary to severe pancreatitis and required decompressive laparotomy and pancreatic necrosectomy. Despite application of a temporary abdominal closure system (ABThera Open Abdomen Negative Pressure Therapy), extensive retroperitoneal oedema and inflammation continued to contribute to loss of domain and prevented primary closure of the skin and fascia. The usual course of action would have involved reapplication of ABThera system until primary closure could be achieved or sufficient granulation tissue permitted split-thickness skin grafting. Though a safe option for abdominal closure, application of a skin graft would delay return to baseline functional status and require eventual graft excision with abdominal wall reconstruction for this active labourer. Thus, we achieved primary closure of the skin through the novel application of abdominal wall 'pie-crusting', or tension-releasing multiple skin incisions, technique.


Anti-Amyloid Aggregation Activity of Black Sesame Pigment: Toward a Novel Alzheimer's Disease Preventive Agent.
Black sesame pigment (BSP) represents a low cost, easily accessible material of plant origin exhibiting marked antioxidant and heavy metal-binding properties with potential as a food supplement. We report herein the inhibitory properties of the potentially bioaccessible fraction of BSP following simulated gastrointestinal digestion against key enzymes involved in Alzheimer's disease (AD). HPLC analysis indicated that BSP is transformed under the pH conditions mimicking the intestinal environment and the most abundant of the released compounds was identified as vanillic acid. More than 80% inhibition of acetylcholinesterase-induced aggregation of the β-amyloid Aβ1-40 was observed in the presence of the potentially bioaccessible fraction of BSP, which also efficiently inhibited self-induced Aβ1-42 aggregation and β-secretase (BACE-1) activity, even at high dilution. These properties open new perspectives toward the use of BSP as an ingredient of functional food or as a food supplement for the prevention of AD.


In situ SU-8 silver nanocomposites.
Nanocomposite materials containing metal nanoparticles are of considerable interest in photonics and optoelectronics applications. However, device fabrication of such materials always encounters the challenge of incorporation of preformed nanoparticles into photoresist materials. As a solution to this problem, an easy new method of fabricating silver nanocomposites by an in situ reduction of precursors within the epoxy-based photoresist SU-8 has been developed. AgNO3 dissolved in acetonitrile and mixed with the epoxy-based photoresist SU-8 forms silver nanoparticles primarily during the pre- and post-exposure soft bake steps at 95 °C. A further high-temperature treatment at 300 °C resulted in the formation of densely homogeneously distributed silver nanoparticles in the photoresist matrix. No particle growth or agglomeration of nanoparticles is observed at this point. The reported new in situ silver nanocomposite materials can be spin coated as homogeneous thin films and structured by using UV lithography. A resolution of 5 µm is achieved in the lithographic process. The UV exposure time is found to be independent of the nanoparticle concentration. The fabricated silver nanocomposites exhibit high plasmonic responses suitable for the development of new optoelectronic and optical sensing devices.


Influence of Variable Chloride/Sulfur Doses as Part of Potassium Fertilization on Nitrogen Use Efficiency by Coffee.
Chloride (Cl-) is applied in coffee at rates as a "macronutrient" in the form of muriate of potash (MOP). Potassium (K+) is one of the most demanded nutrients by the coffee plant, and MOP is one of the most used fertilizers in coffee production. No scientific evidence shows how Cl- applied with MOP influences coffee growth, nutrient uptake, and nitrogen use efficiency (NUE). In order to address these questions, a greenhouse trial over two years and a field trial over four years were conducted. The trials were designed to test the influence of variable Cl-/S ratios on biomass accumulation, nutrient uptake, and NUE. A significant effect of the Cl- rates on growth was observed under greenhouse conditions but a non-significant effect on yield under field conditions. Cl- and S significantly influenced the NUE in coffee. The results allow us to conclude that Cl- rates need to be balanced with S rates, and that Cl- applied at macronutrient rates can improve the NUE in coffee between 7 and 21% in greenhouse conditions and between 9% and 14% in field conditions, as long as the rates do not exceed 180 mg L-1 Cl- and 80 mg·L-1 S in the greenhouse and 150 kg·ha-1·year-1 Cl- and 50 kg ha-1·year-1 S in the field. With the aim to improve the NUE in coffee, the Cl- content in leaves in coffee should be lower than 0.33% of dry matter, and in soil lower than 30 mg·L-1. In practical terms, coffee farmers need to balance K-based fertilizers to avoid the excessive Cl- applications that reduce the nutrient use efficiency, especially the NUE.


