Validation and ranking of seven staging systems of hepatocellular carcinoma.
The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0.731, 0.643, 0.754 and 0.622, respectively. When predicting 6-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.828, 0.729, 0.717, 0.692, 0.664, 0.746 and 0.575, respectively. For 3-month mortality, the prognostic value of CLIP ranked highest, followed by CIS; for 6-month mortality, the prognostic value of CLIP also ranked highest, followed by JIS. No significant difference between the AUCs of CLIP and CIS (P>0.05) in their predictive value for 3-month mortality was observed. The AUC of CLIP was significantly higher compared with that of the other staging systems (P<0.05) for predicting 6-month mortality. The χ2 values from the LRTs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 75.6, 48.4, 46.7, 36.0, 21.0, 46.8 and 7.24, respectively. The AIC values of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 1601.5, 1632.3, 1629.9, 1641.1, 1654.8, 1627.4 and 1671.1, respectively. CLIP exhibited the highest χ2 value and lowest AIC value, indicating that CLIP has the highest predictive value of cumulative survival rate. In the selected patients of the present study, CLIP was the staging system best able to predict 3- and 6-month and overall survival rates. CIS ranked second in predicting 3-month mortality.


A modification of the relative risk model with heterogeneity component for detecting genes contributing to longevity.
Genes associated with longevity can be identified on the basis of information on genotype frequencies for different age groups. This information is usually collected in population studies on aging. Significant age trends of genotype frequencies can indicate gene-longevity associations. Specific demographic data included in the model allows us to estimate the hazard and survival functions for different genotype groups. A new method based on the relative risk model makes it possible to dispense with some superfluous assumptions of this model and additionally to study the cohort effect and the effect of antagonistic pleiotropy.


Chronic suppurative osteomyelitis of the mandible: case report.
Osteomyelitis of the maxillofacial skeleton is rare in developed countries such as Australia. This case report describes the successful surgical treatment of chronic suppurative osteomyelitis (CSO) of the mandible in a 75 year old man. The precipitant factor was thought to be a retained tooth root in the (right) posterior body of the mandible. Treatment included a pre-surgical course of antibiotics (clindamycin 300mg, p.o. q.i.d. for two weeks) followed by removal of the retained root, surgical débridement of the affected bone, the intra-oral draining sinus, and resection of the cutaneous sinus tract. Specimens were taken for bacterial cultures and antibiotic sensitivity testing, and the resected tissue sent for histopathological review. On clinical and radiographic review at three months, the patient was well, completely symptom free and the osteomyelitis had fully resolved. This case report demonstrates the typical features of CSO. The combination of antibiotic therapy and surgical débridement was effective in the treatment of chronic suppurative osteomyelitis of the mandible utilizing intravenous sedation, and so averting the need for a general anaesthetic.


New mu-oxo octanuclear complexes of 3d elements stabilized by dialkylcarbamato ligands. Synthesis and X-ray crystal and molecular structures.
The octanuclear aggregates M(8)(mu(4)-O)(2)(O(2)CN(i)()Pr(2))(12) [M = Mn(II) 1, Co(II) 2, Ni(II) 3] have been prepared in good yields by controlled hydrolysis of the corresponding metal carbamate precursors [M(O(2)CN(i)()Pr(2))(2)](n)(). X-ray analysis has shown compounds 1-3 to be isostructural. The core of 2 contains two distorted [M(4)O] tetrahedra related by an inversion center. The hexanuclear carbamates M(6)(O(2)CNEt(2))(12) in toluene undergo a metal redistribution process with formation of the hexanuclear carbamates M'(x)M' '(6-x)(O(2)CNEt(2))(12), M' = Co, M' ' = Mn, as evidenced by mass-spectrometric data. In the presence of moisture, the mixed octanuclear carbamates Co(x)Mn(6-x)(MnO)(CoO)(O(2)CNEt(2))(12) were promptly formed and detected by DCI/MS measurements. Mass spectral data of Co(8)(mu(4)-O)(2)(O(2)CN(i)Pr(2))(12) are also reported.


T cells and reactive oxygen species.
Reactive oxygen species (ROS) have been long considered simply as harmful by-products of metabolism, which damage cellular proteins, lipids, and nucleic acids. ROS are also known as a weapon of phagocytes, employed against pathogens invading the host. However, during the last decade, an understanding has emerged that ROS also have important roles as signaling messengers in a multitude of pathways, in all cells, tissues, and organs. T lymphocytes are the key players of the adaptive immune response, which both coordinate other immune cells and destroy malignant and virus-infected cells. ROS have been extensively implicated in T-cell hyporesponsiveness, apoptosis, and activation. It has also become evident that the source, the kinetics, and the localization of ROS production all influence cell responses. Thus, the characterization of the precise mechanisms by which ROS are involved in the regulation of T-cell functions is important for our understanding of the immune response and for the development of new therapeutic treatments against immune-mediated diseases. This review summarizes the 30-year-long history of research on ROS in T lymphocytes, with the emphasis on the physiological roles of ROS.


Hollow MXene Spheres and 3D Macroporous MXene Frameworks for Na-Ion Storage.
2D transition metal carbides and nitrides, named MXenes, are attracting increasing attentions and showing competitive performance in energy storage devices including electrochemical capacitors, lithium- and sodium-ion batteries, and lithium-sulfur batteries. However, similar to other 2D materials, MXene nanosheets are inclined to stack together, limiting the device performance. In order to fully utilize MXenes' electrochemical energy storage capability, here, processing of 2D MXene flakes into hollow spheres and 3D architectures via a template method is reported. The MXene hollow spheres are stable and can be easily dispersed in solvents such as water and ethanol, demonstrating their potential applications in environmental and biomedical fields as well. The 3D macroporous MXene films are free-standing, flexible, and highly conductive due to good contacts between spheres and metallic conductivity of MXenes. When used as anodes for sodium-ion storage, these 3D MXene films exhibit much improved performances compared to multilayer MXenes and MXene/carbon nanotube hybrid architectures in terms of capacity, rate capability, and cycling stability. This work demonstrates the importance of MXene electrode architecture on the electrochemical performance and can guide future work on designing high-performance MXene-based materials for energy storage, catalysis, environmental, and biomedical applications.


Palm oil tocotrienols and plant flavonoids act synergistically with each other and with Tamoxifen in inhibiting proliferation and growth of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells in culture.
Palm oil, unlike many other dietary oils, does not increase the yield of chemically-induced mammary tumors in rats when fed at high levels in the diet. This difference appears to be due to the vitamin E fraction of palm oil, which is rich in tocotrienols, since palm oil stripped of this fraction does increase tumor yields. Experiments in our laboratory have shown that tocotrienols inhibit proliferation and growth of both MDA-MB-435 and MCF-7 cells in culture much more effectively than a-tocopherol. In addition, it was found that combinations of tocotrienols with Tamoxifen, a drug widely used for treatment of breast cancer, inhibit these cells more effectively than either tocotrienols or Tamoxifen alone. The present studies have now shown synergistic effects between tocotrienols and a number of other flavonoids from various plant sources, including citrus fruits, in the inhibition of both MDA-MB-435 and MCF-7 cells (IC50s 0.05-25 and 0.02-5 μg/mL respectively). In the MCF-7 cells, 1:1:1 combinations of tocotrienols, flavonoids and Tamoxifen were even more effective, with the best combination being d-tocotrienol, hesperetin and Tamoxifen (IC50 0.0005 μg/mL). These results suggest that diets containing palm oil may reduce the risk of breast cancer, particularly when eaten with other plant foods containing flavonoids, and may also enhance the effectiveness of Tamoxifen for treatment of breast cancer.


p38 MAP kinase regulates circadian rhythms in Drosophila.
The large repertoire of circadian rhythms in diverse organisms depends on oscillating central clock genes, input pathways for entrainment, and output pathways for controlling rhythmic behaviors. Stress-activated p38 MAP Kinases (p38K), although sparsely investigated in this context, show circadian rhythmicity in mammalian brains and are considered part of the circadian output machinery in Neurospora. We find that Drosophila p38Kb is expressed in clock neurons, and mutants in p38Kb either are arrhythmic or have a longer free-running periodicity, especially as they age. Paradoxically, similar phenotypes are observed through either transgenic inhibition or activation of p38Kb in clock neurons, suggesting a requirement for optimal p38Kb function for normal free-running circadian rhythms. We also find that p38Kb genetically interacts with multiple downstream targets to regulate circadian locomotor rhythms. More specifically, p38Kb interacts with the period gene to regulate period length and the strength of rhythmicity. In addition, we show that p38Kb suppresses the arrhythmic behavior associated with inhibition of a second p38Kb target, the transcription factor Mef2. Finally, we find that manipulating p38K signaling in free-running conditions alters the expression of another downstream target, MNK/Lk6, which has been shown to cycle with the clock and to play a role in regulating circadian rhythms. These data suggest that p38Kb may affect circadian locomotor rhythms through the regulation of multiple downstream pathways.


Analytic modelling of passive microfluidic mixers.
This paper deals with a new analytical model for microfluidic passive mixers. Two common approaches already exist for such a purpose. On the one hand, the resolution of the advection-diffusion-reaction equation (ADRE) is the first one and the closest to physics. However, ADRE is a partial differential equation that requires finite element simulations. On the other hand, analytical models based on the analogy between microfluidics and electronics have already been established. However, they rely on the assumption of homogeneous fluids, which means that the mixer is supposed to be long enough to obtain a perfect mixture at the output. In this paper, we derive an analytical model from the ADRE under several assumptions. Then we integrate these equations within the electronic-equivalent models. The resulting models computed the relationship between pressure and flow rate in the microfluidic circuit but also takes the concentration gradients that can appear in the direction perpendicular to the channel into account. The model is compared with the finite element simulation performed with COMSOL Multiphysics in several study cases. We estimate that the global error introduced by our model compared to the finite element simulation is less than 5% in every use case. In counterparts, the cost in terms of computational resources is drastically reduced. The analytical model can be implemented in a large range of modelling and simulation languages, including SPICE and hardware description language such as Verilog-AMS. This feature is very interesting in the context of the in silico prototyping of large-scale microfluidic devices or multi-physics devices involving microfluidic circuits, e.g. lab-on-chips.


Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review.
Scleroderma refers to an autoimmune connective tissue fibrosing disease, including three different subsets: localized scleroderma, limited cutaneous systemic sclerosis, and diffuse cutaneous systemic sclerosis with divergent patterns of organ involvement, autoantibody profiles, management, and prognostic implications. Although systemic sclerosis is considered the disease prototype that causes cutaneous sclerosis, there are many other conditions that can mimic and be confused with SSc. They can be classified into immune-mediated/inflammatory, immune-mediated/inflammatory with abnormal deposit (mucinoses), genetic, drug-induced and toxic, metabolic, panniculitis/vascular, and (para)neoplastic disorders according to clinico-pathological and pathogenetic correlations. This article reviews the clinical presentation with emphasis on cutaneous disease, etiopathogenesis, diagnosis, and treatment options available for the different forms of scleroderma firstly and for scleroderma-like disorders, including scleromyxedema, scleredema, nephrogenic systemic fibrosis, eosinophilic fasciitis, chronic graft-versus-host disease, porphyria cutanea tarda, diabetic stiff-hand syndrome (diabetic cheiroartropathy), and other minor forms. This latter group of conditions, termed also scleroderma mimics, sclerodermiform diseases, or pseudosclerodermas, shares the common thread of skin thickening but presents with distinct cutaneous manifestations, skin histology, and systemic implications or disease associations, differentiating each entity from the others and from scleroderma. The lack of Raynaud's phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies is also important diagnostic clues. As cutaneous involvement is the earliest, most frequent and characteristic manifestation of scleroderma and sclerodermoid disorders, dermatologists are often the first-line doctors who must be able to promptly recognize skin symptoms to provide the affected patient a correct diagnosis and appropriate management.


Peas (Pisum sativum L.).
In this chapter we describe a robust method for transformation of peas that has been successfully used in our laboratory since 1992. Using immature pea seed collected from field- or greenhouse-grown plants, we have produced transgenic lines for over 30 genotypes including named pea cultivars and advanced breeding lines. This method uses immature cotyledons as the explant, and the transformation efficiency is in the range 0.2 to 13.5% of cotyledons producing at least one independently transformed line. Agrobacterium tumefaciens strains AGL1 and KYRT1 are the most successful in our procedure, and kanamycin, phosphinothricin, and hygromycin are reliable selectable markers. Potentially useful genes have been introduced for pest and disease resistance, altering quality traits, and investigating metabolic pathways and are being studied in transgenic pea lines.


Boosted formic acid electro-oxidation on platinum nanoparticles and "mixed-valence" iron and nickel oxides.
The modification of Pt nanoparticles (nano-Pt, assembled electrochemically onto a glassy carbon (GC) substrate) with hybrid multivalent nickel (nano-NiOx) and iron (nano-FeOx) oxide nanostructures was intended to steer the mechanism of the formic acid electro-oxidation (FAO) in the desirable dehydrogenation pathway. This binary modification with inexpensive oxides succeeded in mediating the reaction mechanism of FAO by boosting reaction kinetics "electron transfer" and amending the surface geometry of the catalyst against poisoning. The sequence of deposition was optimized where the a-FeOx/NiOx/Pt/GC catalyst (where "a" denotes a post-activation step for the catalyst at -0.5 V in 0.5 mol L-1 NaOH) reserved the best hierarchy. Morphologically, while nano-Pt appeared to be spherical (ca. 100 nm in average diameter), nano-NiOx appeared as flowered nanoaggregates (ca. 56 nm in average diameter) and nano-FeOx (after activation) retained a plate-like nanostructure (ca. 38 nm in average diameter and 167 nm in average length). This a-FeOx/NiOx/Pt/GC catalyst demonstrated a remarkable catalytic efficiency (125 mA mgPt-1) for FAO that was ca. 12.5 times that of the pristine Pt/GC catalyst with up to five times improvement in the catalytic tolerance against poisoning and up to -214 mV shift in the FAO's onset potential. Evidences for equipping the a-FeOx/NiOx/Pt/GC catalyst with the least charge transfer resistance and the highest stability among the whole investigated catalysts are provided and discussed.


Polyglutamine-modulated striatal calpain activity in YAC transgenic huntington disease mouse model: impact on NMDA receptor function and toxicity.
Huntington disease (HD), caused by CAG expansion in the ubiquitously expressed huntingtin gene, is characterized by early dysfunction and death of striatal medium-sized spiny neurons (MSNs). Previous work has shown MSN-specific alterations in NMDA receptor (NMDAR) expression and cell death signaling. Furthermore, studies in HD human brain tissue and a knock-in mouse model demonstrate increases in calpain activity, which can be stimulated by NMDARs and contribute to excitotoxicity. Here, we report increased calpain activity in MSNs from the yeast artificial chromosome (YAC) transgenic mouse model of HD, expressing human full-length huntingtin with 128 polyglutamine repeats (YAC128), compared with wild type. Moreover, the calpain-cleaved product of NMDAR subunit NR2B is increased early, and NR2B expression levels are reduced, in YAC128 striatum. Although steady-state NMDAR surface expression is similar in wild-type and YAC128 MSNs, the rate of loss of NR2B-containing surface receptors is enhanced in YAC128 MSNs, suggesting that NMDAR forward trafficking to the surface is also faster, as previously reported for YAC72 MSNs. Calpain inhibitor-1 treatment normalized the loss rate of surface NMDARs in YAC128 MSNs to that of wild type, and significantly increased surface NMDAR expression in YAC128, but not in wild type or YAC72. With acute NMDAR overstimulation, the increase in calpain activity correlated with polyglutamine length, and calpain inhibitor treatment reduced NMDA-induced apoptosis in YAC72 and YAC128 MSNs to wild-type levels. Thus, the cumulative effect of increasing huntingtin polyglutamine length is to enhance MSN sensitivity to excitotoxicity at least in part by calpain-mediated cell death signaling.


Alterations of the intranucleolar DNA localization caused by simulated microgravity.
The functions of the nucleolus responsible for the biosynthesis of ribosomes in altered gravity are still unclear. The location of nucleolar DNA both in control and simulated microgravity with fluorescent and immunogold cytochemistry was investigated. We determined firstly the redistribution of rDNA in the nucleolar components accompanied with the changes in their ultrastructure. According to it, lowering the level of rDNA transcription in simulated microgravity was firstly proposed.


Nonlinear diffusion model for Rayleigh-Taylor mixing.
The complex evolution of turbulent mixing in Rayleigh-Taylor convection is studied in terms of eddy diffusivity models for the mean temperature profile. It is found that a nonlinear model, derived within the general framework of Prandtl mixing theory, reproduces accurately the evolution of turbulent profiles obtained from numerical simulations. Our model allows us to give very precise predictions for the turbulent heat flux and for the Nusselt number in the ultimate state regime of thermal convection.


Degradation of VX surrogate profenofos on surfaces via in situ photo-oxidation.
Surface degradation of profenofos (PF), a VX nerve gas surrogate, was investigated using in situ photo-oxidation that combines simple instrumentation and ambient gases (O2 and H2O) as a function of exposure conditions ([O3], [OH], UV light λ = 185 and/or 254 nm, relative humidity) and PF film surface density (0.38-3.8 g m(-2)). PF film 0.38 g m(-2) fully degraded after 60 min of exposure to both 254 and 185 nm UV light in humidified air and high ozone. The observed pseudo-first-order surface reaction rate constant (kobs = 0.075 ± 0.004 min(-1)) and calculated hydroxyl concentration near the film surface ([OH]g = (9 ± 2) × 10(7) molecules cm(-3)) were used to determine the second-order rate constant for heterogeneous reaction of PF and OH (k(OH)PF = (5 ± 1) × 10(-12) cm(3) molec(-1) s(-1)). PF degradation in the absence of 185 nm light or without humidity was lower (70% or 90% degradation, respectively). With denser PF films ranging from 2.3 to 3.8 g m(-2), only 80% degradation was achieved until the PF droplet was redissolved in acetonitrile which allowed >95% PF degradation. Surface product analysis indicated limited formation of the nontoxic phosphoric acid ester but the formation of nonvolatile chemicals with increased hydrophilicity and addition of OH.


Wolff-Parkinson-White syndrome and noncompaction in Leber's hereditary optic neuropathy due to the variant m.3460G>A.
This report describes a 66-year-old Caucasian male who acutely developed severe, bilateral impairment of visual acuity at 24 years of age. Leber's hereditary optic neuropathy (LHON) was suspected but the diagnosis was not genetically confirmed until the age of 49 years when the primary LHON mutation m.3460G>A was detected. Since onset, visual acuity had slightly improved. The family history was positive for LHON (brother, two sisters of mother, female cousin) and genetically confirmed in his brother and one aunt. Since the age of 65 years, he had experienced recurrent vertigo. His cardiological history was positive for arterial hypertension, noncompaction, myocardial thickening, intermittent right bundle-branch-block (RBBB) and Wolff-Parkinson-White (WPW) syndrome. In addition to LHON, he presented with polyneuropathy, hyperCKaemia, carotid artery occlusion, and a history of stroke. Cardiological investigations at 66 years of age revealed mildly reduced systolic function, enlarged atria, and nonsustained ventricular tachycardias. He underwent an electrophysiological investigation, but radiofrequency ablation was ruled out due to a 'bizarre' cardiac conduction system. Instead, an implantable cardioverter defibrillator was proposed but refused by the patient. Since the vertigo did not resolve it was attributed to polyneuropathy. This case demonstrates that LHON may be associated with noncompaction, myocardial thickening, reduced systolic function, enlarged atria, RBBB, WPW syndrome and nonsustained ventricular tachycardias. WPW syndrome in LHON may require invasive antiarrhythmic treatment.


Zeolitic imidazolate frameworks as intrinsic light harvesting and charge separation materials for photocatalysis.
Zeolitic imidazolate frameworks (ZIFs) are a subclass of metal organic frameworks that have attracted considerable attention in the past years and have found many applications including heterogeneous catalysis due to their highly ordered porous structure, large surface area, and structural flexibility. However, ZIFs are largely utilized as simple hosts or passive media for dispersing other catalytically active species, resembling the roles of zeolites in catalysis. In contrast, our recent findings show that ZIFs not only have broad absorption across the UV-visible and near IR spectral region but also have an exceptionally long-lived excited charge separated state, suggesting that ZIFs may be used as intrinsic light harvesting and photocatalytic materials rather than as inert hosts. This Perspective will focus on the recent progress on the fundamental studies of the intrinsic light absorption, charge separation, and photocatalytic properties of ZIFs and will discuss the outlook for future development.


