Predicting the anion conductivities and alkaline stabilities of anion conducting membrane polymeric materials: development of explainable machine learning models.
Anion exchange membranes (AEMs) are core components in fuel cells and water electrolyzers, which are crucial to realize a sustainable hydrogen society. The low anion conductivity and durability of AEMs have hindered the commercialization of AEM-based devices, and research and development (R&D) to improve AEM materials is often resource-intensive. Although machine learning (ML) is commonly used in many fields to accelerate R&D while reducing resource consumption, it is rarely used in the AEM field. Three problems hinder the adoption of ML models, namely, the low explainability of ML models; complication with expressing both homopolymers and copolymers in unity to train a single ML model; and difficulty in building a single ML model that comprehends various polymer types. This study presents the first ML models that solve all three problems. Our models predicted the anion conductivity for a diverse set of unseen AEM materials with high accuracy (root mean squared error = 0.014 S cm-1), regardless of their state (freshly synthesized or degraded). This enables virtual pre-synthesis screening of novel AEM materials, reducing resource consumption. Moreover, human-comprehensible prediction logic revealed new factors affecting the anion conductivity of AEM materials. Such capability to reveal new important variables for AEM materials design could shift the paradigm of AEM R&D. This proposed method is not limited to AEM materials, instead it presents a technology that is applicable to the diverse set of polymers currently available.


Comparative study between fully tethered and free swimming at different paces of swimming in front crawl.
Tethered swimming is a method often used to measure or enhance the physical and technical resources of swimmers. Although it is highlighted that the technique used in tethered swimming is probably different from that used in free conditions, there are few comparative studies on this subject. The current study aims to compare fully tethered and free swimming based on kinematic hand parameters (orientation, velocity and acceleration of the hand, sweepback and angle of attack), which are known to act directly on the generation of propulsive forces. The results show that there are significant differences during the stretch and catch phases but less during the insweep and upsweep phases. Tethered swimming makes it possible to estimate the propelling forces generated by the hand in free swimming at distance and middle-distance paces, but overestimates it at sprint pace. However, in view of the modifications of the kinematic parameters, it should not be used under repeated conditions of use, such as for the development of swimmers' capacity.


Disruptive innovation in academic medical centers: balancing accountable and academic care.
Numerous academic medicine leaders have argued that academic referral centers must prepare for the growing importance of accountability-driven payment models by adopting population health initiatives. Although this shift has merit, execution of this strategy will prove significantly more problematic than most observers have appreciated. The authors describe how successful implementation of an accountable care health strategy within a referral academic medical center (AMC) requires navigating a critical tension: The academic referral business model, driven by tertiary-level care, is fundamentally in conflict with population health. Referral AMCs that create successful value-driven population health systems within their organizations will in effect disrupt their own existing tertiary care businesses. The theory of disruptive innovation suggests that balancing the push and pull of academic and accountable care within a single organization is achievable. However, it will require significant shifts in resource allocation and changes in management structure to enable AMCs to make the inherent difficult choices and trade-offs that will ensue. On the basis of the theories of disruptive innovation, the authors present recommendations for how academic health systems can successfully navigate these issues as they transition toward accountability-driven care.


Emerging role of carbon monoxide in regulation of cellular pathways and in the maintenance of gastric mucosal integrity.
Heme oxygenase (HO) catalyzes the degradation of toxic free heme to the equimolar amounts of biliverdin, Fe2+ and concurrently releases of carbon monoxide (CO). CO is nowadays increasingly recognized as an important signaling molecule throughout the body that is involved in many physiological processes and shows multidirectional biological activity. Recent evidence indicates that CO exhibits the anti-inflammatory, anti-proliferative, anti-apoptotic, anti-aggregatory and vasodilatory properties. The cellular mechanisms underlying the activity of CO involve stimulation of cGMP-dependent signaling pathway and large conductance calcium activated K+ channels, the activation of mitogen-activated protein kinases and the nuclear factor k-light chain-enhancer of activated B cells transcription factor pathway. Stimulation of endogenous CO production by HO inducers or the inhalation of CO or the delivery of this gaseous molecule by novel pharmaceutical agents have been found in experimental animal models to be promising in the future therapy of various diseases. CO appears to act as a significant component of the complex mechanism of gastrointestinal (GI) mucosal defense. This gaseous molecule plays an important role in diabetic gastroparesis, prevention of the upper GI mucosal damage, post-operative ileus and the healing of ulcerative colitis. This review focuses on the better understanding mechanisms through which CO contributes to the mechanism of protection, resistance to injury and ulcer healing. It is becoming apparent that the pleiotropic effect of this molecule may increase clinical applicability of CO donors and their implementation in many pharmacological research areas, pharmaceutical industry and health-care system.


[Study on compatibility extraction technology of Rhei Radix et Rhizoma, Scutellariae Radix and Phellodendri Chinensis Cortex].
To determine the optimum compatibility extraction technology of Rhei Radix et Rhizoma, Scutellariae Radix and Phellodendri Chinensis Cortex. The drugs were combined respectively firstly, then use HPLC to determinate extraction rates of evaluating indicators including emodin, chrysophano, baicalin and berberine hydrochloride. Orthogonal experiment was used to detect the effect on concentration and volume of ethanol, times of extraction. The extraction rates of evaluating indicators were relatively high in combined extraction of Rhei Radix et Rhizoma with Scutellariae Radix and single extraction of Phellodendri Chinensis Cortex. The optimized combined extraction were 12 times more than the volume of 60% ethanol solution, by boiling for 3 times, each for 1.0 hour, and that of single extraction were 10 times more than the volume of 60% ethanol solution, by boiling for 3 times, each for 1.0 hour. The optimized compatibility extraction technology is reasonable, stable and practical.


Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma.
The immunomodulatory effects of photodynamic therapy (PDT) have been reported in several photosensitizers. Pheophorbide a (Pa), a chlorophyll derivative, shows antitumor effects on a number of human cancers in a PDT approach (Pa-PDT); however, the potential effect of Pa-PDT on the anticancer immunity has never been studied. In the present work, the underlying action mechanism of Pa-PDT was systemically investigated with a human hepatoma cell line HepG2. We found that Pa-PDT significantly inhibited the growth of HepG2 cells with a half maximal inhibitory concentration/endoplasmic reticulum of 0.35 microM at 24 hours by the induction of apoptosis, as shown by externalization of phosphatidylserine, release of mitochondrial cytochrome c, and activation of the caspases cascade in the treated cells. Interestingly, using two-dimensional polyacrylamide gel electrophoresis analysis, a 57-kDa disulfide-isomerase-like ER resident protein (ERp57) that belongs to the HLA class I-restricted antigen-processing machinery was found to be mediated during the Pa-PDT treatment. This activation of antigen presentation was confirmed by Western blot analysis and immunostaining. Furthermore, a cross-presentation of antigen with HLA class I proteins and 70-kDa heat shock protein was found in Pa-PDT-treated cells, as shown by the confocal microscopic observation and immunoprecipitation assay. Nevertheless, the immunogenicity of HepG2 cells was increased by Pa-PDT treatment that triggered phagocytic capture by human macrophages. Our findings provide the first evidence that Pa-PDT can trigger both apoptosis and cancer immunity in the tumor host.


[Neurosciences and philosophy of mind].
In this paper we argue that the interaction between neurosciences and philosophy of the mind is on the way to understand consciousness, and to solve the mind-body or mind-brain problem. Naturalism is the view that mental processes are just brain processes and that consciousness is a natural phenomenon. It is possible to construct a theory about its nature by blending insights from neuroscience, philosophy of the mind, phenomenology, psychology and evolutionary biology.


A study of self-harm in older people: mental disorder, social factors and motives.
Data was collected on seventy-six older people who presented to a specialist self-harm team. Data included: diagnosis, suicide intent, motives for self-harm, social contacts and life events and difficulties. The majority of elderly who harmed themselves had high suicide intent and 69% were depressed. Patients were frequently living alone with an isolated life-style and poor physical health. Depressed self-harm subjects had higher suicide intent scores than non-depressed and to gain relief from an unbearable state of mind was a frequently recorded motive for these patients. Other motives for self-harm appear to be similar between depressed and non-depressed self-harmers. It is important that older people who self-harm receive an appropriate assessment of both risk and need by an experienced mental-health professional skilled at recognising depression in later life. The need for adequate recognition and management of depression in older people in primary care is also highlighted.


31P NMR magnetization-transfer measurements of flux between inorganic phosphate and adenosine 5'-triphosphate in yeast cells genetically modified to overproduce phosphoglycerate kinase.
31P NMR magnetization-transfer measurements were used to measure flux between inorganic phosphate and ATP in the reactions catalyzed by phosphoglycerate kinase and glyceraldehyde-3-phosphate dehydrogenase in anaerobic cells of the yeast Saccharomyces cerevisiae. Flux between ATP and Pi and glucose consumption and ethanol production were measured in cells expressing different levels of phosphoglycerate kinase activity. Overexpression of the enzyme was obtained by transforming the cells with a multicopy plasmid containing the phosphoglycerate kinase coding sequence and portions of the promoter element. Fluxes were also measured in cells in which the glyceraldehyde-3-phosphate dehydrogenase activity had been lowered by limited incubation with iodoacetate. These measurements showed that both enzymes have low flux control coefficients for glycolysis but that phosphoglycerate kinase has a relatively high flux control coefficient for the ATP----Pi exchange catalyzed by the two enzymes. The Pi----ATP exchange velocities observed in the cell were shown to be similar to those displayed by the isolated enzymes in vitro under conditions designed to mimic those in the cell with respect to the enzyme substrate concentrations.