Attitudes and observations about nonverbal communication in the psychotherapeutic greeting situation.
A survey of 209 licensed, psychotherapists was conducted to investigate attitudes towards and observations of nonverbal communication in a reference situation. Background factors such as gender, years of psychotherapeutic experience, hours of therapy practiced each month, and theoretical approach were used to examine relationships. The psychotherapeutic greeting situation, i.e., the first time a therapist and patient meet in a waiting room, was chosen as the reference situation. Female psychotherapists believed that nonverbal communication was more important than male psychotherapists. Psychotherapists with 16 years or more experience supported items that constitute the greeting phase and items on active observation significantly more often than psychotherapists with less experience. Hours of psychotherapeutic practice and frames of reference were not significantly related to any item within the questionnaire. Belief in nonverbal communication was not significantly related to items that involve preparing to meet a patient for the first time.


Covalent-bonded immobilization of lipase on poly(phenylene sulfide) dendrimers and their hydrolysis ability.
Covalent-bonded immobilization of lipase from burkholderia cepacia onto two poly(phenylene sulfide) (PPS) dendrimers with different generations (two and three) was achieved using carbodiimide as a coupling reagent. The hydrolysis activity of olive oil to fatty acid was studied on enzyme-immobilized PPS dendrimers. Enzyme activity was proportional to the enzyme loading, and highest recovered activity was obtained at the medium enzyme loading for both G2 and G3 dendrimers. The immobilization improved the optimum pH and caused the temperature range to widen. Immobilization of enzyme has enhanced the thermal stability of enzyme activity in comparison with free enzyme. The immobilized enzyme as a biocatalyst for batch hydrolysis of olive oil retained 80 approximately 90% activity even after 20 times of recycling. This retention of activity after recycle is very valuable and powerful in enzyme technology. The present noteworthy and vital availability on enzyme reaction of the covalently bonded immobilized lipase on dendrimer came from the structure of dendrimer with a large number of functional terminal groups, which are easily available for immobilization of many lipases at the situation keeping reactive enzymes on the surface of dendrimer.


Enhanced visible-light photocatalytic H2 production by Znx Cd1-x S modified with earth-abundant nickel-based cocatalysts.
The application of various earth-abundant Ni species, such as NiS, Ni, Ni(OH)2 , and NiO, as a co-catalyst in a Znx Cd1-x S system for visible-light photocatalytic H2 production was investigated for the first time. The loading of Ni or NiS enhanced the photocatalytic activity of Znx Cd1-x S because they could promote the electron transfer at the interface with Znx Cd1-x S and catalyze the H2 evolution. Surprisingly, Ni(OH)2 -loaded Znx Cd1-x S exhibits a very high photocatalytic H2 -production rate of 7160 μmol h(-1) g(-1) with a quantum efficiency of 29.5 % at 420 nm, which represents one of the most efficient metal sulfide photocatalysts without a Pt co-catalyst to date. This outstanding activity arises from the pronounced synergetic effect between Ni(OH)2 and metallic Ni formed in situ during the photocatalytic reaction. However, the loading of NiO deactivated the activity of Znx Cd1-x S because of their unmatched conduction band positions. This paper reports the optimization of the Znx Cd1-x S system by selecting an appropriate Ni-based co-catalyst, Ni(OH)2 , from a series of Ni species to achieve the highest photocatalytic H2 -production activity for the first time and also reveals the roles of these Ni species in the photocatalytic activity.


Engineered mosquitoes to fight mosquito borne diseases: not a merely technical issue.
Malaria, dengue and other mosquito-borne diseases pose dramatic problems of public health, particularly in tropical and sub-tropical countries. Historically, vector control has been one of the most successfully strategies to eradicate some mosquito-borne diseases, as witnessed by malaria eradication in Mediterranean regions such as Italy and Greece. Vector control through insecticides has been used worldwide; unfortunately, it is losing effectiveness due to spread of resistances. Control of mosquito-borne diseases through field-releases of genetically engineered mosquitoes is an innovative and now feasible approach. Genetically modified mosquitoes have already been released into the wild in some regions, and protocols for this release are on hand in others. Local authorities are vigilant that transgenic insects in the field are safe for human and animal populations, and the public engagement in every control program is assuming a central role.