[Unilateral Posterior Reversible Encephalopathy Syndrome after Ventriculo-Peritoneal Shunt for Normal Pressure Hydrocephalus Following Subarachnoid Hemorrhage: A Case Report].
The patient, a 79-year-old man, experienced a Hunt & Kosnik grade IV subarachnoid hemorrhage, presenting with sudden-onset coma and severe left hemiplegia. We performed cranial clipping surgery for a ruptured aneurysm on the right middle cerebral artery the same day. Post-operative recovery proceeded smoothly, with gradual improvements in disturbed consciousness and left hemiplegia. Three weeks post-operation, CT revealed low-density areas in the right frontal and temporal lobe, believed to be due to subarachnoid hemorrhage, as well as hydrocephaly. We then performed a lumbo-peritoneal (L-P) shunt for the hydrocephaly. Two months later, the patient experienced shunt occlusion, and we performed a ventriculo-peritoneal (V-P) shunt revision (pressure: 6 cm H(2)O). Headaches, severe decline in cognitive function, and worsened left hemiplegia were observed seven weeks post-shunt revision. Cranial CT revealed widespread low-density areas in right posterior cerebral white matter. We suspected unilateral posterior reversible encephalopathy syndrome (PRES) after performing cranial MRI and cerebral angiography. Increasing the set pressure of the shunt improved the symptoms and radiographic findings. PRES is typically bilateral, and unilateral incidents are rare. This is the first report of unilateral PRES secondary to shunt operation. Its unilaterality appears to have been caused by unilateral brain damage or adhesions to the brain surface from the subarachnoid cerebral hemorrhage. Overdrainage post-shunt can also induce PRES. Diagnosis of PRES is more difficult in unilateral cases;practitioners must keep PRES in mind as a rare complication post-shunt operation.


Understanding Molecular Aggregation of Ligand-Protected Atomically-Precise Metal Nanoclusters.
Monolayer-protected atomically precise nanoclusters (MPCs) are an important class of molecules due to their unique structural features and diverse applications, including bioimaging, sensors, and drug carriers. Understanding the atomistic and dynamical details of their self-assembly process is crucial for designing system-specific applications. Here, we applied molecular dynamics and on-the-fly probability-based enhanced sampling simulations to study the aggregation of Au25(pMBA)18 MPCs in aqueous and methanol solutions. The MPCs interact via both hydrogen bonds and π-stacks between the aromatic ligands to form stable dimers, oligomers, and crystals. The dimerization free energy profiles reveal a pivotal role of the ligand charged state and solvent mediating the molecular aggregation. Furthermore, MPCs' ligands exhibit suppressed conformational flexibility in the solid phase due to facile intercluster hydrogen bonds and π-stacks. Our work provides unprecedented molecular-level dynamical details of the aggregation process and conformational dynamics of MPCs ligands in solution and crystalline phases.


Gastroduodenal Surgery in Cirrhotic Patients - Case Series and Literature Review.
Specific risk factors for gastroduodenal surgery in cirrhotic patients have been identified, which dictates for a more personalized management. The retrospective study was conducted between 2012-2019 on twelve patients (7 cases of duodenal ulcer, 2 cases of gastric ulcer and 3 patients with gastric cancer). We took into account a number of possible factors involved in the unfavorable evolution of patients, based on data published in the literature so far. In order to follow the involvement of each factor we compared two groups of patients, one with unfavorable evolutions, exitus and another with favorable evolutions. Emergency surgery, the presence of ascites at the time of intervention, a higher than 30 MELD score, alcoholic cirrhosis, liver encephalopathy and liver failure are common factors that are found in a high percentage (between 75% and 100%) in patients who have had an unfavorable evolution, exitus. The same risk factors are found in much lower percentages in patients who have evolved favorably postoperatively, most between 12.5% and 25%. We analyzed preoperative aspects, surgical approach, complications and risk factors for these patients, compared them with the results of our study and identified future therapeutic possibilities. For CHILD B or C patients, the indication for surgery should be discussed in advance with a multidisciplinary team. Endoscopic submucosal dissection or discontinuation of D2 dissection should be considered in these patients.


Therapeutic pulpotomies in primary molars with the formocresol technique. A clinical and histological follow-up.
The results of therapeutic pulpotomies in primary molars with formocresol technique were studied by systematic follow-up. Of 84 primary lower molars in the clinical study, 56 became available for histological examination. The radiographic follow-up revealed periradicular osteitis in 10 per cent of the teeth treated. Internal root resorption was seen in 37 per cent of the teeth, or one-fifth of the roots treated. The histological examination revealed a very capricious diffusion of the medicament throughout the pulp tissue. Vital pulp remnants in the apical part of the treated roots showed no signs of healing. All pulps presented a varying number of inflammatory cells in the border zone adjacent to the formocresol-fixed region. In 80 per cent of the roots the histological sections revealed signs signs of internal resorption with or without incomplete repair tissue formation.


[Abdominal expression of the fetus in the 21st century].
Exercising pressure to the bottom of the uterus in different ways in order to accelerate the second period of giving birth is a widespread practice in the obstetrics departments of the country, which is generally not recorded in the history of the disease and in the rare cases when this is done it is indicated as "Kristeller method". Studies on the topic have been been published in various journals cited in Medline, Cochrane library, Nature, Science, Lancet, GyneWeb and others. Keywords used are: "Pressure, Fundal pressure, Expression abdominale, Obstetric Labor Complications, Kristeller maneuver second stage of labor". The author analyzes the literature on the benefit/harm of this practice in our time and recalls the original Kristeller method.


Preference for nitrogen versus oxygen donor coordination in uranyl- and neptunyl(VI) complexes.
The first actinyl phosphinimine complexes have been synthesized and, in the case of uranium, exhibit strong U-N interactions. Competition reactions clearly demonstrate a surprising preference for R3P=NH ligands over R3P=O in the system [AnO2Cl2(R3PX)2] (An = U(VI), Np(VI); R = Ph, Cy; X = O, NH). Spectroscopic evidence for N-donor coordination to [NpO2]2+ in solution indicates chemical similarities to the [UO2]2+ moiety.


Large-scale growth of well-aligned SiC tower-like nanowire arrays and their field emission properties.
Fabrication of well-aligned one-dimensional (1D) nanostrucutres is critically important and highly desired since it is the key step to realize the patterned arrays to be used as the display units. In the present work, we report the large-scale and well-aligned growth of n-type SiC nanowire arrays on the 6H-SiC wafer substrates via pyrolysis of polymeric precursors assisted by Au catalysts. The obtained n-type SiC nanowires are highly qualified with sharp tips and numerous sharp corners around the wire bodies, which bring the emitters excellent field emission (FE) performance with low turn-on fields (1.50 V/μm), low threshold fields (2.65 V/μm), and good current emission stabilities (fluctuation <3.8%). The work abilities of the n-type SiC tower-like nanowire arrays under high-temperature harsh environments have been investigated, suggesting that the resultant field emitters could be well serviced up to 500 °C. The temperature-enhanced FE behaviors could be attributed to the reduction of the work function induced by the rise of temperatures and the incorporated N dopants. It is believed that the present well-aligned n-type SiC tower-like nanowire arrays could meet nearly all stringent requirements for an ideal FE emitter with excellent FE properties, making their applications very promising in displays and other electronic nanodevices.


Endoscopic Techniques for Lumbar Interbody Fusion: Principles and Context.
Endoscopic techniques in spine surgery are rapidly evolving, with operations becoming progressively safer and less invasive. Lumbar interbody fusion (LIF) procedures comprise many spine procedures that have benefited from endoscopic assistance and minimally invasive approaches. Though considerable variation exists within endoscopic LIF, similar principles and techniques are common to all types. Nonetheless, innovations continually emerge, requiring trainees and experienced surgeons to maintain familiarity with the domain and its possibilities. We present two illustrative cases of endoscopic transforaminal lumbar interbody fusion with a comprehensive literature review of the different approaches to endoscopic LIF procedures.


Bioenergetics and diving activity of internesting leatherback turtles Dermochelys coriacea at Parque Nacional Marino Las Baulas, Costa Rica.
Physiology, environment and life history demands interact to influence marine turtle bioenergetics and activity. However, metabolism and diving behavior of free-swimming marine turtles have not been measured simultaneously. Using doubly labeled water, we obtained the first field metabolic rates (FMRs; 0.20-0.74 W kg(-1)) and water fluxes (16-30% TBW day(-1), where TBW=total body water) for free-ranging marine turtles and combined these data with dive information from electronic archival tags to investigate the bioenergetics and diving activity of reproductive adult female leatherback turtles Dermochelys coriacea. Mean dive durations (7.8+/-2.4 min (+/-1 s.d.), bottom times (2.7+/-0.8 min), and percentage of time spent in water temperatures (Tw) < or =24 degrees C (9.5+/-5.7%) increased with increasing mean maximum dive depths (22.6+/-7.1 m; all P< or =0.001). The FMRs increased with longer mean dive durations, bottom times and surface intervals and increased time spent in Tw< or =24 degrees C (all r2> or =0.99). This suggests that low FMRs and activity levels, combined with shuttling between different water temperatures, could allow leatherbacks to avoid overheating while in warm tropical waters. Additionally, internesting leatherback dive durations were consistently shorter than aerobic dive limits calculated from our FMRs (11.7-44.3 min). Our results indicate that internesting female leatherbacks maintained low FMRs and activity levels, thereby spending relatively little energy while active at sea. Future studies should incorporate data on metabolic rate, dive patterns, water temperatures, and body temperatures to develop further the relationship between physiological and life history demands and marine turtle bioenergetics and activity.