Muscone attenuates susceptibility to ventricular arrhythmia by inhibiting NLRP3 inflammasome activation in rats after myocardial infarction.
Fibrosis and abnormal expression of connexin 43 (Cx43) in the ventricle play vital roles in ventricular arrhythmias (VAs) after myocardial infarction (MI). Muscone, an active monomer of heart-protecting musk pill, has various biological activities, but its effect on susceptibility to VAs in rats with MI has not been determined. In the present study, we investigated the effects of muscone on ventricular inflammation, fibrosis, Cx43 expression, and the occurrence of VAs after MI. An MI model was established by ligating the proximal left anterior descending coronary artery. Then, the MI model rats were administered muscone (2 mg/kg/day) or vehicle (saline)via intragastric injection for 14 days. Cardiac function was evaluated by echocardiography, and an in vivo electrophysiological study was performed on Day 14. Cardiac inflammation, fibrosis, and Cx43 expression were determined by histochemical analysis and western blot analysis. Our results indicated that muscone treatment significantly improved cardiac function and inhibited ventricular inflammation, fibrosis, and nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome activation. Electrocardiogrphy and electrophysiology studies showed that muscone shortened the QRS interval, QT interval, QTc interval, and action potential duration; prolonged the effective refractory period; and reduced susceptibility to VAs in rats after MI. Furthermore, Cx43 expression in the BZ was increased by muscone treatment, and this change was coupled by inhibition of the NLRP3/IL-1β/p38 MAPK pathway. Taken together, our results demonstrated that muscone reduces susceptibility to VA, mainly by decreasing ventricular inflammation and fibrosis, and attenuates abnormal Cx43 expression by inhibiting NLRP3 inflammasome activation after myocardial infarction in rats.


SERS detection of bacteria in water by in situ coating with Ag nanoparticles.
The bio-sensing for the convenient detection of bacteria has been widely explored with the use of various sensing materials and techniques. It is still a challenge to achieve an ultrasensitive and selective, but simple, rapid, and inexpensive detection method for bacteria. We report on surface-enhanced Raman scattering (SERS) for the detection of living bacteria in drinking water by employing a synthesis of silver nanoparticles coating the cell wall of bacteria. We found that the Raman signals intensity of bacteria after AgNP synthesis mainly depends on the zeta potential of the cell wall. The enhancement of the Raman signal of bacteria using this strategy is about 30-fold higher than that in the case of a simply mixed colloid-bacterial suspension. The total assay time required is only 10 min and the total reactants' volume needed to analyze bacteria in a real environment is as low as 1 mL. Particularly, only one droplet of 3 μL sample is necessary for each SERS measurement. Furthermore, we can use this novel strategy to discriminate three strains of Escherichia coli and one strain of Staphylococcus epidermidis by hierarchy cluster analysis. Finally, we can detect bacteria down to 2.5 × 10(2) cells/mL on a hydrophobic glass slide by SERS mapping. Thus, our detection method offers prominent advantages, such as reduced assay time, simple handling, low reactant volumes, small amount of sample, and higher sensitivity and selectivity compared to previously reported label free methods. This novel strategy may be extended to open an avenue for developing various SERS-based biosensors.


Anterior Segment Changes during Accommodation in Accommodative Esotropia.
To evaluate the anterior segment biometric parameters of non-accommodative and accommodative refractive accommodative esotropia (RAE). Eighty-one eyes of 81 patients were included in this prospective, case-control study. The patients were divided into three groups as follows: the RAE group (n = 31), the hypermetropia group (n = 25), and the emmetropia group (n = 25). Measurements were obtained in the non-accommodative (0.0 diopters) and accommodative status (-5.0 diopters) using a Pentacam HR. The anterior chamber depth (ACD), anterior chamber volume (ACV), pupil diameter (PD), and anterior chamber angle (ACA) were evaluated at all four quadrants. The ACD, ACV and PD values in the RAE group were lower than those of the other groups in both states (p < 0.05). The ACD values were lower in the hypermetropia group than in the emmetropia group for the non-accommodative status (p = 0.024) but were similar for the accommodative status (p = 0.225). PD and ACV values were lower in the hypermetropia group than in the emmetropia group in both states (non-accommodative status, p = 0.011 and p = 0.022; accommodative status, p = 0.026 and p = 0.034, respectively). Changes in ACD, ACV and PD during accommodation (Δ) were not significant in the RAE group but were significant for the other groups (hypermetropia: ΔACD, p = 0.001; ΔACV, p = 0.001; ΔPD, p = 0.002; emmetropia: ΔACD, p < 0.001; ΔACV, p = 0.001; ΔPD, p < 0.001). These changes were significantly lower in the hypermetropia group than in the emmetropia group (ΔACD, p = 0.012; ΔACV, p = 0.031; ΔPD, p = 0.034). The anterior chamber in RAE patients was shallower and the increase in convexity of the anterior surface or forward movement of the crystalline lens was more limited during accommodation in RAE.


Microscopic polyangiitis: a rare ANCA-associated small-vessel vasculitis.
Microscopic Polyangiitis (MPA) is an autoimmune disease characterized by pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation. Because many different organ systems may be involved, a wide range of symptoms are possible in MPA. Cutaneous involvement is not frequent. We describe a young girl who presented with multiple vasculitic skin lesions along with arthralgia and after the onset of illness it took 4 years for appropriate diagnosis and management of the disease.


[Evaluation of a breakfast as screening test for the detection of gestational diabetes].
A standard breakfast was evaluated as a screening test (BT) for gestational diabetes in a case-control study. The breakfast had a high carbohydrate content and was designed based on women's preferences in a similar sample. Women were selected with a standard 50 g, 1 hour glucose screening test (GT). Fifteen women had a positive GT and 15 had a negative test. A glucose tolerance test (GTT) and a standard breakfast (719 kcal) were performed to all women. Age, weight, height, tricipital and subscapular skinfold thicknesses were obtained by previously standardized personnel and glucose levels were determined by an automatic technique (oxidase glucose). Ten women had gestational diabetes. Sensitivity and specificity were calculated for the GT and several values of the BT, in order to identify the threshold and optimum time. Concordance of both screening tests with GTT was calculated through Kappa test. For the BT, a sensitivity of 0.90 and specificity of 1.00 with a glucose level > or = 140 mg/L (7.2 mmol/L) at 60 and 90 minutes were found. The 60 minutes timing were preferred due to a shorter waiting time to performed the test. Concordance of GTT with GT and BT was 0.53 and 0.92 respectively, both statistically significant. GT had high frequency of false negative values (6/15) that explain the low kappa value. Standard breakfast can be used as an alternative method for assessing carbohydrate tolerance in pregnancy with a better physiological response in these women.


Case of chromoblastomycosis appearing in an Okinawa patient with a medical history of Hansen's disease.
Chromoblastomycosis is one of several chronic infectious skin diseases caused by various species of dematiaceous fungi. It is clinically characterized by verrucous skin eruptions and occurs most commonly in tropical and subtropical regions. In Okinawa, a subtropical area, there have been only three reported cases of chromoblastomycosis including the present one. Direct microscopic examination of crust specimens and findings of sclerotic cells in histopathology can confirm the diagnosis, and cultures of crust and/or tissue specimens can identify the causative fungi. We herein report the third case of chromoblastomycosis in Okinawa; it arose in an 87-year-old Japanese woman with a history of Hansen's disease, who lived in a leprosarium in Miyako Island. To identify the causative agent as Fonsecaea pedrosoi, we used the polymerase chain reaction and direct sequencing analysis in addition to the usual methods, which include 20% potassium hydroxide microscopy, histopathological confirmation of sclerotic cells by periodic acid-Schiff stain, culture by Sabouraud's glucose agar, slide culture method, and observation of conidia by scanning electron microscopic examination.


2,6-Di-tert-butyl-4-(3-chloro-2-hy-droxy-prop-yl)phenol.
In the title 2-propanol derivative, C(17)H(27)ClO(2), the two tert-butyl groups both have one methyl C atom lying in the plane of the aromatic ring. In the crystal, the phenol group forms a hydrogen bond to the hy-droxy O atom belonging to the alkyl substituent of an adjacent mol-ecule, forming a chain along the ac diagonal. The Cl atom is disordered over two positions in a 0.73 (4):0.27 (4) ratio.