Predictors of health service use over the palliative care trajectory.
Health system restructuring coupled with the preference of patients to be cared for at home has altered the setting for the provision of palliative care. Accordingly, there has been emphasis on the provision of home-based palliative care by multidisciplinary teams of health care providers. Evidence suggests that these teams are better able to identify and deal with the needs of patients and their family members. Currently there is a lack of literature examining the predictors of palliative care service use for various professional service categories. The purpose of this study was to examine the predictors of the propensity and intensity of five main health service categories in the last three months of life for home-based palliative care patients. This was a prospective cohort study. The predictors of service use were assessed using a two-part model, which treats the decision to use a service (propensity) and the amount of service use (intensity) as two distinct processes. Propensity was modeled using a logistic regression and intensity was modeled using ordinary least squares regression. The results indicate that each service category emerged with a different set of predictor variables. Common predictors of health service use across service categories were patient age and functional status. The results suggest that a consistent set of predictors across service categories does not exist, and thus the determinants of access to each service category are unique. These findings will help case managers, health administrators, and policy decision makers better allocate human resources to palliative patients.


Influence of Vitreomacular Adhesion on Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.
To investigate the effect of vitreomacular adhesion (VMA) on the outcome of antiangiogenic treatment for neovascular age-related macular degeneration (AMD). Ninety-nine eyes of 83 patients were used in our cohort study. We prospectively evaluated best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with neovascular AMD at baseline and 1, 2, 3, 6, and 12 months after treatment with anti-vascular endothelial growth factor (anti-VEGF) agents. All patients were stratified by spectral domain optical coherence tomography into 2 groups (i.e., VMA[+] and VMA[-]) according to the presence or absence of VMA, and the response to treatment was evaluated. Fifty-four eyes (54.5%) were included in the VMA(-) group and 45 eyes (45.5%) comprised the VMA(+) group. In paired comparisons of mean BCVA between baseline and each follow-up visit (1, 2, 3, 6, and 12 months), the VMA(-) group showed statistically significant improvement at 1, 2, and 3 months compared to baseline, and BCVA significantly improved only at 3 months in the VMA(+) group. For both groups, paired comparisons of CRT showed a statistically significant decrease when data obtained at 1, 2, 3, 6, and 12 months were compared to baseline values (p < 0.05). Posterior VMA is associated with a worse short-term outcome in patients with neovascular AMD treated with anti-VEGF agents.


Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy.
Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome-wide and long-range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCβ1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes.


Non-operative treatment of severe injuries to the medial and anterior cruciate ligaments of the knee.
We are reporting the results of conservative treatment of concomitant injuries to the medial collateral and anterior cruciate ligaments of the knee in twenty-eight patients (average age, twenty-eight years), who were followed for an average of three years. Twenty patients had a good or excellent result. Eleven of the fifteen patients who played contact sports and six of the nine who played non-contact sports returned to their preinjury levels of athletic activity. The older and nonathletic individuals had the poorest final results. We concluded that in many individuals with combined injury to the medial collateral and anterior cruciate ligaments, the knee responds well when treated conservatively.


[Application of multimodal anesthesia/analgesia in complex of anesthesiological support of reconstructive operations, performed on the lower extremity arteries].
Anesthesiological support of 47 patients, while performing reconstructive operations on the lower extremities arteries in presence of the third level of operative risk (according to ASA), was analyzed; of them in 24 - a spinal anesthesia was applied, in 23 - a reduced spino-epidural anesthesia. Application of a spino-epidural anesthesia/analgesia with reduction of the dose of a spinal component and usage of analgesia instead of anesthesia secures lesser intraoperative oscillations of hemodynamic indices in comparison with such while performing spinal anesthesia, as well as better antinociceptive protection, is also characterized by small toxic impact on the patient, demands application of a sedative and the infusion therapy of lesser volume. While performing a potentially complex and durable reconstructive operations on the lower extremities arteries a wide application of the method depicted is recommended.