Comparative anti-inflammatory potential of crystalline and amorphous nano curcumin in topical drug delivery.
The problem of poor bioavailability and clinical efficacy of curcumin can be sorted out after converting crystalline Curcumin (CrysCur) into amorphous NanoCurcumin (NanoCur). Amorphous NanoCur was prepared by converting into nanoemulsion (o/w) using water titration method. The formulation were pre-screen by different physical stress tests, followed by in vitro release study, zeta potential, viscosity, transmittance, globule size distribution and ex vivo studies. The morphology of the NanoCur was determined using transmission electron microscopy (TEM) which revealed fairly spherical shape and good correlation with droplet size distribution study. The NanoCur was converted to gel using Cabopol 934. The composition of optimized NanoCur was curcumin (0.154% w/w), Carbopol 934 (0.702% w/w), ethanolic oil phase [ethanol (0.013% w/w): Capryol 90 (0.015%w/w)], Tween 20 (0.076%w/w) as surfactant, PEG 200 (0.038%w/w) as a co-surfactant and distilled water (q.s) as hydration phase. The steady state flux (Jss), permeability coefficient (Kp) and enhancement ratio (Er) of NanoCur gel was determined and compared with CrysCur gel. Anti-inflammatory effects of the formulations were evaluated in carrageenan-induced paw edema method in rats using Diclofenac as a reference. These ant-inflammatory effects of NanoCur was highly significant (p<0.001) compared to CrysCur and significantly (p<0.05) comparable with standard Diclofenac. The histology of the formulation treated skin showed insignificant changes in the integrity except in the group treated with NanoCur. The slight disruption in the integrity of skin may be because of surfactant present in the nano formulations. Short term storage stability showed insignificant changes in the droplet size and zeta potential, proving its high shelf-life. Finally, it was concluded that NanoCur could be a promising tool in the management of topical inflammation.


Removal of monomeric phenols in dry mill olive residue by saprobic fungi.
The dry olive residue (DOR) obtained from the olive oil extraction process has toxic components against plants and microorganism growth, particularly monomeric phenols. In this investigation nine saprobic fungi were found to be capable of completely removing these phenols from the solid after 20 weeks of growth, although the rate depended on the type of fungi and phenol. Results showed that most of the fungi tested first eliminated o-diphenols and then non-o-diphenols. However, some fungi did not follow this trend. Phanerochaete chrysosporium first removed hydroxytyrosol and tyrosol and later their glucosides and, in contrast, Paecylomyces farinosus hydrolyzed hydroxytyrosol and tyrosol glucosides at the first stage, 2 weeks of growth, and then eliminated all monomeric phenols. The behavior of this fungus seems of great interest for recovering phenolic antioxidants from the DOR. Similarly, differences in DOR decolorization capacity among the fungi tested were also observed. Coriolopsis rigida showed the highest capacity, followed by Phebia radiata, Pycnoporus cinnabarinus, and Pha. chrysosporium. Therefore, both decolorization and monomeric phenol elimination pointed out that saprobic fungi could be used to detoxify the DOR obtained from the two-phase system of the olive oil extraction process.


Applying sputum as a diagnostic tool in pneumonia: limited yield, minimal impact on treatment decisions.
We evaluated the role of sputum examination in the management of patients with community-acquired pneumonia (CAP) in a primary-care hospital without microbiologic laboratory facilities. A diagnostic strategy using regular collection of sputum samples, Gram staining in a local laboratory, and mailing of samples to a commercial laboratory for culture analysis. A 200-bed primary-care hospital without subspeciality physicians. One hundred sixteen consecutive patients with a diagnosis of CAP were prospectively evaluated during a 12-month period. Of 116 patients, 42 patients (36%) were capable of producing a sputum sample. Age > or = 75 years (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.18 to 0.93) and prior ambulatory antimicrobial treatment (OR, 3.2; 95% CI, 1.2 to 8.4) were independent predictors of sputum production. A delay in collection and processing of sputum samples of > 24 h was present in 31% and 39%, respectively. A delay in collection yielded an increased number of Gram-negative enteric bacilli and nonfermenters (44% vs. 7%, p = 0.056). A delay in processing was associated with an increased number of Candida spp isolates (33% vs. 9%, p = 0.16). The overall diagnostic yield was low (10 of 116 patients, 9%) due to a limited number of valid samples (n = 23 of 42 patients, 55%) and a limited number of definitely or probably positive samples on Gram's stain and culture (n = 10 of 42 patients, 24%). Prior ambulatory antimicrobial treatment was associated with a reduction in diagnostic yield (14% vs. 56%, p = 0.09). The impact of diagnostic results on antimicrobial treatment decisions was minimal, with antimicrobial treatment directed to diagnostic results in only one patient. We conclude that in this setting representative of primary-care hospitals in Germany, sputum had a low diagnostic yield and did not contribute significantly to patient management.


The Prognostic Impact of Determining Resection Margin Status for Multiple Colorectal Metastases According to the Margin of the Largest Lesion.
Although the prognostic role of surgical margin status after resection of colorectal liver metastasis (CRLM) has been previously examined, controversy still surrounds the importance of surgical margin status in patients with multiple tumors. Patients who underwent curative-intent surgery for CRLM from 2000 to 2015 and who presented with multiple tumors were identified. Patients with R1 resection status determined by the closest resection margin of the non-largest tumor were classified as R1-Type 1; patients with R1 status determined by the resection margin of the largest tumor were defined as R1-Type 2. Data regarding surgical margin status, size of tumors, and overall survival (OS) were collected and assessed. A total of 251 patients met inclusion criteria; 156 patients (62.2%) had a negative margin (R0), 50 had an R1-type 1 (19.9%), and 45 had an R1-type 2 (17.9%) margin. Median and 5-year OS in the entire cohort was 56.4 months and 48.0%, respectively. When all R1 (Type 1 + Type 2) patients were compared with R0 patients, an R1 was not associated with worse prognosis (P = 0.05). In contrast, when R1-type 2 patients were compared with R0 patients, an R1 was strongly associated with worse OS (P = 0.009). On multivariate analysis, although the prognostic impact of all R1 was not associated with OS (hazard ratio [HR] 1.56; P = 0.08), R1-Type 2 margin status independently predicted a poor outcome (HR 1.93; P = 0.03). The impact of margin status varied according to the size of the tumor assessed. While R1 margin status defined according to the non-largest tumor was not associated with OS, R1 margin status relative to the largest index lesion was associated with prognosis.


Nipping at cardiac remodeling.
Much of the mortality following myocardial infarction results from remodeling of the heart after the acute ischemic event. Cardiomyocyte apoptosis has been thought to play a key role in this remodeling process. In this issue of the JCI, Diwan and colleagues present evidence that Bnip3, a proapoptotic Bcl2 family protein, mediates cardiac enlargement, reshaping, and dysfunction in mice without influencing infarct size.


Delta agent infection: an unfavourable event in HBsAg positive chronic hepatitis.
To investigate the clinical value of delta agent infection in HBsAg positive chronic hepatitis, we detected anti-delta antibody (anti-delta) in serum and delta antigen (delta-Ag) on sequential liver biopsies of nine patients with HBsAg-positive CPH and 45 patients with HBsAg-positive CAH without cirrhosis observed for at least 2 years. The initial group of patients with CAH was composed of 54 patients who were consecutively either left untreated or treated with 15 mg of prednisolone daily. Nine patients dropped out. Delta-Ag was searched by the direct immunofluorescence technique. HBsAg, anti-delta, HBeAg and anti-HBe were detected by RIA. All CPH patients were delta-Ag negative in the 1st liver biopsy and anti-delta negative in serum. Out of these nine patients, seven remained delta-Ag negative CPH throughout the observation and the remaining two became delta-Ag positive, anti-delta positive and developed CAH. The 73% of patients with CAH were delta-Ag positive on the 1st biopsy and anti-delta positive in serum. The patients in the delta-Ag positive group (24 were always delta-Ag positive and two became delta-Ag positive during the observation) more frequently than those in the delta-Ag negative group (10 were always delta-Ag negative and nine became delta-Ag negative during the study) showed deterioration or died (77 vs. 16%; P less than 0.001). Neither in the delta-Ag positive group nor in the delta-Ag negative group did prednisolone modify the course of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Activation of platelets by autogenous vein grafts is not prevented by acetylsalicylic acid and dipyridamole.
We have shown previously that experimental autogenous vein grafts activate platelets for up to four months following operation. In the present study, animals were treated with middle dose ASA (10 mg X kg-1 X 24 h-1) plus dipyridamole (8 mg X kg-1 X 24 h-1) and followed for 8 months. Despite this treatment, platelets were activated by the vein graft for up to four months after operation but not after this time. Similarly, treatment with low dose ASA (0.5 mg X kg-1 X 24 h-1) plus dipyridamole (8 mg X kg-1 X 25 h-1), high dose ASA (40 mg X kg-1 X 24 h-1) plus dipyridamole (8 mg X kg-1 X 24 h-1), or dipyridamole alone (8 mg X kg-1 X 24 h-1), did not prevent the vein graft-induced activation of platelets. Full inhibition of platelet arachidonic acid metabolism was demonstrated in the high dose ASA plus dipyridamole group. These results suggest that the interaction between the vessel wall and platelet is not inhibited by ASA plus dipyridamole. Platelets have first to be activated before causing intimal hyperplasia. Since aspirin and dipyridamole did not prevent activation of platelets by the graft, this drug combination is unlikely to prevent the development of intimal hyperplasia in the graft wall.


Zonisamide for the treatment of epilepsy.
The availability of new antiepileptic drugs with different mechanisms of action has widened our therapeutic choice, allowing better tailoring of treatment regimens to address specific needs. Zonisamide is the latest addition to the pharmacological management of epilepsy in Europe, following extensive clinical experience in Japan and the USA. This article reviews the structure, mechanism of action, pharmacokinetics and drug interactions of zonisamide. The four double-blind, placebo-controlled trials in patients with drug-resistant focal seizures are also presented. They complement pre- and postmarketing studies conducted in Japan and provide clear-cut evidence that the drug has efficacy as an add-on treatment in this indication. Reports on zonisamide monotherapy and on the use of the drug for the control of several types of seizures (typical and atypical absences, tonic and myoclonic) and syndromes in children and adults are also commented on. These were all open-label studies, as is often the case with other antiepileptic drugs, dealing with treatment of epilepsy in children. The Japanese, US and European data provide a large database of safety information suggesting that the drug is well tolerated with mild-to-moderate adverse events (e.g., somnolence and dizziness). Nephrolithiasis appears to have a very low incidence and cutaneous reactions are rare. The available data provide an excellent foundation on which clinicians can build their knowledge on this drug, although the broad-spectrum efficacy of zonisamide needs to be confirmed through randomized trials.