Valproate and neuroprotective effects for bipolar disorder.
Valproate is an anticonvulsant drug but also a mood stabilizer commonly used to treat bipolar disorder. It has a structure of short-chain fatty acid and is becoming a first line treatment for bipolar disorder. The effect mechanism of the vaproate has not been completely established but it has been suggested that alterations in gene expression may be involved in chronic treatment. On the other hand, a growing body of evidence emphasizes that valproate has neuroprotective and neurotrophic actions. Neuroimaging studies that examine neurochemistry in the living brain provide further support for the hypothesis that bipolar disorder is related to changes in neuronal viability and function. In cellular view of point, it was showed that valproate protected rat cerebral cortical and cerebellar granule cells from glutamate-related excitotoxicity, and apoptotic death of the endoplasmic reticulum in C6 glioma cells and PC 12 cells. At the genetic level, growing data suggest that the long-term treatment of mood disorders may involve the regulation of signalling pathways and gene expression in critical neuronal circuits. It has been shown that lithium and valproate produce some changes in basal and stimulated DNA binding to activator protein 1 (AP-1) transcription factors, considering that strategic changes in gene expression in critical neuronal circuits may be important in the treatment of a variety of psychiatric disorders. So, a growing body of evidence establishes its neuroprotective and neurotrophic actions in bipolar disorder.


Preparation of polyhedral oligomeric silsesquioxane based hybrid monoliths by ring-opening polymerization for capillary LC and CEC.
A new organic-inorganic hybrid monolith was prepared by the ring-opening polymerization of octaglycidyldimethylsilyl polyhedral oligomeric silsesquioxane (POSS) with 1,4-butanediamine (BDA) using 1-propanol, 1,4-butanediol, and PEG 10,000 as a porogenic system. Benefiting from the moderate phase separation process, the resulting poly(POSS-co-BDA) hybrid monolith possessed a uniform microstructure and exhibited excellent performance in chromatographic applications. Neutral, acidic, and basic compounds were successfully separated on the hybrid monolith in capillary LC (cLC), and high column efficiencies were achieved in all of the separations. In addition, as the amino groups could generate a strong EOF, the hybrid monolith was also applied in CEC for the separation of neutral and polar compounds, and a satisfactory performance was obtained. These results demonstrate that the poly(POSS-co-BDA) hybrid monolith is a good separation media in chromatographic separations of various types of compounds by both cLC and CEC.


Disruption of oxidative balance in the gut of the western honeybee Apis mellifera exposed to the intracellular parasite Nosema ceranae and to the insecticide fipronil.
The causes underlying the increased mortality of honeybee colonies remain unclear and may involve multiple stressors acting together, including both pathogens and pesticides. Previous studies suggested that infection by the gut parasite Nosema ceranae combined with chronic exposure to sublethal doses of the insecticide fipronil generated an increase in oxidative stress in the midgut of honeybees. To explore the impact of these two stressors on oxidative balance, we experimentally infected bees with N. ceranae and/or chronically exposed to fipronil at low doses for 22 days, and we measured soluble reactive oxygen species (ROS) and ROS damage by quantifying both protein and lipid oxidation in the midgut. Our results revealed a disruption of the oxidative balance, with a decrease in both the amount of ROS and ROS damage in the presence of the parasite alone. However, protein oxidation was significantly increased in the N. ceranae/fipronil combination, revealing an increase in oxidative damage and suggesting higher fipronil toxicity in infected bees. Furthermore, our results highlighted a temporal order in the appearance of oxidation events in the intestinal cells and revealed that all samples tended to undergo protein oxidation during ageing, regardless of treatment.


Antiproliferative effects of methotrexate on peripheral blood mononuclear cells.
Methotrexate was added to cultured mononuclear cells from the peripheral blood of normal individuals and patients with rheumatoid arthritis (RA) to study the drug's effects on mononuclear cell proliferation and antibody synthesis. In the presence of methotrexate, marked antiproliferative effects (to levels less than 15% of baseline) were seen with 3H-deoxyuridine, but not with 3H-thymidine, as the marker of cell division. This difference was not due to altered kinetics of proliferation or the presence of salvage nucleotides in the culture medium. The absence of suppression of antibody production preactivated by pokeweed mitogen in vitro and the low levels of suppression of spontaneous IgM rheumatoid factor production by blood mononuclear cells from RA patients suggested a relative resistance of activated cells to the effects of methotrexate. The effects of methotrexate on both cell proliferation and antibody synthesis were completely reversed by the addition of high concentrations of exogenous folinic acid. The results suggest that methotrexate has effects on immunocompetent cells that may contribute to the efficacy of this drug in the treatment of RA and other autoimmune diseases.


MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells.
During pathologic vessel remodeling, vascular smooth muscle cells (VSMCs) embedded within the collagen-rich matrix of the artery wall mobilize uncharacterized proteolytic systems to infiltrate the subendothelial space and generate neointimal lesions. Although the VSMC-derived serine proteinases, plasminogen activator and plasminogen, the cysteine proteinases, cathepsins L, S, and K, and the matrix metalloproteinases MMP-2 and MMP-9 have each been linked to pathologic matrix-remodeling states in vitro and in vivo, the role that these or other proteinases play in allowing VSMCs to negotiate the three-dimensional (3-D) cross-linked extracellular matrix of the arterial wall remains undefined. Herein, we demonstrate that VSMCs proteolytically remodel and invade collagenous barriers independently of plasmin, cathepsins L, S, or K, MMP-2, or MMP-9. Instead, we identify the membrane-anchored matrix metalloproteinase, MT1-MMP, as the key pericellular collagenolysin that controls the ability of VSMCs to degrade and infiltrate 3-D barriers of interstitial collagen, including the arterial wall. Furthermore, genetic deletion of the proteinase affords mice with a protected status against neointimal hyperplasia and lumen narrowing in vivo. These studies suggest that therapeutic interventions designed to target MT1-MMP could prove beneficial in a range of human vascular disease states associated with the destructive remodeling of the vessel wall extracellular matrix.


[Practice of the use of remote telemedical consultations in "experimental area of work"].
The article presents experimental results of telehealth technology of "medical company--military hospital--central military hospital". Requirements for the equipment, which is used for telehealth consultations and software are specified. Throughout the test were practiced emergency consultations of "physician-physician" interface, including the use of mobile video call and portable terminals of videoconference, remote diagnosis with the use of medical equipment and devices. Data transmission features and video definition are received. The authors determined main types of telecommunication equipment, which are supposed to prospective for the Armed Forces. Prospects of implementation of telecommunication technologies are shown.


Regulatory aspects of N-linked glycoproteins.
Activation of beta-adrenoreceptors in rat parotid acinar cells leads to copious exocrine protein secretion. Additionally, beta-adrenergic stimulation dramatically increases specific secretory protein synthesis and enhances N-linked glycosylation of secretory glycoproteins. Recently, efforts have been directed toward understanding the mechanisms underlying these biosynthetic events. We have been particularly interested in the receptor-mediated regulation of glycosylation. In this report, we evaluate available mechanistic information from the rat parotid gland and present initial data examining the ability of various regulatory agents to modulate N-linked glycosylation in enzymatically-dispersed cell aggregates from surgical specimens of human parotid glands. We conclude that glycosylation of human parotid N-linked glycoproteins may be regulated by extracellular signaling similar to that operative in the rat parotid gland.


Theta-alpha cross-frequency synchronization facilitates working memory control - a modeling study.
Despite decades of research, the neural mechanism of central executive and working memory is still unclear. In this paper, we propose a new neural network model for the real-time control of working memory. The key idea is to consider separately the role of neural activation from that of oscillatory phase. Neural populations encoding different information would not confuse each other when the populations have different oscillatory phases. Depending on the current situation, relevant memories bind together through phase-locking between theta-frequency oscillation of a Central Unit and alpha-frequency oscillations of the relevant group of Memory Units. The Central Unit dynamically controls which Memory Units should be synchronized (and the encoded memory would be processed), and which units should be out of phase (the encoded memory is standby and would not be processed yet). Simulations of two working memory tasks are provided as examples. The model is in agreement with many recent experimental results of human scalp EEG analysis, which reported observations of neural synchronization and cross-frequency coupling during working memory tasks. This model offers a possible explanation of the underlying mechanism for these experiments.


Inactivation of Escherichia coli O157:H7 in packaged ground beef by allyl isothiocyanate.
Commercial allyl isothiocyanate (AIT) was examined for its ability to reduce numbers of Escherichia coli O157:H7 inoculated in fresh ground beef packaged under nitrogen and stored refrigerated or frozen. A five-strain cocktail of E. coli O157:H7 containing 3 or 6 log10 cfu/g was inoculated into 100 g ground beef and formed into 10x1-cm patties. A 10-cm diameter filter paper disk treated with AIT suspended in sterile corn oil was placed on top of a single patty. One patty and paper disk were placed in a bag of Nylon/EVOH/PE with O2 permeability of 2.3 cm3 m(-2) 24 h atm at 23 degrees C. The bags were back-flushed with 100% nitrogen, heat-sealed and stored at 10, 4 and -18 degrees C for 8, 21 or 35 days, respectively. During storage, the AIT levels in the package headspaces were determined by gas liquid chromatography, and mesophilic bacteria and E. coli O157:H7 were counted. The mesophilic aerobic bacteria in ground beef patties were largely unaffected by the addition of AIT. At an initial population of 3 log10 cfu/g, E. coli O157:H7 was reduced by AIT to undetectable levels after 18 days at 4 degrees C or 10 days at -18 degrees C. In samples inoculated with 6 log10 cfu/g, a >3 log10 reduction of E. coli O157:H7 was observed after 21 days at 4 degrees C, while a 1 log10 reduction was observed after 8 and 35 days at 10 and -18 degrees C, respectively. The final AIT concentrations in the headspaces after storage at 10, 4, and -18 degrees C were 444, 456, and 112 microg/ml at 8, 21, and 35 days, respectively. Results showed that AIT can substantially reduce numbers of E. coli O157:H7 in fresh ground beef during refrigerated or frozen storage.