Aetiological evaluation of chest pain in childhood and adolescence.
Chest pain, as a common cause of hospital admissions in childhood, necessitates detailed investigations due to a wide range of differential diagnoses. In this study, we aimed to determine the distribution of diseases causing chest pain in children and investigate the clinical characteristics of children with chest pain. This study included 782 patients aged between 3 and 18 years who presented to a paediatric cardiology outpatient clinic with chest pain between April 2017 and March 2018. Aetiological causes and demographic features of the patients were analysed. Most prevalent causes of chest pain were musculoskeletal system (33%) and psychogenic (28.4%) causes. Chest pain due to cardiac reasons was seen in eight patients (1%). Diseases of musculoskeletal and gastrointestinal systems and psychogenic disorders were significantly more common in male and female patients, respectively (p < 0.001 for all). In winter, patients' age and the number of patients with ≥12 years were higher than those in other seasons (p < 0.001). Most of the parents (70.8%) and patients (90.2%) thought that chest pain in their children was caused by cardiac causes. Most of the diagnoses for chest pain in childhood period are benign and include the musculoskeletal system and psychogenic diseases. Although chest pain due to cardiac diseases is rare, a comprehensive analysis of medical history, detailed physical examination and cardiac imaging with echocardiography is needed to reach more accurate diagnoses.


Content validation of a new measure of patient-reported barriers to antiretroviral therapy adherence, the I-Score: results from a Delphi study.
Over a third of people living with HIV (PLHIV) have suboptimal adherence to antiretroviral therapy (ART). Measures of barriers to ART adherence often lack comprehensiveness. To help manage ART adherence barriers in HIV care, we are developing a new patient-reported outcome measure (PROM) of these barriers (the I-Score). We assessed the content validity of 100 items (distinct barriers) to retain only those most relevant to both PLHIV and HIV health/social service providers. A web-based Delphi was conducted in Canada and France, collecting data from December 2018 to October 2019. Items were evaluated on relevance (the combined rated importance and actionability for HIV care of items among both PLHIV and providers); comprehensibility (rated item clarity); comprehensiveness (examined against our conceptual framework); cross-cultural equivalence (based on comparisons by questionnaire language (English, French) and country of residence). Pearson's chi-square tests were used for comparisons by language, country, gender, and stakeholder group (PLHIV, providers). Panelists included 40 PLHIV and 57 providers (66% response rate). Thirty-one items were retained based on consensus thresholds for relevance (minimum: 50% for PLHIV, 60% for providers) and showed good comprehensibility and comprehensiveness, when compared to our conceptual framework (representation of: 6/6 domains, 15/20 subdomains). No significant difference in relevance based on language or country was found among retained items, suggestive of cross-cultural equivalence. Among all 100 items, only 6 significant differences on relevance were observed for gender. For 62 items, the relevance ratings of PLHIV and providers differed significantly, with providers showing greater endorsement of all items but one. The Delphi led to a much-needed item reduction. Remaining items highlight the panel's multidimensional priorities for the PROM on ART adherence barriers, with few, if any, differences by language, country, and gender. While the analyses may lack generalizability and power, the sample size is considered adequate for a PROM validation study. Retained items showed good content validity. The different patterns of item endorsement observed underscore the utility of engaging multiple stakeholder groups in PROM development for use in clinical practice. The greater endorsement of items by providers versus patients merits further investigation, including the implications of such differentials for measure development.