A modular system to evaluate the efficacy of protease inhibitors against HIV-2.
The human immunodeficiency virus (HIV) protease is a homodimeric aspartyl protease that is crucial for the viral life-cycle, cleaving proviral polyproteins, hence creating mature protein components that are required for the formation of an infectious virus. With diagnostic measures and clinically used protease inhibitors focusing on HIV-1, due to its higher virulence and prevalence, studies of the efficacy of those inhibitors on HIV-2 protease remain widely lacking. Utilizing a wild-type HIV-2 vector backbone and cloning techniques we have developed a cassette system where the efficacy of clinically used protease inhibitors can be studied for various serotypes of HIV-2 protease both in enzymatic and cell culture assays. In our experiments, optimization of the expression protocol led to a relatively stable enzyme, for cell culture assays, the efficiency of transfection and transduction capability of the modified vector was tested and was not found to differ from that of the wild-type, moreover, a 2nd generation protease inhibitor was used to demonstrate the usefulness of the system. The combination of assays performed with our cassette system is expected to provide an accurate measure of the efficacy of currently used; as well as experimental protease inhibitors on HIV-2.


Epidemiology of penetrating injuries in the United Kingdom: A systematic review.
Penetrating injuries account for a significant number of deaths in the United Kingdom (UK) annually. Numerous articles have examined the epidemiology of penetrating trauma in various areas of the UK. This article aimed to systematically review the current literature and evaluate the incidence and mortality of penetrating injury according to region in the UK. A systematic literature search was performed using MEDLINE® (1946 to June 2016), EMBASE® (1974 to June 2016), and PsycINFO® (1806 to June 2016) databases. The following keywords were used in combination with Boolean operators: "epidemiology", "incidence", "frequency", "pattern", "distribution"; "penetrating"; "injuries", "injury", "trauma"; "United Kingdom", "UK", "England", "Scotland", "Wales", "London". Eleven relevant studies were identified across five regions of the UK. Study periods ranged from 3 months to 16 years and encompassed between 343 and 127,191 patients. Relative incidence within individual studies ranged from 0.3% (Midlands) to 21.0% (London) and mortality ranged from 0.5% (London) to 15.4% (Midlands). The majority of patients were young males. An extensive range of incidence and mortality rates were observed between studies in all regions. This was largely dependent on the study population under review. London was found to have the highest incidence of penetrating injuries, however these studies tended to focus on populations of trauma patients. The high proportion of male victims may reflect the risk of becoming involved in gangs and violence. Our ambiguous results indicate the need for further work directed towards the epidemiology of penetrating injuries within regional trauma networks.


Effects of protocol-driven care versus usual outpatient clinic care on survival rates in patients with type 2 diabetes.
To determine whether clinical outcomes in patients with type 2 diabetes were improved by protocol-driven care in a Diabetes Centre compared with usual outpatient care. Descriptive analysis of a prospective cohort. During a median 7-year observational period, 91 patients with type 2 diabetes and no cardiovascular or renal complications were monitored by a nurse and a diabetologist in a clinical trial setting according to a structured protocol. Another 81 patients with comparable clinical characteristics were monitored by generalists at the medical clinic in the same hospital. Clinical end points, defined as death and cardiovascular and renal events, were evaluated in 1997 by review of case records. Patients receiving structured care had lower mortality (relative risk [RR] = 0.21; 95% confidence interval [CI] = 0.07, 0.65; P = .006) than the usual-care group, as well as a lower incidence of combined clinical end points (RR = 0.43; 95% CI = 0.22, 0.84; P = .01). In the usual-care group, patients who had no monitoring of glycosylated hemoglobin or plasma lipid levels during the entire observational period (8.6%) had a 14.6-fold (P < .01) and 15.7-fold (P < .01) increased risk of death and combined clinical end points, respectively, compared with those who had at least one measurement (60.5%). Management by protocol-driven care model improved survival and clinical outcomes in patients with type 2 diabetes. Definitive studies are required to confirm these findings and compare the cost effectiveness of these care models.


Treatment of Nonclassic 11-Hydroxylase Deficiency with Ashwagandha Root.
An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3-β-ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.


Library orientation methods: J. Hillis Miller Health Center Library program.
Two orientation devices are described which are currently in use at the J. Hillis Miller Health Center Library. One is a taped tour which requires a portable recorder with earphones attached. Tapes are now available for nursing students, physical therapy students, and Health Center staff. The tour includes location information and description of the card catalog and certain basic index and abstract services. The second orientation device is a short instruction tape on the use of Index Medicus which is attached to the Index Medicus table. This is heard through a telephone apparatus. It is anticipated that the tape technique will be expanded to apply to other students and other library tools. It is also believed that this technique may be used in other libraries. Information about the supplies and equipment used is given as an addendum.


[Current news about epidemiology of syncytial respiratory virus infection].
At present, syncytial respiratory virus is the major agent of respiratory infections in pediatric patients. It can determine an important respiratory distress in particular children, as prematures with an gestational age <32 weeks, children affected by congenital heart diseases or bronchopneumonia dysplasia. In these patients, the prophylaxis with palivizumab is very important to prevent chronic pulmonary diseases.


Validation of Deep Learning-based Sleep State Classification.
Deep learning methods have been developed to classify sleep states of mouse electroencephalogram (EEG) and electromyogram (EMG) recordings with accuracy reported as high as 97%. However, when applied to independent datasets, with a variety of experimental and recording conditions, sleep state classification accuracy often drops due to distributional shift. Mixture z-scoring, a pre-processing standardization of EEG/EMG signals, has been suggested to account for these variations. This study sought to validate mixture z-scoring in combination with a deep learning method on an independent dataset. The open-source software Accusleep, which implements mixture z-scoring in combination with deep learning via a convolutional neural network, was used to classify sleep states in 12, three-hour EEG/EMG recordings from mice sleeping in a head-fixed position. Mixture z-scoring with deep learning classified sleep states on two independent recordings with 85-92% accuracy and a Cohen's κ of 0.66-0.71. These results validate mixture z-scoring in combination with deep learning to classify sleep states with the potential for widespread use.


Indoor air quality and acute lower respiratory infection in Indian urban slums.
The present prospective study was conducted at two urban slums of Delhi, Kusumpur Pahari and Kathputly Colony, in the peak winter season from November 1994 through February 1995. We studied 642 infants to determine the incidence of acute lower respiratory infection (ALRI) and its relationship to indoor air pollution due to fuel used for cooking (wood or kerosene). In Kusumpur Pahari, there were 317 children (142 wood and 175 kerosene), including 64 controls and 78 cases of ALRI in the wood fuel group and 81 controls and 94 ALRI cases in the kerosene group (p > 0.05). Out of 316 children in Kathputly Colony (174 wood and 142 kerosene), there were 33 and 45 ALRI cases in the wood and kerosene groups, respectively (p < 0.05). Controls were children without ALRI and were used as controls in different groups. The demographic data and risk factors, namely, nutritional and immunization status, were comparable in ALRI cases and controls in both study areas. Pneumonia was the most common ailment in all the groups. Bronchiolitis was reported in 22.5% of the wood group and 27.1% of the kerosene group in Kathputly Colony versus 13.7% in the wood group and 12.1% in the kerosene group in Kusumpur Colony. Only one case of croup was reported from Kusumpur Pahari among wood users. The duration of illness was longer in the Kusumpur Pahari due to poor compliance, feeding, and child rearing habits. In conclusion, a higher incidence of ALRI was reported in kerosene users in Kathputly Colony, a high pollution area; however, the reasons for the differences observed need further elucidation.


A low-cost microwell device for high-resolution imaging of neurite outgrowth in 3D.
Current neuronal cell culture is mostly performed on two-dimensional (2D) surfaces, which lack many of the important features of the native environment of neurons, including topographical cues, deformable extracellular matrix, and spatial isotropy or anisotropy in three dimensions. Although three-dimensional (3D) cell culture systems provide a more physiologically relevant environment than 2D systems, their popularity is greatly hampered by the lack of easy-to-make-and-use devices. We aim to develop a widely applicable 3D culture procedure to facilitate the transition of neuronal cultures from 2D to 3D. We made a simple microwell device for 3D neuronal cell culture that is inexpensive, easy to assemble, and fully compatible with commonly used imaging techniques, including super-resolution microscopy. We developed a novel gel mixture to support 3D neurite regeneration of Aplysia bag cell neurons, a system that has been extensively used for quantitative analysis of growth cone dynamics in 2D. We found that the morphology and growth pattern of bag cell growth cones in 3D culture closely resemble the ones of growth cones observed in vivo. We demonstrated the capability of our device for high-resolution imaging of cytoskeletal and signaling proteins as well as organelles. Neuronal cell culture has been a valuable tool for neuroscientists to study the behavior of neurons in a controlled environment. Compared to 2D, neurons cultured in 3D retain the majority of their native characteristics, while offering higher accessibility, control, and repeatability. We expect that our microwell device will facilitate a wider adoption of 3D neuronal cultures to study the mechanisms of neurite regeneration.


Phage Therapy in Poland - a Centennial Journey to the First Ethically Approved Treatment Facility in Europe.
Although phage discovery is an unquestionable merit of the English bacteriologist Frederick W. Twort and the Canadian-French microbiologist Félix d'Hérelle, who both discovered phages over 100 years ago, the Polish history of phage studies also dates back to those years. In contrast to the Western world, developing phage treatment in Poland has never been abandoned despite the country's tense history marked by the Second World War (WWII) and the communism era. Today, Poland takes a prominent and remarkable place in the phage research area. Furthermore, established in 2005, the Phage Therapy Unit at the Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, the first such center within European borders, has quickly become a model for other centers in the world facing the issue of widespread antibiotic resistance. This article constitutes an attempt to fill the gap in the scientific literature by providing a comprehensive summary of the long tradition of phage research in Poland.


Impact of persistence with infliximab on hospitalizations in ulcerative colitis.
To assess infliximab infusion patterns in ulcerative colitis (UC) and assess the impact of persistence with infliximab maintenance therapy on UC-related hospitalizations, lengths of stay, and inpatient costs. Retrospective analysis of medical claims for UC patients newly initiating infliximab treatment. Patients were aged >18 years and had 2 UC diagnosis codes, an infliximab index date between September 1, 2005, and January 31, 2008, and continuous enrollment for >12 months before and >14 months after the index date. Infliximab induction (first 56 days postindex) and maintenance (>56 days and <12 months postinduction) patterns were evaluated. Of patients with maintenance treatment, persistence was defined as a medication possession ratio (MPR) of >80%, and this group was compared with those without persistence (<80% MPR). Overall, 420 patients were included in the analysis; 84.3% (n = 354) continued to maintenance therapy. Maintenance infusion patterns were consistent with recommended prescribing information. A smaller proportion of patients with maintenance therapy persistence required hospitalization compared with patients without persistence (3.0% vs 20.4%; P <.001). Hospitalized patients with maintenance therapy persistence had significantly lower mean inpatient costs ($14,243 vs $32,745; P = .046), with a trend toward shorter mean lengths of stay (6.67 vs 9.71 days; P = .147) than patients without persistence. Infliximab maintenance therapy persistence in UC was associated with significantly fewer hospitalizations. Once hospitalized, patients with therapeutic persistence had significantly decreased inpatient costs.