Gastrointestinal disorders next to respiratory infections as leading symptoms of X-linked agammaglobulinemia in children - 34-year experience of a single center.
Respiratory tract infections constitute the most frequent manifestation of X-linked agammaglobulinemia (XLA). There are not many papers elucidating gastrointestinal (GI) disorders, including inflammatory bowel disease (IBD), in such patients. The aim of the study was to evaluate the occurrence of gastrointestinal disorders and IBD compared to respiratory tract infections in XLA individuals. Of 1563 patients with primary immunodeficiencies diagnosed in the Department of Immunology, the Children's Memorial Health Institute (CMHI), 66 boys had a provisional diagnosis of agammaglobulinemia. Forty-four subjects fulfilled definitive ESID (European Society for Immunodeficiencies) diagnostic criteria of XLA. A retrospective analysis of medical history of XLA patients was undertaken. Recurrent respiratory tract infections, particularly bronchitis (73%) and pneumonia (59%), were the most common symptoms of XLA. The GI disorders constituted the next main manifestation (63.6%), followed by upper respiratory tract infections. Twenty-six of 28 XLA patients with GI disorders complained of diarrhea, which was resolved generally after immunoglobulin therapy introduction. Single but prolonged episodes of Campylobacter jejuni diarrhea were reported in two individuals. Inflammatory bowel disease of mild to moderate activity was diagnosed in 1 patient, and local enteritis of mild activity in another one. Gastrointestinal disorders were one of the main manifestations of XLA, reported almost as often as lower respiratory tract infections. The most common GI symptom was diarrhea, which usually resolved after immunoglobulin therapy was started. Infections caused by Giardia lamblia were reported occasionally. Inflammatory bowel disease was diagnosed quite exceptionally, which presumably may be connected with normal T cell immunity.


Effects of feeding fish meal and n-3 fatty acids on ovarian and uterine responses in early lactating dairy cows.
The study was designed to test the effects of dietary supplementation with fish meal or specific n-3 fatty acids on ovarian activity and uterine responses in early lactating cows. From 5 to 50 d in milk (DIM), cows were fed diets that were isonitrogenous, isoenergetic, and isolipidic containing none (control), 1.25, 2.5, or 5% menhaden fish meal (FM) or 2.3% Ca salts of fish oil fatty acids (CaFOFA). Ovarian follicular dynamics were monitored along with plasma concentrations of estradiol and progesterone. Beginning at 23 DIM, cows were induced into a synchronized ovulatory cycle. On d 15 after ovulation (49 DIM), cows were injected with oxytocin and blood samples were collected to monitor uterine release of PGF(2alpha) (measured as 13, 14-dihydro-15-keto PGF(2alpha); PGFM). Uterine endometrial biopsies were collected for fatty acid analysis and cyclooxygenase-2 (COX-2) protein measurement. Ovarian follicular activities as well as plasma estradiol and progesterone concentrations were similar across diets. Endometrial fatty acid composition of eicosapentaenoic acid (C20:5, n-3) and docosahexaenoic acid (C22:6, n-3) were increased as much as 3-fold by supplementation with fish meal and CaFOFA. Conjugated linoleic acid (C18:2 cis-9, trans-11) in the endometrium was also increased; conversely, arachidonic acid (C20:4, n-6) percentage was decreased by 5% FM. Plasma PGFM response to oxytocin injection was not different among diets and endometrial COX-2 protein abundance did not differ. Results from this experiment demonstrate that dietary supplementation with fish meal or n-3 fatty acids in early lactating dairy cows significantly increased uterine n-3 fatty acid concentrations, but had no apparent effect on endometrial COX-2 or PGF(2alpha) production in response to oxytocin challenge.


[Reliability and validity of the Japanese translation of Brief Self-Control Scale (BSCS-J)].
Self-control refers to the ability to execute goal-oriented behavior despite the presence of temptation(s) to do otherwise. Since self-control has a wide-range impact on our daily lives, it is of critical importance to assess individual differences of self-control with a highly reliable and valid, yet simple, measure. Toward this end, three studies were conducted to test reliability and validity of the Japanese-translated version of Brief Self-Control Scale (Tangney, Baumeister, & Boone, 2004). The scale showed good internal consistency (Study 1) and retest reliability (Study 2). The. total score of the scale was correlated with the self-reported indices of self-control (e.g., daily experience of ego-depletion, study hours) and performance in the Stop Signal Task (Study 3), indicating its high converging validity.


Leucocytoclastic vasculitis as a late complication of clopidogrel therapy.
We describe a case of leucocytoclastic vasculitis manifested as exanthematous rash in a 57-year-old woman on long-term therapy with clopidogrel. The diagnosis was confirmed by skin biopsy. The patient was managed symptomatically with oral antihistaminics and topical steroids in consultation with dermatologists. Clopidogrel therapy was discontinued on suspicion of drug-induced vasculitis. The rash resolved completely within 2 weeks of withdrawal of clopidogrel, satisfying criteria for a probable adverse drug reaction. Leucocytoclastic vasculitis is an unusual adverse effect of clopidogrel therapy and even rarer as a late complication.


Mapping Residency Global Health Experiences to the ACGME Family Medicine Milestones.
Global health (GH) experiences are a unique part of family medicine (FM) training that offer an opportunity for residents to demonstrate development across a multitude of the milestones recently implemented by the Accreditation Council for Graduate Medical Education (ACGME). The GH experience presents an opportunity for resident development, and including a component of written reflection can provide tangible evidence of development in areas that can be difficult to assess. A mixed methods approach was used to integrate quantitative (frequency) data with qualitative content from the written reflections of 12 of our FM residents who participated in GH experiences. Written reflections touched on each of the 22 milestones, although some milestones were noted more frequently than others. The most commonly identified milestones fell within the competency areas of systems-based practice, professionalism, and practice-based learning and improvement. Our qualitative approach allowed us to gain an appreciation of the unique experiences that demonstrated growth across the various milestones. We conclude that any program that offers GH experiences should incorporate some form of written reflection to maximize resident growth and offer evaluative faculty a window into that development.


Predictor of gram-negative bacteremia in cirrhotic patients with skin and soft-tissue infections.
Cirrhosis always goes with profound immunity compromise, and makes those patients easily be the target of skin and soft-tissue infections (SSTIs). Cirrhotic patients with SSTIs have a dramatically increased mortality. To recognize the risk factors of gram-negative infections are critical for improving survival rate. A retrospective cohort study of hospitalized cirrhotic patients with SSTIs and gram-negative bacteremia (GNB) was conducted in 2 tertiary hospitals in southern Taiwan between March 2015 and January 2020. Another group were matched by controls with non-GNB based on time, demographics and immune status. Data such as infectious location, comorbidities, and laboratory findings were recorded and compared. Receiver operating curve and the area under the curve were used to evaluate its discriminating ability. A total of 186 patients were included, 62 in GNB group and 124 in non-GNB group. Comorbidities that were significant risk factors for gram-negative bacteremia included acute kidney injury. Significant risk factors evident in laboratory evaluations included higher model for end-stage liver disease score, higher serum lactate, higher C-reactive protein and higher creatinine level. This study found acute kidney injury, or those exhibiting hyperlactatemia (>16 mg/dL), high MELD score (>14), high CRP (>50 mg/dL), and high creatinine (>2.0 mg/dL) were risk factors associated with gram-negative bacteremia. Cirrhotic patients with SSTIs with aforementioned risk factors should pay more attention by clinicians due to higher mortality.


A Smart Image Encryption Technology via Applying Personal Information and Speaker-Verification System.
In this paper, a framework for authorization and personal image protection that applies user accounts, passwords, and personal I-vectors as the keys for ciphering the image content was developed and connected. There were two main systems in this framework. The first involved a speaker verification system, wherein the user entered their account information and password to log into the system and provided a short voice sample for identification, and then the algorithm transferred the user's voice (biometric) features, along with their account and password details, to a second image encryption system. For the image encryption process, the account name and password presented by the user were applied to produce the initial conditions for hyper-chaotic systems to generate private keys for image-shuffling and ciphering. In the final stage, the biometric features were also applied to protect the content of the image, so the encryption technology would be more robust. The final results of the encryption system were acceptable, as a lower correlation was obtained in the cipher images. The voice database we applied was the Pitch Tracking Database from the Graz University of Technology (PTDB-TUG), which provided the microphone and laryngoscope signals of 20 native English speakers. For image processing, four standard testing images from the University of Southern California-Signal and Image Processing Institute (USC-SIPI), including Lena, F-16, Mandrill, and Peppers, were presented to further demonstrate the effectiveness and efficiency of the smart image encryption algorithm.