Cell Magnetic Targeting System for Repair of Severe Chronic Osteochondral Defect in a Rabbit Model.
The aim of this study was to investigate a cell delivery system for repair of severe chronic osteochondral defects using magnetically labeled mesenchymal stem cells (m-MSCs), with the aid of an external magnetic device, through the accumulation of a small number of m-MSCs into a desired area and to detect the suitable number of autologous m-MSCs needed for repair of the defect. Twenty-six male Japanese white rabbits aged 6 months were used. An osteochondral defect was created bilaterally at the weight-bearing surface of the medial femoral condyle of the rabbits' knees (3 mm diameter; 4 mm depth). At 4 weeks after creation of the defect, autogenic transplantation of the m-MSCs into the defect area was performed, followed by 10-min exposure to an external magnetic device, where animals were divided into four groups: high (1 × 10(6) m-MSCs), medium (2 × 10(5) m-MSCs), low (4 × 10(4) m-MSCs), and control (PBS injection). At 4 and 12 weeks posttransplantation of m-MSCs, repaired tissue was assessed histologically using the Fortier score with toluidine blue staining. Transplantation of a low number of m-MSCs was not enough to improve osteogenesis and chondrogenesis, but the medium and high groups improved repair of the chronic defect with chondrogenic tissues and showed histologically significantly better results than the control and low groups. The use of a magnetic targeting system for delivering m-MSCs has the potential to overcome the clinical hurdles for repair of the severe chronic osteochondral defect. Furthermore, this system is predicted to produce good clinical outcomes for humans, not only to repair osteochondral defects but also to repair a variety of damaged tissues.


Isospora belli infection in a patient with Hodgkin's disease: report of a case.
A 42-year-old woman with a history of documented Hodgkin's disease for 1 year presented with watery diarrhea for 6 months. She developed watery diarrhea following recurrence of the underlying disease and use of herbs. After institution of chemotherapy, watery diarrhea persisted despite remission of the underlying disease. Stool cultures and examinations for several pathogens were negative. Later, oocysts of Isopora belli were identified in the stool. The immunological status was typical of patients with Hodgkin's disease. However, HTLV-1 seropositivity and an intact skin test for delayed hypersensitivity were noted. Institution of co-trimoxazole led to prompt resolution of the gastrointestinal symptoms within the ensuing 24 hours. Later she developed recurrent isosporiasis after chemotherapy for the underlying disease, but institution of co-trimoxazole again resolved the symptoms. She remains on maintenance therapy with co-trimoxazole. Isospora belli infection should be considered in opportunistic infections in patients with Hodgkin's disease.


Fluoride modulates preosteoblasts viability and matrix metalloproteinases-2 and -9 activities.
This study evaluated the influence of fluoride on cell viability and activity of matrix metalloproteinases (MMP) -2 and -9 secreted by preosteoblasts. Preosteoblasts (MC3T3-E1 murine cell line) were cultured in MEM medium supplement with 10% Fetal Bovine Serum (FBS) and nucleosides/ribonucleosides without ascorbic acid. Adherent cells were treated with different concentrations of F (as sodium fluoride-NaF) in medium (5 x 10(-6) M, 10(-5) M, 10(-4) M and 10(-3) M) for 24, 48, 72 and 96 h at 37ºC, 5% CO(2). Control cells were cultivated in MEM only. After each period, preosteoblast viability was assessed by MTT assay. MMP-2 and -9 activities were performed by gel zymography. Also, alkaline phosphatase (ALP) activity was quantified by colorimetry in all experimental groups. It was shown that cultured cells with the highest dose of F (10(-3) M) for 96 h decreased preosteoblast viability while lower doses of F did not alter it, when compared to untreated cells. No differences were observed in ALP activity among groups. Moreover, compared to control, the treatment of cells with F at low dose slightly increased MMP-2 and -9 activities after 24 h. It was concluded that F modulates preosteoblast viability in a dose-dependent manner and also may regulate extracellular matrix remodeling.


Improving Trauma Care in Africa.
Bringing the first Advanced Trauma Care for Nurses (ATCN) provider and instructor courses to Zimbabwe was the initial step in an educational partnership spanning more than 8,000 miles. Zimbabwe is a South African country with limited health care services, severe financial restraints, and a shortage of health care professionals. All of these barriers made our goal of bringing an organized and systematic approach to trauma care even more important. The nurses of Zimbabwe were aware that their patients were not receiving "best practice" care, which made them passionate for education, with strict enforcement of standardized delivery of care. The ATCN course provided the foundation for building a comprehensive approach to trauma care and creating a systematic and rapid initial assessment process during primary treatment of injured patients. Collaboration with the American College of Surgeons for the ATLS component was critical to the success and sustainability. The ultimate goal was to reduce morbidity and mortality from traumatic injuries and ultimately provide a sustained continuing education program to nurses countrywide. In November 2015, the Zimbabwe Nursing Council certified St. Philip's as its official National Nurse Trauma Training Center, the first and only center of its kind in Africa. As of October 2016, a total of 64 nurses have completed the ATCN courses and 9 have been checked off as ATCN faculty. Our goal was realized through the cooperation of many individuals. The nurses of Africa received the training crucial to delivering an excellent standard of care and ultimately saving lives.