Clinical manifestations, treatment outcome and post-operative complications of parotid gland tumours--an experience of 20 cases.
To find out clinical manifestations, treatment outcomes and post-operative complications of parotid gland tumours. The prospective quasi-experimental multi-centric study was conducted at three hospitals of Karachi -National Medical Centre, South City Hospital and Liaquat National Hospital, from July 2007 to July 2011, and comprised 20 patients who underwent surgery for tumour of the parotid gland. According to history, clinical examination and fine needle aspiration cytology findings, all cases appeared to be benign, so superficial parotidectomy was done in all the cases. There were 11 (55%) male and 9 (45%) female patients with a mean age of 53.2 +/- 2.8 years. All patients presented with progressively increasing lump in the parotid region with mean time duration of 2.2 +/- 2.8 years. Postoperative histopathological findings showed presence of pleomorphic adenoma in 18 (90%) cases and Warthin's tumour in 2 (10%). Post-operative complications included sensory deficit in 4 (20%) cases, temporary facial nerve paresis in 3 (15%), sialocoele in 2 (10%), post-operative bleeding and wound infection in 1 (5%) case each. No recurrence was noticed during follow-up which ranged between 6 months and 4 years. Surgery of the superficial parotid gland if performed carefully causes minimal complications.


Malnutrition-induced Wernicke's encephalopathy following a water-only fasting diet.
Wernicke's encephalopathy is a critical condition of neurological dysfunction resulting from a deficiency in thiamine. Chronic alcoholism is recognized as the most common cause of Wernicke's encephalopathy, but other causes, including fasting/starvation and malnutrition, have been documented within the scientific literature. These causes may not be readily recognized by healthcare professionals and may lead to Wernicke's encephalopathy being overlooked as a diagnosis when a nonalcoholic patient presents with classic signs and symptoms of the disorder. A narrative review of thiamine and its relationship to the development, diagnosis, and treatment of Wernicke's encephalopathy is presented based on a review of evidence-based guidelines and published research. To heighten awareness of the development of Wernicke's encephalopathy in fasted/starved and malnourished patients and to contribute to the scientific body of knowledge for the identification and management of Wernicke's encephalopathy in these patients, the clinical course and treatment of an adult woman who developed Wernicke's encephalopathy following a 40-day water-only fasting diet is outlined. Clinical suspicion was required to identify the patient's condition and initiate immediate intervention through parenteral thiamine administration. Oral thiamine supplementation of 100 to 800 mg per day for 6 months was required to aid recovery. The patient's clinical course and response to treatment illustrate the necessity for clinical awareness and suspicion of Wernicke's encephalopathy among healthcare professionals, timely and adequate parenteral thiamine administration, and oral thiamine supplementation at therapeutic doses to correct the nutrient deficiency, halt the progression of Wernicke's encephalopathy, and promote recovery.


[What is a normal thyroid function?]
Thyroid dysfunction is currently defined by a TSH value outside of its statistically established normal range. This definition does not take patients' individual symptoms or long-term risk of disease into account. However, increasing evidence shows that certain variations in thyroid function, even within the normal range, are associated with several adverse clinical outcomes. Also, subclinical thyroid dysfunction in patients, defined by a TSH outside of the normal range and free thyroxine within the normal range, has been shown to be accompanied by more thyroid-related symptoms when compared to the general population. This raises the question whether normal ranges are truly normal, and whether a new definition of thyroid function and thyroid dysfunction should be developed.


Functional interaction between the hippocampus and nucleus accumbens shell is necessary for the acquisition of appetitive spatial context conditioning.
The nucleus accumbens (NAc) has been implicated in a variety of associative processes that are dependent on the integrity of the amygdala and hippocampus (HPC). However, the extent to which the two subregions of the NAc, the core and shell, form differentiated circuits within the amygdala- and hippocampal-ventral striatal circuitry remains unclear. The present study investigated the effects of selective excitotoxic lesions of the nucleus accumbens shell or core subregion on appetitive elemental cue and context conditioning, shown previously to be dependent on the basolateral amygdala and hippocampus, respectively. Rats were trained sequentially to acquire discrete conditioned stimulus-sucrose conditioning, followed by spatial context-sucrose conditioning in a place preference apparatus characterized by three topographically identical chambers, the chambers being discriminable only on the basis of path integration. NAc shell lesions selectively impaired the acquisition of conditioned place preference and the use of spatial information to retrieve information about a discrete cue, whereas, as expected, NAc core lesions attenuated the acquisition of cue conditioning compared with sham rats. In a subsequent experiment, disconnection of the HPC from the NAc shell using unilateral asymmetric lesions of each structure resulted in a pattern of impairment in place conditioning and context-dependent cue retrieval similar to that produced by NAc shell lesions. These data not only suggest that the NAc core and shell subregions subserve distinct associative processes but also that the NAc shell and HPC are important functional components of a limbic corticostriatal network involved in spatial context conditioning.


Dermatology discharge continuity clinic enhances resident autonomy and insight into transitions-of-care competencies: a cross-sectional survey study.
Dermatology residents perform consults on hospitalized patients, but are often limited in their ability to follow-up with these patients after discharge, leading to inadequate follow-up and understanding of post-discharge transitions of care. In 2013, a discharge continuity clinic (DCC) staffed by the inpatient consult dermatology resident and attending dermatologist was established at one of the four adult hospital sites residents rotate through in the Harvard Combined Dermatology Residency Program. Resident perceptions about the DCC and their educational experience on inpatient consult rotations with a DCC and without a DCC were obtained using a cross-sectional survey instrument in June 2016. Self-reported data from a multi-year cohort of dermatology residents (n = 14 of 20, 70% response rate) reveals that the DCC enabled resident autonomy and resident satisfaction in care of their patients,insight into the disease-related challenges and the broader social context during transitions of care from inpatient to outpatient settings, and more enriching learning experiences than inpatient consult rotations without a DCC. Dermatology residents self-report participation in an inpatient consult rotation with aDCC supports their autonomy and achievement of post-discharge transitions-of-care competencies.


Hierarchical mutational events compensate for glutamate auxotrophy of a Bacillus subtilis gltC mutant.
Glutamate is the major donor of nitrogen for anabolic reactions. The Gram-positive soil bacterium Bacillus subtilis either utilizes exogenously provided glutamate or synthesizes it using the gltAB-encoded glutamate synthase (GOGAT). In the absence of glutamate, the transcription factor GltC activates expression of the GOGAT genes for glutamate production. Consequently, a gltC mutant strain is auxotrophic for glutamate. Using a genetic selection and screening system, we could isolate and differentiate between gltC suppressor mutants in one step. All mutants had acquired the ability to synthesize glutamate, independent of GltC. We identified (i) gain-of-function mutations in the gltR gene, encoding the transcription factor GltR, (ii) mutations in the promoter of the gltAB operon and (iii) massive amplification of the genomic locus containing the gltAB operon. The mutants belonging to the first two classes constitutively expressed the gltAB genes and produced sufficient glutamate for growth. By contrast, mutants that belong to the third class appeared most frequently and solved glutamate limitation by increasing the copy number of the poorly expressed gltAB genes. Thus, glutamate auxotrophy of a B. subtilis gltC mutant can be relieved in multiple ways. Moreover, recombination-dependent amplification of the gltAB genes is the predominant mutational event indicating a hierarchy of mutations.


Glycaemic response of proso millet-based (Panicum miliaceum) products.
The glycaemic response of millet foods and the effect of processing are not known. Therefore, decorticated proso millet was used to produce four types of common food products (biscuits, couscous, porridge and an extruded snack). Postprandial blood glucose response of these products (all containing 50 g of total starch) was compared to the same foods produced with refined corn, in a crossover human study with 12 healthy male participants (age 26.3 ± 3.8 yr; BMI 23.3 ± 2.8 kg/m2). Capillary blood samples were collected and glycaemic response was determined; differences were assessed using repeat measures ANOVA. Overall, the mean (±SEM) incremental area under the blood glucose response curve (mmol min/l) of the proso millet products was different from the corn products, but individual products (couscous = 66.7 ± 11.6, biscuit = 82.6 ± 13.7, extrudate = 198.7 ± 20.9, porridge = 40.1 ± 5.8) were not significantly lower (couscous = 43.5 ± 5.8, biscuit = 102.0 ± 10.3, extrudate = 198.7 ± 20.9, porridge = 52.2 ± 8.1) (p > .05). Glycaemic response of the products was not dependent on the grain type, but rather product matrix.


Comparative immunolocalization of GLUTs 1, 2, 3 and 5 in boar, stallion and dog spermatozoa.
Spermatozoa, as other eukaryotic cells, need hexoses to produce energy to maintain membrane homeostasis, to move along the female genital tract and to carry the male genome to the female gamete. GLUTs are a family of proteins that permit and improve the passive transport of hexoses inside cells. This study was aimed at investigating the presence and localization of GLUTs 1, 2, 3 and 5 in boar, stallion and dog spermatozoa by both immunofluorescence and western blotting. GLUTs exhibited a peculiar distribution along the sperm cell depending on the isoforms considered, the hexose they transport and the different species. The localization of GLUTs after capacitation and acrosome reaction highlighted the possible changes in their distribution because of the different functional moment. Only in dog spermatozoa changes in GLUTs distribution were demonstrated; these changes could be related to the different metabolic needs and modifications occurring in the sperm cell.