Abnormal erythroid maturation leads to microcytic anemia in the TSAP6/Steap3 null mouse model.
Genetic ablation of the ferrireductase STEAP3, also known as TSAP6, leads to severe microcytic and hypochromic red cells with moderate anemia in the mouse. However, the mechanism leading to anemia is poorly understood. Previous results indicate that TSAP6/Steap3 is a regulator of exosome secretion. Using TSAP6/Steap3 knockout mice, we first undertook a comprehensive hematologic characterization of the red cell compartment, and confirmed a dramatic decrease in the volume and hemoglobin content of these erythrocytes. We observed marked anisocytosis as well as the presence of fragmenting erythrocytes. Consistent with these observations, we found by ektacytometry decreased membrane mechanical stability of knockout red cells. However, we were unable to document significant changes in the expression levels of the major skeletal and transmembrane proteins to account for this decrease in the membrane stability. Furthermore, there were no differences in red cell survival between wild type and knockout animals. However, when we monitored erythropoiesis, we found a decreased number of proerythroblasts in the bone marrow of TSAP6/Steap3(-/-) animals. In addition, progression from the proerythroblastic to the orthochromatic stage was affected, with accumulation of cells at the polychromatic stage. Altogether, our findings demonstrate that abnormal erythroid maturation is the main cause of anemia in these mice.


Quaternary arsenides AM(1.5)Tt(0.5)As2 (A = Na, K, Rb; M = Zn, Cd; Tt = Si, Ge, Sn): size effects in CaAl2Si2- and ThCr2Si2-type structures.
Ten quaternary arsenides AM(1.5)Tt(0.5)As2 (A = Na, K, Rb; M = Zn, Cd; Tt = Si, Ge, Sn) have been prepared by stoichiometric reactions of the elements at 600-650 °C. Seven of them (NaZn(1.5)Si(0.5)As2, NaZn(1.5)Ge(0.5)As2, NaZn(1.5)Sn(0.5)As2, NaCd(1.5)Sn(0.5)As2, KZn(1.5)Sn(0.5)As2, KCd(1.5)Sn(0.5)As2, RbCd(1.5)Sn(0.5)As2) adopt the trigonal CaAl2Si2-type structure (Pearson symbol hP5, space group P3m1, Z = 1, a = 4.0662(3)-4.4263(7) Å, c = 7.4120(5)-8.4586(14) Å), whereas the remaining three (KZn(1.5)Si(0.5)As2, KZn(1.5)Ge(0.5)As2, RbZn(1.5)Ge(0.5)As2) adopt the tetragonal ThCr2Si2-type structure (Pearson symbol tI10, space group I4/mmm, Z = 2, a = 4.0613(10)-4.1157(5) Å, c = 14.258(3)-14.662(2) Å). Both structure types contain anionic [M(1.5)Tt(0.5)As2] slabs that are built from edge-sharing tetrahedra and that stack alternately with nets of A cations. A structure map delineates the formation of these structure types for AM(1.5)Tt(0.5)As2 as a function of simple radius ratios. Although these arsenides have charge-balanced formulations, band structure calculations on NaZn(1.5)Tt(0.5)As2 (Tt = Si, Ge, Sn) indicate that semimetallic behavior is predicted as a result of overlap of the valence and conduction bands.


Candida fermentati: a rare yeast involved in fungal keratitis.
The aim of this study was to report a rare case of fungal keratitis from Eastern India. This is a case report. A 52-year-old man with a history of minor trauma presented with a total corneal ulcer and hypopyon in the left eye. Microbiologic examination of corneal scrapings showed yeast cells in direct smear and typical yeast colonies on multiple solid agar media. Identification of the organism isolated in the culture was performed using the D1/D2 region of the large subunit (LSU 28S rDNA)-based molecular technique. Polymerase chain reaction amplified a band with a sequence that was 100% homologous with that of Candida fermentati. The organism was susceptible to amphotericin B and anidulafungin and demonstrated resistance to voriconazole, itraconazole, and fluconazole. Therapeutic keratoplasty was performed, followed by the recurrence of the infection in the graft, which was controlled with topical and intracameral amphotericin B. At the end of 3 months, the affected eye had developed phthisis bulbi. This is the first report of isolation of C. fermentati, a species closely related to Candida guilliermondii, from keratitis. Molecular diagnostic techniques are helpful in the accurate identification of this organism, which is clinically important in view of an antifungal susceptibility pattern that differs from that of other yeasts and for selection of appropriate therapy.


Evaluation of whole-mount in situ hybridization as a tool for pathway-based toxicological research with early-life stage fathead minnows.
Early-life stage fish can be more sensitive to toxicants than adults, so delineating mechanisms of perturbation of biological pathways by chemicals during this life stage is crucial. Whole-mount in situ hybridization (WISH) paired with quantitative real-time polymerase chain reaction (QPCR) assays can enhance pathway-based analyses through determination of specific tissues where changes in gene expression are occurring. While WISH has frequently been used in zebrafish (Danio rerio), this technology has not previously been applied to fathead minnows (Pimephales promelas), another well-established small fish model species. The objective of the present study was to adapt WISH to fathead minnow embryos and larvae, and use the approach to evaluate the effects of estrone, an environmentally-relevant estrogen receptor (ER) agonist. Embryos were exposed via the water to 0, 18 or 1800 ng estrone/L (0, 0.067 and 6.7nM) for 3 or 6 days in a solvent-free, flow-through test system. Relative transcript abundance of three estrogen-responsive genes, estrogen receptor-α (esr1), cytochrome P450-aromatase B (cyp19b), and vitellogenin (vtg) was examined in pooled whole embryos using QPCR, and the spatial distribution of up-regulated gene transcripts was examined in individual fish using WISH. After 3 days of exposure to 1800 ng estrone/L, esr1 and cyp19b were significantly up-regulated, while vtg mRNA expression was not affected. After 6 days of exposure to 1800 ng estrone/L, transcripts for all three genes were significantly up-regulated. Corresponding WISH assays revealed spatial distribution of esr1 and vtg in the liver region, an observation consistent with activation of the hepatic ER. This study clearly demonstrates the potential utility of WISH, in conjunction with QPCR, to examine the mechanistic basis of the effects of toxicants on early-life stage fathead minnows.


Polymorphisms of MTHFR and TYMS predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer.
Breast cancer is a global problem, and a large number of new cases are diagnosed every year. Capecitabine is effective in patients with metastatic breast cancer (MBC). Hand-foot syndrome (HFS) is a common adverse effect of capecitabine. In this study, we investigated the association between single nucleotide polymorphisms (SNPs) in genes involved in capecitabine metabolism pathways and capecitabine-induced HFS in Chinese patients with MBC to identify some predictive genetic biomarkers. We selected 3 genes involved in capecitabine metabolism and screened genetic variants in these target genes. We genotyped a total of 22 SNPs in the thymidylate synthase gene (TYMS), the methylene tetrahydrofolate reductase gene (MTHFR), and the ribonucleotide reductase M1 gene (RRM1) in 342 MBC patients treated with capecitabine-based chemotherapy. The genotype distributions of each SNP in patients with and without HFS were assessed using Pearson's χ2 test, and the relationship between HFS and genotypes of SNPs was determined using logistic regression analysis. The association between SNPs and their corresponding gene expression was analyzed using the Blood expression quantitative trait loci (eQTL) browser online tools. We found 4 positive sites for HFS in the TYMS and MTHFR genes: TYMS rs2606241 (P = 0.022), TYMS rs2853741 (P = 0.019), MTHFR rs3737964 (P = 0.029), and MTHFR rs4846048 (P = 0.030). Logistic regression analyses showed that the genotype AG of MTHFR rs3737964 [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.31-0.97, P = 0.038] and MTHFR rs4846048 (OR = 0.54, 95% CI 0.30-0.98, P = 0.042) were protective factors of HFS, whereas the genotype CT of TYMS rs2853741 (OR = 2.25, 95% CI 1.31-3.87, P = 0.012) increased the risk of HFS. The association between the genotype GT of TYMS rs2606241 (OR = 1.27, 95% CI 0.73-2.23, P = 0.012) and HFS was uncertain. Further eQTL analyses confirmed that the alleles of rs3737964 and rs4846048 affected the gene expression levels of MTHFR in cis. We have identified four potentially useful pharmacogenetic markers, TYMS rs2606241, TYMS rs2853741, MTHFR rs3737964, and MTHFR rs4846048 to predict capecitabine-induced HFS in MBC patients.


NOX2-dependent immunosuppression in chronic myelomonocytic leukemia.
Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8+ T effector memory cells, and CD8+ T effector cells. Inhibitors of ROS formation and scavengers of extracellular ROS prevented CMML cell-induced lymphocyte death and facilitated NK cell degranulation toward Ab-coated, primary CMML cells. In patients with CMML, elevation of immature cell counts (CD34+) in blood was associated with reduced expression of several NK cell-activating receptors. We propose that CMML cells may use extracellular ROS as a targetable mechanism of immune escape.