[A Somali man with a painful thyroid mass: thyroid tuberculosis].
A 21-year-old man from Somalia presented with a painful mass in the thyroid, 6 months offatigue, weight loss and fever. Two separate courses of antibiotics did not improve his condition. Thyroid function tests were normal. The chest X-ray showed an enlarged hilus with some pulmonary infiltration around it. The diagnosis ofthyroid tuberculosis was established by cytological, microbiological and PCR testing of a fine needle aspirate of a thyroid lymph node. Treatment with antituberculosis agents resulted in a complete clinical response. The differential diagnosis of a painful thyroid mass encompasses subacute granulomatous thyroiditis, infectious thyroiditis, radiation- or trauma-induced thyroiditis and haemorrhage in the thyroid lymph nodes. Although thyroid tuberculosis is mainly a disease of developing countries, increasing immigration can lead to a higher incidence of this rare form of extrapulmonary tuberculosis and should therefore also be considered in patients with a painful thyroid mass.


A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study.
In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3 days to 11.5 months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.


An automatic CFD-based flow diverter optimization principle for patient-specific intracranial aneurysms.
The optimal treatment of intracranial aneurysms using flow diverting devices is a fundamental issue for neuroradiologists as well as neurosurgeons. Due to highly irregular manifold aneurysm shapes and locations, the choice of the stent and the patient-specific deployment strategy can be a very difficult decision. To support the therapy planning, a new method is introduced that combines a three-dimensional CFD-based optimization with a realistic deployment of a virtual flow diverting stent for a given aneurysm. To demonstrate the feasibility of this method, it was applied to a patient-specific intracranial giant aneurysm that was successfully treated using a commercial flow diverter. Eight treatment scenarios with different local compressions were considered in a fully automated simulation loop. The impact on the corresponding blood flow behavior was evaluated qualitatively as well as quantitatively, and the optimal configuration for this specific case was identified. The virtual deployment of an uncompressed flow diverter reduced the inflow into the aneurysm by 24.4% compared to the untreated case. Depending on the positioning of the local stent compression below the ostium, blood flow reduction could vary between 27.3% and 33.4%. Therefore, a broad range of potential treatment outcomes was identified, illustrating the variability of a given flow diverter deployment in general. This method represents a proof of concept to automatically identify the optimal treatment for a patient in a virtual study under certain assumptions. Hence, it contributes to the improvement of virtual stenting for intracranial aneurysms and can support physicians during therapy planning in the future.


[A bacteriological study on urinary calculi associated with infections].
There are difficult problems in the management of urinary calculi associated with infections. Stones associated with infections are not only infection stones such as struvite stones, but also other kinds of stones such as calcium oxalate. Therefore, from practical view points, bacteriological studies should be carried out on urinary calculi associated with infections as a whole. We investigated 120 cases of urinary calculi associated with infections with special reference to bacteria on the stone surface, within the stone, compositions of the stone and permeation of an antibiotic into the stone. Proteus was isolated most frequently from the urine, followed by E. coli and Pseudomonas. These bacteria were isolated from the stone surface, although the incidence of Proteus mirabilis was higher than that in the urine. Bacteria were isolated in 25 of the 33 specimens of the inside parts and in 12 of the 12 stones of MAP and MAP plus other components. Proteus mirabilis was found in 7 of the 12 stones. Bacteria were isolated from the inside of 9 of the 16 stones of CaP and CaP plus other components and Proteus mirabilis was found in 6 of these 9 cases. Pseudomonas was isolated in 2 out of the 7 stones of CaP plus CaOX and its growth was seen in 5 specimens. The incorporation of an antibiotic, Cefmetazole, into the stone differed greatly with each stone. There were some cases in which the concentration of Cefmetazole in the inside was less than 5% of that in the outside. Stones may function as a sanctuary for organisms and may protect these organisms.