A Single Axial Slice of the Sternocleidomastoids and Paravertebral Muscles Associated with Worse Local Progression-Free Survival and Severe Toxicity in Sarcopenic Head and Neck Cancer Patients Undergoing Radiotherapy.
Objective The objective of this study is to contrast the predictive ability of targeted muscle groups as radiographic proxies of sarcopenia on computerized tomography (CT) with body mass index (BMI) in head and neck cancer patients (H&NCP) undergoing radiation at a safety net hospital, and to evaluate sarcopenia with survival, local progression, toxicities and treatment delays. Methods A retrospective review included 52 H&NCP treated between 2017-2019. The posterior neck muscles (PN), sternocleidomastoids (SCM), and their summed volume (AM) were contoured at C3 on patients' pre-treatment CT scans, then normalized to obtain skeletal muscle index (MI) values. Pre-treatment BMI was also evaluated. Cutoffs for sarcopenia were determined by receiver operating characteristic curves. Overall survival and local recurrence-free survival were evaluated by Kaplan-Meier. Acute grade 3 or higher toxicities were evaluated by binomial logistic regression. Results Using all neck muscles (AM-MI) produced the best model for predicting outcomes, outperforming individual muscle groups and BMI. Local progression-free survival was worse in sarcopenic patients at 25.81 months versus 35.40 months (p=0.026). Acute grade 3 or higher toxicities were associated with sarcopenia (p=0.005). Conclusions In this small, retrospective single-institution experience at a safety net hospital, a single axial slice of the combined sternocleidomastoids and paravertebral muscles at C3 performed better than either muscle group alone or pre-treatment BMI at predicting oncologic outcomes.


Cases in which ancestral maximum likelihood will be confusingly misleading.
Ancestral maximum likelihood (AML) is a phylogenetic tree reconstruction criteria that "lies between" maximum parsimony (MP) and maximum likelihood (ML). ML has long been known to be statistically consistent. On the other hand, Felsenstein (1978) showed that MP is statistically inconsistent, and even positively misleading: There are cases where the parsimony criteria, applied to data generated according to one tree topology, will be optimized on a different tree topology. The question of weather AML is statistically consistent or not has been open for a long time. Mossel et al. (2009) have shown that AML can "shrink" short tree edges, resulting in a star tree with no internal resolution, which yields a better AML score than the original (resolved) model. This result implies that AML is statistically inconsistent, but not that it is positively misleading, because the star tree is compatible with any other topology. We show that AML is confusingly misleading: For some simple, four taxa (resolved) tree, the ancestral likelihood optimization criteria is maximized on an incorrect (resolved) tree topology, as well as on a star tree (both with specific edge lengths), while the tree with the original, correct topology, has strictly lower ancestral likelihood. Interestingly, the two short edges in the incorrect, resolved tree topology are of length zero, and are not adjacent, so this resolved tree is in fact a simple path. While for MP, the underlying phenomenon can be described as long edge attraction, it turns out that here we have long edge repulsion.


Declining trend of Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant alleles after the withdrawal of Sulfadoxine-Pyrimethamine in North Western Ethiopia.
Antimalarial drug resistance is one of the major challenges in global efforts of malaria control and elimination. In 1998, chloroquine was abandoned and replaced with sulfadoxine/pyrimethamine, which in turn was replaced with artemether/lumefantrine for the treatment of uncomplicated falciparum malaria in 2004. Sulfadoxine/pyrimethamine resistance is associated with mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes. The prevalence of mutation in Pfdhfr and Pfdhps genes were evaluated and compared for a total of 159 isolates collected in two different time points, 2005 and 2007/08, from Pawe hospital, in North Western Ethiopia. The frequency of triple Pfdhfr mutation decreased significantly from 50.8% (32/63) to 15.9% (10/63) (P<0.001), while Pfdhps double mutation remained high and changed only marginally from 69.2% (45/65) to 55.4% (40/65) (P = 0.08). The combined Pfdhfr/Pfdhps quintuple mutation, which is strongly associated with sulfadoxine/pyrimethamine resistance, was significantly decreased from 40.7% (24/59) to 13.6% (8/59) (P<0.0001). On the whole, significant decline in mutant alleles and re-emergence of wild type alleles were observed. The change in the frequency is explained by the reduction of residual drug-resistant parasites caused by the strong drug pressure imposed when sulfadoxine/pyrimethamine was the first-line drug, followed by lower fitness of these resistant parasites in the absence of drug pressure. Despite the decrease in the frequency of mutant alleles, higher percentages of mutation remain prevalent in the study area in 2007/08 in both Pfdhfr and Pfdhps genes. Therefore, further multi-centered studies in different parts of the country will be required to assess the re-emergence of sulfadoxine/pyrimethamine sensitive parasites and to monitor and prevent the establishment of multi drug resistant parasites in this region.


Factors Associated With Success of Clinician-Researchers Receiving Career Development Awards From the National Institutes of Health: A Longitudinal Cohort Study.
Understanding the careers of recent career development awardees is essential to guide interventions to ensure gender equity and success in academic medicine. In 2010-2011 (T1) and 2014 (T2), 1,719 clinician-researchers who received new K08 and K23 awards in 2006-2009 were longitudinally surveyed. Multivariable analyses evaluated the influence of factors on success, including demographics, job characteristics, work environment, priorities, and domestic responsibilities. Of 1,275 respondents at T1, 1,066 (493 women; 573 men) responded at T2. Men and women differed in job characteristics, work environment, priorities, and domestic responsibilities. By T2, women had less funding (mean $780,000 vs. $1,120,000, P = .002) and published fewer papers (mean 33 vs. 45). Using a composite measure that considered funding, publications, or leadership to define success, 53.5% (264/493) of women and 67.0% (384/573) of men were successful. Gender differences in success persisted after accounting for other significant predictors-K award type, specialty, award year, work hours, funding institute tier, feeling responsible for participating in department/division administration, importance of publishing prolifically, feeling responsible for contributing to clinical care, importance of publishing high-quality research, collegiality of the mentoring relationship, adequacy of research equipment, and departmental climate. A significant interaction existed between K award type and gender; the gender difference in success was most pronounced among K23 researchers (among whom the odds ratio for females = 0.32). Men and women continue to have different experiences and career outcomes, with important implications for the design of interventions to promote equity and success.


Ginsenoside Rb1 attenuates homocysteine-augmented guidewire injury-induced intimal hyperplasia in mice.
Intimal hyperplasia (IH) is the primary cause for post-angioplasty restenosis. The purpose of this study is to investigate the effects of homocysteine (Hcy) and ginsenoside Rb1 (Rb1) on IH using a guidewire injury animal model. In 12-wk-old C57BL/6J mice, the left common carotid artery (CCA) was denudated with a guidewire and the right CCA was used as the uninjured control. They were treated with saline (NS), Hcy, Rb1, or Hcy + Rb1 for 4 wk prior to sacrifice. Animals were sacrificed at 4, 6, or 8 wk. Both CCAs were harvested and intimal-medium thickness (IMT) ratios were calculated. Local macrophage distribution was also studied. Histology analyses demonstrated consistent internal elastic lamina disruption and focal IH in the injured CCA segments. The degree of IH correlated to the lengths of time following injury. Hcy treated group had significant increase in IMT compared with the NS group (P < 0.05), while Rb1 group was similar to the NS group. In addition, Hcy + Rb1 group showed significant improvement in IMT compared with Hcy group (P < 0.01). Furthermore, Hcy significantly increased local macrophage content as compared with either lesion alone or Rb1 treated animals. Our study showed that Hcy increased the degree of IH and macrophage content in the injured CCA and that Rb1 attenuated these adverse effects. These changes might be mediated through antioxidative effects of Rb1. Our data suggests a potential clinical application of ginseng in controlling Hcy-related vascular injuries.


IV Magnesium Sulfate for Bronchiolitis: A Randomized Trial.
The goal of this study was to determine if IV magnesium, useful for severe pediatric asthma, reduces time to medical readiness for discharge in patients with bronchiolitis when added to supportive care. We compared a single dose of 100 mg/kg of IV magnesium sulfate vs placebo for acute bronchiolitis. Patients received bronchodilator therapy, nebulized hypertonic saline, and 5 days of dexamethasone if there was eczema and/or a family history of asthma. Time to medical readiness for discharge was the primary efficacy outcome. Bronchiolitis severity scores and need for infirmary or hospital admission and for clinic revisits within 2 weeks were secondary outcomes. Cardiorespiratory instability onset was the safety outcome. A total of 162 previously healthy infants diagnosed with bronchiolitis aged 22 days to 17.6 months (median, 3.7 months) were enrolled. Approximately one-half of patients had eczema and/or a family history of asthma; 86.4% had positive findings on nasopharyngeal virus swabs. Geometric mean time until medical readiness for discharge was 24.1 h (95% CI, 20.0-29.1) for the 78 magnesium-treated patients and 25.3 h (95% CI, 20.3-31.5) for the 82 patients receiving placebo (ratio, 0.95 [95% CI, 0.52-1.80]; P = .91). Mean bronchiolitis severity scores over time were similar for the two groups. The frequency of clinic visits in the subsequent 2 weeks (33.8% and 27.2%, respectively) was also similar. Fifteen magnesium recipients (19.5%) vs five placebo recipients (6.2%) were readmitted to the infirmary or hospital within 2 weeks (P = .016). No acute cardiorespiratory side effects were reported. IV magnesium did not provide benefit for patients with acute bronchiolitis and may be harmful. ClinicalTrials.gov; No.: NCT02145520; URL: www.clinicaltrials.gov.


[Effects of calcitonin on the pathology of spinal fusion in rabbit models].
To observe the effect of calcitonin on the pathology of fusion in lumbar posterior/facet spinal fusion in rabbit model. Thirty-two male New Zealand white rabbits were used to establish spinal fusion model. Sixteen rabbits received calcitonin at a dose of 1 IU x kg(-1) x d(-1) were classified as calcitonin group, and the remaining 16 rabbits as control group. Rabbits were killed 1, 2, 4, and 8 weeks after operations. Haematoxylin-eosin staining was applied to observe the pathological process of spinal fusion. Expression of bone morphogenetic protein-2 (BMP2) was detected by immunohistochemistry. Bone resorption and fibrovascular stroma formation were the main histological presentation 1 week after surgery. Two and 4 weeks after surgery, more cartilage formed with varying degrees of mineralization, while less trabeculae could be observed in the phase of active bone formation. No remarked margin was seen between cartilage and bone tissues. Eight weeks after surgery, trabeculae distributed widely. The pathological process of spinal fusion in calcitonin group was faster than in control group. Emery scores showed significant differences at different time points (F = 265.44, P < 0.001). Calcitonin and time had a positively synergistic effect on Emery scores, and calcitonin caused significant difference in terms of Emery scores since the second week (F = 22.43, P < 0.001). Expressions of BMP, were significantly different at different time points (F = 1186.54, P < 0.001). Also, calcitonin and time had a synergistic effect on BMP2 expression (F = 13.14, P < 0. 001). Endochondral ossification exists in the spinal fusion process and may be the main way of ossification. Calcitonin may stimulate the expression of BMP2 and thus accelerate the process of spinal fusion.