Shockwave Therapy for Erectile Dysfunction: Which Gives the Best Results? A Retrospective National, Multi-Institutional Comparative Study of Different Shockwave Technologies.
Low-intensity shockwave therapy (Li-SWT) is a promising option for the treatment of erectile dysfunction (ED). Many devices with different characteristics in terms of generators, shockwaves, set-up parameters and procedure protocols are commercially available. In this report, we present our experience with the main shockwave technologies currently in use in clinical practice for ED treatment. A retrospective national, multi-institutional study was performed to compare the effects of different shockwave technologies in ED patients. All of the subjects underwent 8 consecutive weekly physical treatments with SWT under either a focused or non-focused regimen: 3,000 shocks per session at 0.09 mJ/mm2 and 10,000 shocks per session at 15 Hz and 90 mJ, respectively. Efficacy was evaluated by comparing pre- and post-treatment Sexual Health Inventory in Men (SHIM) scores, International Index of Erectile Function (IIEF-5) and Erection Hardness Score (EHS). Possible relationships between type of shockwave generator, source, morphology and type of ED were investigated. A total of 94 men were included in the analysis. There were no significant differences in the baseline clinical characteristics or demographics. The mean (SD) increase in the scores from questionnaires evaluated at 8 weeks was clinically and statistically significant, with overall improvements of +5.49, +5.47 and +1.18 (p<0.0001) in the IIEF-5, SHIM, and EHS scores, respectively. The increases in these scores were evaluated by a multiple regression analysis, in relation to the shockwave generator, type of ED, shockwave source and morphology, but none of the factors examined predicted improvement. No side effects were reported with any device. SWT is a clinically effective and safe treatment for ED that is independent of the generator type, source, shockwave morphology emitted, type of ED and perhaps treatment protocol.


Getting dengue from vector mosquito bite at home: a reappraisal on chance based on molecular epidemiology data in Indochina.
Dengue is an important vector borne viral infection. At present, it is endemic in many tropical countries. A molecular epidemiology of viral type in patients and mosquitoes can give useful epidemiology data for disease control. In Indochina, dengue is very common and the molecular epidemiology surveillance is continuously performed. Here, the authors reappraise on available local data from epidemiology studies of viral type in patients and mosquitoes in an endemic area of dengue in Indochina. According to analysis, the authors found that a considerable number of dengue patients do not have the same viral type with caught mosquito vector at their home. According to this study, a chance that a dengue patient gets pathogen from mosquito bite at home is 2.185%. The chance of getting dengue from the vector mosquito bite at home is not high. Hence, a public health policy to control of mosquito vector at home has to extend to universal control at any public places.


Dynamic Touch as Common Ground for Enactivism and Ecological Psychology.
The main purpose of this article is to show that enactivism and ecological psychology share more aspects than is often recognized. Rather than debating about differences, commonalities between the approaches are illustrated with the example of dynamic touch. Dynamic touch is a form of touch that implies muscles and tendons and that allows the perception of hand-held objects that are wielded but not seen. Given that perceivers perform the wielding movements with effort, dynamic touch necessarily implies active exploration. The strength of dynamic touch as an example lies in the fact that it has been formalized and analyzed in detail at the level of the laws that govern the organism-environment system. The example provides empirically supported instantiations of sensorimotor contingencies, in enactivist terms, and of intentional exploration and information detection, in ecological terms. Moreover, dynamic touch is a practical example of the enactivist concepts of bringing-forth the world and sense-making. As a second purpose, we use the example of dynamic touch to clarify key concepts of the ecological approach. Specifically, we analyze the concepts of invariance and affordance, indicating the crucial difference between perceiving and actualizing affordances, and highlighting the importance of these concepts for the dialogue between enactivism and ecological psychology.


Vital pulp treatment for traumatized permanent teeth: A systematic review.
Traumatic dental injuries involving the pulp are quite common and there is a need to evaluate the quality of evidence on the success of vital pulp treatment (VPT) interventions in traumatised permanent teeth. The aim of this systematic review was to assess the success of VPT in the management of traumatised human vital permanent teeth diagnosed with complicated crown or crown-root fractures. An electronic search of the following databases: Web of Science, Scopus, PubMed, MEDLINE, EMBASE, LILACS, Clinical Trial Registries and the grey literature was performed until 25th /8/2021. Controlled clinical trials, cohort studies, case-control studies, case series with at least five cases and a minimum of 12-months follow-up were included. Non-English language literature was excluded. Two independent assessors performed study selection, data extraction and quality assessment using the National Institutes of Health's quality assessment tool. Disagreements were resolved through consensus/with a third assessor. A total of 14-studies (2-controlled clinical trials, 1-case-control, and 11-case series) published between 1978-2020, with a total of 1081 permanent teeth and an age range between 6-42 years-old were included. Bias analysis ranged considerably from 'good' to 'poor'. Meta-analysis was not performed due to data heterogeneity, unclear reporting, and limited number of controlled clinical studies. Partial pulpotomy was the main reported clinical procedure with an overall success rate between 82.9-100%. Complete pulpotomy and direct pulp capping were associated with lower success rates of 79.4-85.7% and 19.5%, respectively. Calcium hydroxide was the main pulp capping material with favourable clinical and radiographic success (79.4-100%). Biodentine® , mineral trioxide aggregate and IRoot® BP were also associated with a high clinical and radiographic success, 80-91%, 80-100%, and 90-100%, respectively, albeit in fewer studies. Although a high success rate has been reported when using VPT in managing pulpally involved traumatised teeth, the results of this systematic review clearly highlighted a paucity and low quality of the available evidence. Overall high success of VPT in the management of traumatised vital permanent teeth were reported, although based on limited evidence of well-conducted clinical studies. PROSPERO database (CRD42020205213).


Trends in Systemic Antibiotic Therapy of Endodontic Infections: a Survey among Dental Practitioners in Lithuania.
Prescription trends to certain antibiotic classes in Lithuania have been observed. Considering the potential contribution to antimicrobial resistance and the evidence of inappropriate prescriptions highlights, the periodical assessment of antibiotic consumption trends is required. The aim of this study was to assess prescription behaviours of Lithuanian general dental practitioners concerning the systemic antibiotic therapy of endodontic infections. A sample of 198 Lithuanian dentists, registered on the database of the Lithuanian Dental Chamber, provided anonymous information about their clinical work by means of an online questionnaire. Among the participants, antibiotics were prescribed in less than 20% of endodontic cases. Most common diagnosis for the prescription was symptomatic apical periodontitis with periostitis (90%) and apical abscesses with systemic involvement (54%). Amoxicillin and co-amoxiclav were the preferred choices for the antimicrobial therapy. The preference of clavulanic acid combination over simple usage of amoxicillin is increasing relative to the participants age (P = 0.016) and working experience (P = 0.008). Clindamycin is prescribed in cases of allergy to beta-lactams. Practitioners with less years of clinical activity were more likely to prescribe antibiotics for spreading infections, than their associates with more than 10 years of practice (P < 0.001). Clinicians of higher age were found to be more likely to prescribe broad-spectrum antibiotic combinations compared to their younger associates. The majority of practitioners were aware of the clinical recommendations.


Cardiac valve replacement in patients over 75 years of age.
Elderly patients with symptomatic cardiac valvular malfunction have a grave prognosis if managed medically but can be offered a reasonable chance for long-term survival and a good chance for improvement by replacement of the malfunctioning valve. A series of patients 75 years of age and older who underwent aortic valve replacement (31 patients) mitral valve replacement (9 patients), or combined valve replacement (on patient) has been reviewed. The overall operative mortality for aortic valve replacement was 23% (17% over the past 5 years) and the 5-year actuarial survival was 54 +/- 11%. The operative mortality for mitral replacement was 11% and the 5-year actuarial survival was 55 +/- 21%. The average hospital stay for survivors was 19 days after aortic valve replacement. Four patients have had embolic events since valve replacement, 3 after aortic and one after mitral valve replacement. The addition of coronary artery bypass surgery to the valve replacement procedure is becoming more frequent and may have contributed to improved operative survival. A literature review of reported clinical experience shows that the advancement of cardiac surgery has permitted a redefining of the group thought as "elderly", and that this group has an improved operative survival with the improvements in cardiac valve surgery.


Changes in employer-sponsored private health insurance among retirees in Ontario: a cross-sectional study.
Employer-sponsored health insurance, particularly for retirees with limited incomes, plays a major funding role in Canadian health care, including prescription drugs and dental services. We aimed to investigate the changes in retiree health insurance availability over time. We performed a secondary analysis of data from the 2005 and 2013-2014 cycles of the Canadian Community Health Survey using multivariate logistic regression to study changes in retiree coverage availability over time in Ontario. We estimated the adjusted odds ratios of having employer coverage for likely retirees (people over age 65 yr who reported not working and those over age 75 yr), adjusting for a number of potential confounders. Sensitivity analysis was also performed for coverage of different treatments separately. The response rate was 76% for the 2005 cycle and 66% for 2013-2014 for the entire survey. The characteristics of respondents in the 2 survey cycles were similar, except respondents in 2013-2014 were wealthier. In our adjusted model, respondents in 2013-2014 had lower odds of reporting retiree coverage than respondents in 2005 (adjusted odds ratio 0.87; 95% confidence interval 0.77-0.99). This represents an absolute reduction in the probability of receiving retiree coverage of up to 3.4%. Our analysis suggests that the rate of retiree health insurance has declined for Canadians with similar characteristics over the past decade. As we know insurance coverage has a strong association with use of treatments such as prescription drugs and dental care, this decline may result in decreased access to treatment and is an issue that warrants further investigation.