A versatile variable-temperature scanning tunneling microscope for molecular growth.
We describe and discuss the design of a variable-temperature scanning tunneling microscope (STM) system for the study of molecules at temperatures between 18 and 300 K in ultrahigh vacuum. The STM head is a refinement of a very rigid design developed and successfully operated in Hamburg. In the current version, the head is connected to a liquid helium flow cryostat, thereby reaching a base temperature of 18 K. To minimize the heat load on the STM head, a helium back flow cooled radiation shield is installed. The dimensions and the choice of materials are based on simulations of the heat dissipation. The STM is galvanically isolated from the vacuum chamber to minimize electronic noise and mechanically decoupled by means of springs and an eddy current damping stage. Additionally, the design of the STM head allows the deposition of several molecular materials onto the same cold sample surface. The operation of the STM in imaging mode is demonstrated for TPP/Cu(111) and FePCNaClCu(111). Spectroscopic capabilities of the system are shown for electronic states on NaClCu(111) and TPP/Cu(111).


The role of internal auditing on corporate governance: its effects of economic and environmental performance.
Internal auditing has been an elementary and powerful component of corporate governance in business strategies. It is highly acknowledged as an important business control system in the realm of quality management. Business performance does not come by itself; it needs plenty of aids and capabilities. Existing studies have investigated the business performance with fewer outcomes in corporate sustainability, firm, and environmental performance. We present analysis and validated improvised hypothesis through structural equation modeling (SEM), using analysis of a moment structures (AMOS), on empirical evidence gathered from 304 Chief Executive Officer (CEOs) in Top Multinational Companies of Pakistan (TMCP). In this paper, we examine the role of internal audit functionality as an influencing factor via corporate governance in corporate sustainability, firm performance, and environmental performance. Moreover, business quality and performance are maintained using functions such as interests of shareholders, personnel and finance. Results suggest that internal audit functionality and corporate governance significantly influence corporate sustainability, firm performance, and environmental performance. Additionally, CEOs and top managers of TMCP are advised to concentrate on internal audit functionality with a mediating role of corporate governance that in turn encourages corporate sustainability, firm performance, and environmental performance.


Trivalent chromium induces autophagy by activating sphingomyelin phosphodiesterase 2 and increasing cellular ceramide levels in renal HK2 cells.
In this study, we examined the role of autophagy in the initiation of lipid increases in renal epithelial HK2 cells. We found that trivalent chromium [Cr(III)] induced autophagy by activating sphingomyelin phosphodiesterase 2 (SMPD2). SMPD2 increases levels of ceramide and other lipids. Confocal immunofluorescence microscopy showed that signals of ceramide overlapped with LC3, suggesting that ceramide might play an important role in the formation of autophagosome. In conclusion, our data indicate that Cr(III) induces autophagy via structural aberration of organelle membrane, in particular by the increase of lipid compositions in addition to autophagy-associated proteins.


Activation of intracellular serine proteinase in Bacillus subtilis cells during sporulation.
Cells of Bacillus subtilis 168 (trpC2) growing and sporulating in a single chemically defined medium carried out intracellular protein degradation and increased their levels of intracellular serine protease-1 in a manner very similar to what had previously been reported for cells sporulating in nutrient broth. The results were interpreted to mean that these processes are intrinsic to sporulation rather than medium dependent. To determine the cause of these increases in specific activity of proteinases, we purified the protease, prepared rabbit immunoglobulins directed against it, and monitored changes in protease antigen levels by performing rocket immunoelectrophoresis. In cells sporulating in nutrient broth, the protease antigen levels increased about 7-fold, whereas the specific activity increased about 150-fold, for an activation of about 20-fold. In cells sporulating in the single chemically defined sporulation medium, the protease antigen increased about 10-fold, whereas the specific activity increased at least 400-fold, for an activation of about 40-fold. These results were interpreted to mean that a posttranslational event activated the protease in vivo; a previously described endogenous proteinase inhibitor was confirmed to be present in the strain used. Chloramphenicol added to the cultures inhibited both the increases in antigen levels and in the specific activity of the proteinase.