A new tangential gamma-ray spectrometer for fast ion measurements in deuterium and deuterium-tritium plasmas of the Joint European Torus.
A new tangential gamma-ray spectrometer has been developed for fast ion measurements in deuterium and deuterium-tritium plasmas of the Joint European Torus (JET). The instrument is based on a LaBr3 crystal with a photo-multiplier tube and replaces a pre-existing bismuth germanate detector, providing enhanced energy resolution and a counting rate capability in the MHz range. The line of sight is equipped with a LiH attenuator, which reduces the background due to 14 MeV neutron interactions with the crystal by more than two orders of magnitude and enables the observation of gamma-ray emission from confined α particles in JET deuterium-tritium plasmas. Thanks to its tangential line of sight, the detector can distinguish co- and counter-passing ions. The performance of the instrument is demonstrated through the results of recent JET fast ion experiments in deuterium plasmas.


Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma.
Chimeric antigen receptor (CAR) T-cell based immunotherapy has become a promising treatment mainly for hematological malignancies. Following the major success of CD19-targeted CAR, new potential targets for other malignancies are required. As such, B-cell maturation antigen (BCMA) is an attractive tumor-associated antigen to be targeted in multiple myeloma (MM). Herein, we aimed at assessing the function and optimal configuration of different BCMA-specific CAR, based on the same targeting moiety but with a different hinge and co-stimulatory domain. We compared their function to that of a previously characterized BCMA-CAR used in clinical trials. All constructs were expressed at high levels by primary human T cells and could trigger cytokine production and cytotoxicity upon co-culture with multiple myeloma targets. Nonetheless, critical differences were observed in off-target activation, exhaustion, and activation marker expression and in vivo antitumoral activity mediated by these different constructs. Interestingly, we noted that CD8-based hinge, combined with a 4-1BB intracellular domain, proved superior compared to IgG4-connecting regions, and/or a CD28-signaling moiety respectively. Overall, this study emphasizes the influence of CAR primary structure on its function and led to the identification of a highly efficient BCMA-specific CAR, namely H8BB, which displayed superior anti-tumoral activity both in vitro and long-term in vivo efficacy.


AS602801 treatment suppresses breast cancer metastasis to the brain by interfering with gap-junction communication by regulating Cx43 expression.
AS602801 has been reported as a potential drug candidate against brain metastasis by suppressing the gap-junction communication between lung cancer stem cells and astrocytes. In this study, we aimed to study the molecular mechanism underlying the role of AS602801 in the treatment of brain metastasis in breast cancer. We utilized female athymic BALB/c nude mice and MDA-MB-231/BT-474BR cells to establish experimental models. Polymerase chain reaction assays were performed to observe changes in the connexin 43 (Cx43) messenger RNA (mRNA) and c-Jun N-terminal kinase (JNK) mRNA levels. Dye transfer assay was used to observe the effect of AS602801 on cell-cell communication. An organotypic blood-brain barrier (BBB) model was utilized to observe the effect of AS602801 on transmigration through the BBB barrier. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and flow cytometry were performed to evaluate the proliferation and apoptosis of breast cancer cells co-cultivated with astrocytes. AS602801 inhibited the upregulation of Cx43 and JNK in brain metastasized breast cancer cells in a dose-dependent manner. Also, AS602801 significantly decreased the dye transfer rate from astrocytes to breast cancer cells, indicating the inhibitory effect of AS602801 on cell-cell communication. The transmigration ability of breast cancer cells co-cultured with astrocytes was decreased by AS602801. Furthermore, AS602801 reduced the elevated Cx43/JNK mRNA expression in the co-astrocyte group while suppressing the increased proliferation and promoting the decreased apoptosis of breast cancer cells co-cultivated with astrocytes. AS602801 also suppressed the brain metastasis of breast cancer cells and increased mouse survival. AS602801 downregulates the expressions of JNK and Cx43 to suppress the gap-junction activity. AS602801 also inhibits the communication between breast cancer cells and astrocytes, thus contributing to the treatment of brain metastasis in breast cancer.


[Purpura fulminans associated with varicella and polyvalent protective inoculations (author's transl)].
We report about a 10 5/12 years old boy, who developed the rare disease of Purpura fulminans following Varicella, after having received the trivalent Poliomyelitis vaccine of Sabin and a diphtheria-tetanus booster during the incubation period of Varicella. The acute stage of the disease was overcome by symptomatic therapy; extensive skin necrosis especially in the lower extremities had to be treated surgically. The etiology of Purpura fulminans has not yet been established. Since diffuse intravascular clotting (DIC) plays an essential part in the pathogenesis of this disease. Heparintherapy is now used as the treatment of choice. At the present state of knowledge we believe that the protective inoculations given in the incubation period of Varicella possibly provoced Purpura fulminans as a rare complication of Varicella.


Complicated migraine and migraine variants.
This article reviews the less frequently encountered varieties of migraine. It is suggested that these disorders be approached by evaluating possible underlying etiologies before positively diagnosing migraine. This decreases the likelihood of "missing" structural or metabolic disorders. The classification, diagnostic evaluation, differential diagnosis, and treatment options of these disorders is reviewed and a selection of references appended for additional information.


Diabetes knowledge among Greek Type 2 Diabetes Mellitus patients.
Diabetes knowledge has been shown to improve glycemic control and associate with several demographic parameters. In Greece, a country with high obesity rates, disease knowledge has never been evaluated in diabetic patients. This cross sectional study aimed to assess diabetes knowledge and its associations between social and demographic parameters, among Greek type 2 diabetes mellitus (T2DM) patients. One hundred fifty nine patients with T2DM were recruited from an urban and a rural clinic in Greece. Diabetes knowledge was assessed with the Brief Diabetes Knowledge Test (DKT). Basic anthropometry was performed. Data regarding glycemic control and sociodemographic characteristics were collected from the patients' medical files. Greek T2DM patients demonstrated poor disease knowledge (mean DKT score 8.3±2.2/14.0 and mean DKT as a percent of correct answers 59.6±15.8%). No differences were observed between sex, place of residence, or glycemic control, among subjects. Patients with higher education demonstrated greater diabetes knowledge. Simple obesity with concurrent central obesity or suboptimal glycemic control decreased diabetes knowledge among participants. Additionally, waist circumference was inversely correlated to diabetes knowledge. Based on the DKT, Greek patients exhibit poor diabetes knowledge. This study provides evidence for the need for better diabetes education in order to ameliorate disease outcome.


Severe Obstructive Sleep Apnea in a Child With Goldenhar Syndrome and Nasal Obstruction.
A 4-year-old boy with Goldenhar syndrome and severe obstructive sleep apnea does not tolerate nasal continuous positive airway pressure. Evaluation with imaging showed nasal obstruction with an inverted tooth. This case illustrates the importance of personalized evaluation and treatment plan in a child with Goldenhar syndrome.


Influence of heat treatments upon the mechanical properties and in vitro bioactivity of ZrO2-toughened MgO-CaO-SiO2-P2O5-CaF2 glass-ceramics.
Zirconia-toughened MgO-CaO-SiO2-P2O5-CaF2 glass-ceramics are prepared using sintering techniques, and a series of heat treatment procedures are designed to obtain a glass-ceramic with improved properties. The crystallization behavior, phase composition, and morphology of the glass-ceramics are characterized. The bending strength, elastic modulus, fracture toughness, and microhardness of the glass-ceramics are investigated, and the effect mechanism of heat treatments upon the mechanical properties is discussed. The bioactivity of glass-ceramics is then evaluated using the in vitro simulated body fluid (SBF) soaking test, and the mechanism whereby apatite forms on the glass-ceramic surfaces in the SBF solution is discussed. The results indicate that the main crystal phase of the G-24 sample undergoing two heat treatment procedures is Ca5(PO4)3F (fluorapatite), and those of the G-2444 sample undergoing four heat treatment procedures are Ca5(PO4)3F and β-CaSiO3 (β-wollastonite). The heat treatment procedures are found to greatly influence the mechanical properties of the glass-ceramic, and an apatite layer is induced on the glass-ceramic surface after soaking in the SBF solution.


Assessment of menopausal symptoms with changing hormone milieus in different menopausal transitional stages.
The present cross-sectional study is an attempt to evaluate menopausal symptoms with changing hormone milieus among women of different menopausal transitional stages. Out of all the symptoms, sexual dysfunction was the most commonly occurring symptom. Results of the correspondence analysis exhibited a significant association of symptoms like 'feeling unhappy', 'feeling dizzy', 'parts of body feeling numb' and 'muscle & joint pain' with late postmenopausal stage. Therefore, the assessment of menopausal health of women in rural settings of developing countries like India is of considerable significance for promoting their post reproductive health as well as for enhancing their quality of life.


A linkage disequilibrium perspective on the genetic mosaic of speciation in two hybridizing Mediterranean white oaks.
We analyzed the genetic mosaic of speciation in two hybridizing Mediterranean white oaks from the Iberian Peninsula (Quercus faginea Lamb. and Quercus pyrenaica Willd.). The two species show ecological divergence in flowering phenology, leaf morphology and composition, and in their basic or acidic soil preferences. Ninety expressed sequence tag-simple sequence repeats (EST-SSRs) and eight nuclear SSRs were genotyped in 96 trees from each species. Genotyping was designed in two steps. First, we used 69 markers evenly distributed over the 12 linkage groups (LGs) of the oak linkage map to confirm the species genetic identity of the sampled genotypes, and searched for differentiation outliers. Then, we genotyped 29 additional markers from the chromosome bins containing the outliers and repeated the multilocus scans. We found one or two additional outliers within four saturated bins, thus confirming that outliers are organized into clusters. Linkage disequilibrium (LD) was extensive; even for loosely linked and for independent markers. Consequently, score tests for association between two-marker haplotypes and the 'species trait' showed a broad genomic divergence, although substantial variation across the genome and within LGs was also observed. We discuss the influence of several confounding effects on neutrality tests and review the evolutionary processes leading to extensive LD. Finally, we examine how LD analyses within regions that contain outlier clusters and quantitative trait loci can help to identify regions of divergence and/or genomic hitchhiking in the light of predictions from ecological speciation theory.