Effect of different periods of calcium hydroxide dressing on the fracture resistance of root dentin.
The aim of this in vitro study was to evaluate the effect of different periods of intracanal calcium hydroxide (Ca[OH]2) dressing application on the compressive strength of root dentin. The roots of 80 human mandibular premolars were prepared via the crown-down technique and randomly distributed into 1 control group (Gc) and 4 experimental groups (n = 16). The experimental groups were based on the length of intracanal Ca(OH)2 dressing use: 7 (G7d), 14 (G14d), 30 (G30d), or 90 (G90d) days. The prepared roots in the control group were left unfilled. The root canals in the experimental groups were dried, filled with the Ca(OH)2 dressing, and radiographed, and then the root canal entrance was sealed. All of the specimens were stored in saline solution at 37°C for the duration of their experimental period. After storage, the roots were sectioned with 2 cuts. The first cut was 1 mm below the cementoenamel junction, and the second was 6 mm apical to the first cut, creating 6-mm-long × 3-mm-diameter cylinders. At each test period, 4 specimens from Gc and all 16 specimens from the appropriate experimental group were submitted to compressive strength testing (1 mm/min). The groups demonstrated the following mean (SD) values of compressive strength: Gc, 174.41 (56.10) MPa; G7d, 161.29 (39.10) MPa; G14d, 130.27 (57.53) MPa; G30d, 167.88 (34.24) MPa; and G90d, 129.62 (31.46) MPa. Statistically significant differences among the groups were found (P = 0.007; analysis of variance and Tukey test, α = 5%), with a significant difference between Gc and both G14d and G90d (P < 0.05). There were no statistically significant differences (P > 0.05) among the mean compressive strength values of the experimental groups (7, 14, 30, and 90 days). The results indicated that the use of Ca(OH)2 as an intracanal medication for periods of 14 and 90 days reduced the fracture resistance of root dentin.


Pituitary-thyroid axis development during the larval-juvenile transition in the pejerrey Odontesthes bonariensis.
The morphological development of the thyroid gland of pejerrey Odontesthes bonariensis during larval-juvenile transition was studied and related to whole-body concentrations of thyroxine (T4 ) and tri-iodothyronine (T3 ). A complementary (c)DNA fragment of the thyroid-stimulating hormone β-subunit (tshb) was sequenced and transcript levels quantified during this period. Follicles with eosinophilic and T4 -immunoreactive colloids were detected at hatching together with tshb transcript levels and whole-body concentrations of T4 and T3 hormones. Thyroid follicles were located in the subpharyngeal region associated with the ventral aorta below the hyoid bone. Follicle structure switched from the rounded form at hatching to oval in juveniles. Significant increase of follicle number per larva, mean colloidal area and total colloidal area was observed throughout development with maximum values at the end of the larval-juvenile transition. A significant decrease of tshb expression together with a significant increase in T4 and T3 whole-body concentrations was observed prior to achieving the juvenile phenotype. These results are in accordance with a negative feedback regulation of tshb expression by thyroid hormones and a possible association between thyroid hormone levels and the acceleration of metabolic processes necessary to complete metamorphosis.


Distribution of HPV genotypes in 282 women with cervical lesions: evidence for three categories of intraepithelial lesions based on morphology and HPV type.
Previously we found differences in the distribution of the individual human papillomavirus types in cervical cancers and high-grade squamous intraepithelial lesions. This suggested that there were differences in risk for progression of high-grade squamous intraepithelial lesions that were related to human papillomavirus type within the category of oncogenic genotypes. In this work, we add additional cases including low-grade squamous intraepithelial lesions. ThinPrep samples from 282 squamous intraepithelial lesions and invasive cervical cancers were categorized morphologically by consensus interpretation and genotyped for 27 individual human papillomavirus types by polymerase chain reaction-based reverse line blot analysis using PGMY09/PGMY11 consensus primers for the L1 open reading frame. The 27 human papillomavirus types were divided into three categories: high risk 16, 18, 31, 45; intermediate risk 33, 35, 39, 51, 52, 56, 58, 59, 68, 73, 82, 83; and low risk: 6, 11, 26, 40, 42, 53, 54, 55, 57, 66, and 84. Of the 282 cases of cancer and squamous intraepithelial lesions, 95.7% were positive for one or more of 27 human papillomavirus types and 38.7% had two or more genotypes. Three major categories of squamous intraepithelial lesions were identified based upon the combination of consensus diagnosis and human papillomavirus category: (1) high-grade squamous intraepithelial lesions associated with high-risk human papillomavirus types that appear to be at increased risk for progression to carcinoma; (2) squamous intraepithelial lesions (typically low-grade intraepithelial lesions and high-grade lesions consistent with moderate dysplasia) associated with intermediate risk human papillomavirus types with limited or indeterminate risk for progression; (3) low-grade squamous intraepithelial lesions associated with low-risk human papillomavirus types with little or no risk for progression. Only a subset of human papillomavirus genotypes commonly considered to be oncogenic were closely associated with invasive cervical cancer and high-grade squamous intraepithelial lesions classed as severe dysplasia. Other oncogenic types were closely associated with high-grade squamous intraepithelial lesions of moderate dysplasia and low-grade squamous intraepithelial lesions. This suggests that risk for progression to invasion in squamous intraepithelial lesions is closely related to human papillomavirus genotype. Knowledge of the associated human papillomavirus type in women with morphologic squamous intraepithelial lesions may help to clarify risk for progression.


Multivariate methods for the analysis of complex and big data in forensic sciences. Application to age estimation in living persons.
Researchers handle increasingly higher dimensional datasets, with many variables to explore. Such datasets pose several problems, since they are difficult to handle and present unexpected features. As dimensionality increases, classical statistical analysis becomes inoperative. Variables can present redundancy, and the reduction of dataset dimensionality to its lowest possible value is often needed. Principal components analysis (PCA) has proven useful to reduce dimensionality but present several shortcomings. As others, forensic sciences will face the issues specific related to an evergrowing quantity of data to be integrated. Age estimation in living persons, an unsolved problem so far, could benefit from the integration of various sources of data, e.g., clinical, dental and radiological data. We present here novel multivariate techniques (nonlinear dimensionality reduction techniques, NLDR), applied to a theoretical example. Results were compared to those of PCA. NLDR techniques were then applied to clinical, dental and radiological data (13 variables) used for age estimation. The correlation dimension of these data was estimated. NLDR techniques outperformed PCA results. They showed that two living persons sharing similar characteristics may present rather different estimated ages. Moreover, data presented a very high informational redundancy, i.e., a correlation dimension of 2. NLDR techniques should be used with or preferred to PCA techniques to analyze complex and big data. Data routinely used for age estimation may not be considered suitable for this purpose. How integrating other data or approaches could improve age estimation in living persons is still uncertain.


[Molecular diagnostics of ovarian cancer using proteome techniques].
Ovarian cancer is most common gynecological malignancy which is difficult for early diagnostics. Development of new methods for diagnostics of ovarian cancer, especially, on early stage, is the urgent problem of modern oncology. A general approach to early diagnostics of cancer is a discovery of specific blood disease biomarkers. Ovarian cancer biomarker used in the modern art, CA125, has some drawbacks resulting in extensive research recently directed to this tumor diagnosis. In particular, it was shown the advantage of parallel use of several diagnostic biomarkers instead of the single one. Proteome techniques (two-dimensional electrophoresis, mass-spectrometry methods) in connection to bioinformatics represent a powerful tool for new biomarker discovery. In this respect, the best method of choice is shown to be SELDI-TOF (Surface-enhanced laser desorption/ionization time-of-flight) technique which combines chromatography protein chip application and mass-spectrometry-based detection. In this review, new ovarian biomarker data obtained by proteome methods are summarized.


Association of pseudothrombocytopenia and pseudoleukopenia: evidence for different pathogenic mechanisms.
A case of spurious automated leukocyte and platelet counts due to EDTA-dependent platelet-neutrophil agglutination is described. Whole blood anticoagulated with K3EDTA, sodium citrate and lithium heparin was analysed at short time intervals up to 6 h from sampling at 37 degrees C and at room temperature (RT = 27 degrees C). A phenomenon of platelet clumping occurred at both temperatures with all the anticoagulants (pseudothrombocytopenia), while platelet-granulocyte agglutination was present only with EDTA at RT. Aggregates consisting of up to 80 neutrophils were seen on the blood smear. The contemporary presence of platelet clumping caused a reduction of WBC count of only 25% the initial, while leukocyte differential was markedly altered (pseudolymphocytosis). Further experiments were performed mixing plasma and serum of the patient with packed cells (PC) from a normal donor in the presence of different anticoagulants and at various dilutions and temperatures. Platelet-neutrophil agglutination occurred only in the presence of EDTA at temperatures lower than 37 degrees C, and was abolished by plasma dilutions from 1:8 onwards. Similarly, it was inhibited by incubation with dithiothreitol (DTT), in contrast with platelet clumping. The latter phenomenon was triggered by an EDTA concentration lower than that necessary to cause platelet-neutrophil agglutination (0.5 mg ml-1 vs. 0.77 mg ml-1). Obtained results suggest the causal association of 2 different phenomena, both transferable to normal cells by means of patient plasma and serum. In the article the pathogenetic implications of the case are discussed.


CRISPR Guide RNA Library Screens in Human Induced Pluripotent Stem Cells.
High-throughput CRISPR guide RNA (gRNA) library screen, that is, CRISPR/Cas9 screen, enables the unbiased identification of gene functions in a variety of biological processes. Typical pooled CRISPR/Cas9 screen couples a gRNA library and a guided Cas9 or dCas9 endonuclease to target specific gene loci, and then systematically uncover the causal link between candidate genes and observed cellular phenotypes via gRNA depletion or enrichment in screens. Here, we describe a detailed method of puromycin (PURO) concentration titration and lentiviral CRISPR gRNA library titration in Cas9 expressing monoclonal human iPSC line (Cas9+MNhiPSC) prior to performing the screens, conducting pooled CRISPR gRNA library screens in Cas9+MNhiPSC, genomic DNA extraction from the selected cell subpopulation and sequencing library preparation as well as next generation sequencing (NGS) to generate gRNA read counts. In CRISPR/Cas9 screen, we aim for 30% transduction efficiency (i.e., multiplicity of infection = 0.3) to ensure most of infected cells receive only one gRNA. The principles in this method can be applied to CRISPR perturbation (knockout, activation, repression or base editing) screens with other CRISPR gRNA libraries across many other cell models and other species.


A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia.
Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700-1500 h; P = .002), and afternoon (1500-2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700-1500 h; P = .02) 17-OHP AUC. Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH.


Smoking and occlusive peripheral arterial disease. Clinical review.
Cigarette smoking is a strong but avoidable risk factor for development of cardiovascular disease and its acute complications. Intermittent claudication is most strikingly associated with smoking. The link between smoking and occlusive peripheral arterial disease is dose-dependent and can be broken by cessation of smoking. The risk of chronic as well as acute limb ischemia is then decreased in conservatively treated patients and also in those with reconstructive arterial surgery. Heavy smoking seems to abolish the positive effect of adjuvant antiplatelet medication. Cessation of smoking is a cornerstone in the management of occlusive peripheral arterial disease at any stage.


Effect of changing indications and techniques on total hip resurfacing.
Recently, improved metal-on-metal bearing technology has led to the reemergence of resurfacing as a reasonable option for total hip arthroplasty. During the course of a prospective multicenter FDA-IDE evaluation of metal-on-metal total hip resurfacings, we modified our indications and emphasized surgical technique where the femoral surface area was small due to femoral cysts and small component size. We assessed the influence of these changes on complication rates in the first cohort of 292 patients and the second of 724, and then compared these outcomes in the second cohort with historical reports of resurfacing. We had a minimum followup of 24 months (mean, 33 months; range, 24-60 months). After changes were made in the indications and technique, the overall complication rate decreased from 13.4% to 2.1% with the femoral neck fracture rate reduced from 7.2% to 0.8%. The outcomes of the second cohort compare with modern-day resurfacing devices and appear superior to historical results. The data suggest patients should be carefully selected and technique optimized to reduce complications. Long-term followup is required to see if these promising results will be maintained.


Using Brain Oscillations and Corticospinal Excitability to Understand and Predict Post-Stroke Motor Function.
What determines motor recovery in stroke is still unknown and finding markers that could predict and improve stroke recovery is a challenge. In this study, we aimed at understanding the neural mechanisms of motor function recovery after stroke using neurophysiological markers by means of cortical excitability (transcranial magnetic stimulation-TMS) and brain oscillations (electroencephalography-EEG). In this cross-sectional study, 55 subjects with chronic stroke (62 ± 14 yo, 17 women, 32 ± 42 months post-stroke) were recruited in two sites. We analyzed TMS measures (i.e., motor threshold-MT-of the affected and unaffected sides) and EEG variables (i.e., power spectrum in different frequency bands and different brain regions of the affected and unaffected hemispheres) and their correlation with motor impairment as measured by Fugl-Meyer. Multiple univariate and multivariate linear regression analyses were performed to identify the predictors of good motor function. A significant interaction effect of MT in the affected hemisphere and power in beta bandwidth over the central region for both affected and unaffected hemispheres was found. We identified that motor function positively correlates with beta rhythm over the central region of the unaffected hemisphere, while it negatively correlates with beta rhythm in the affected hemisphere. Our results suggest that cortical activity in the affected and unaffected hemisphere measured by EEG provides new insights on the association between high-frequency rhythms and motor impairment, highlighting the role of an excess of beta in the affected central cortical region in poor motor function in stroke recovery.


Annexin A1 as a target for managing murine pristane-induced systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy. Annexin A1 (ANX A1) is expressed by many cell types and binds to phospholipids in a Ca2+ dependent manner. Abnormal expression of ANX A1 was found on activated B and T cells in both murine and human autoimmunity, suggesting its potential role as a therapeutic target. While its role on T lymphocytes is through formyl peptide receptor-like molecules (FPRL), and the formed ANX A1/FPRL pathway modulates T cell receptor signalling, there is still no fool-proof data available for the role of ANX A1 in B cells. We employed a lupus model of Balb/c mice with pristane-induced SLE which very closely resembles human lupus. In the present study, we investigated the possibility to modulate the autoimmune response in a pristane-induced mouse model of SLE using an anti- ANX A1 antibody. Administration of this monoclonal antibody resulted in the inhibition of T-cell activation and proliferation, suppression of IgG anti-dsDNA antibody-secreting plasma cells and of proteinuria, decreased disease activity and prolonged survival compared to control group.


[Thromboxane A2: Mechanisms of Synthesis and Intracellular Signaling System of Realization].
One of major complications of ischemic heart disease is myocardial infarction, which develops as a result of thrombosis at the site of ruptured atherosclerotic plaque. Platelets activation and aggregation are the key events of this process. The efficiency of aspirin and/or clopidogrel use is limited by residual platelet reactivity what indicates the need to explore its mechanisms. This review covers intracellular signaling systems involved in realization of effects of the main platelet agonists in order to specify new molecules for the target therapy in case of aspirin resistance.


Postgastrectomy polyneuropathy with thiamine deficiency is identical to beriberi neuropathy.
We assessed whether postgastrectomy polyneuropathy associated with thiamine deficiency is clinicopathologically identical to beriberi neuropathy, including a biochemical determination of thiamine status. Clinicopathologic features of 17 patients who had postgastrectomy polyneuropathy with thiamine deficiency were compared with those of 11 patients who had thiamine-deficiency neuropathy caused by dietary imbalance. The typical presentation for the two etiologies was as a symmetric sensorimotor polyneuropathy predominantly involving the lower limbs. A variety of clinical features, including neuropathic symptoms, progression, and coexistence of heart failure or Wernicke's encephalopathy, was seen similarly in both conditions. In both groups, the main electrophysiologic findings were those of axonal neuropathy, most prominently in the lower limbs. Sural nerve biopsy specimens also indicated axonal degeneration in both groups. Subperineurial edema was commonly observed. This study showed that thiamine-deficiency neuropathies due to gastrectomy and dietary imbalance are identical despite variability in their clinicopathologic features and suggested that thiamine deficiency can be a major cause of postgastrectomy polyneuropathy.


Traceless solid-phase synthesis of N1,N7-disubstituted purines.
A highly regioselective and traceless solid-phase route to N1,N7-disubstituted purines has been developed. Key steps in the reaction strategy involves (i) coupling of 6-chloropurine to the REM resin (Michael addition), (ii) oxidation, (iii) N1-alkylation, (iv) quaternization, and (v) product release through Hofmann elimination. A library of 15 N1,N7-disubstituted purines was synthesized.


Accelerating ion/electron transport by engineering an indium-based heterostructure toward large and reversible lithium storage.
The high activity of the In2O3/In2S3 heterostructure can be activated into homogeneous In2OxS3-x nanodots, thereupon stabilizing the subsequent cycles. The In2O3/In2S3 can offer a high capacity of 1140 mA h g-1 at 0.1 A g-1 after 290 cycles, and even at 1 A g-1, it harvests a reversible capacity of 900 mA h g-1 after 600 cycles.


[Outcomes of hip replacement: a hospital-based longitudinal study in Lazio region (Italy)].
Hip replacement (HR) is a very effective procedure for chronic hip diseases especially in elderly. The aims of this study were: 1) to describe the typology of HRs; 2) to assess short and long term outcomes; 3) to evaluate the relationship between both individual and hospital characteristics with the outcomes. Regional hospital discharge data and mortality register were used. The study population included residents of the Lazio region, over 17 years of age, who underwent HR in any private or public hospital in Italy. We used logistic regression analysis to examine in-hospital mortality, 30-day mortality, 90-day mortality. Cox regression analysis was run to investigate revision and 3-5 year mortality. Out of 8159 HRs, 69.5% were total hip replacements (THR) conducted predominantly on females over 70 years of age. We observed 262 in-hospital deaths (7.4% endoprothesis, 1.4% THR). Thirty and 90-day mortality also showed a different pattern among the two procedures (endoprothesis 8.0% and 15.8%, THR 1.3% and 2.2%). At the end of the follow-up, 21% of patients had died and 204 revisions had been carried out (1.4% endoprothesis, 3.0% THR). Overall, 1898 patients (23.3%) had a revision or died. The main short and long term mortality risk factors were: age, male gender and comorbidities. Hospital volume was not associated with a significant mortality risk. For endoprothesis, waiting time before surgery longer than 7 days was associated with a 30-day mortality risk of 2.83. The present study prompted us to test methodologies to evaluate quality levels in orthopaedic surgery units throughout the region using information systems. Further studies are needed to better understand the variability in the characteristics of care that emerged in Lazio hospitals.


A Correlation of Serum Histamine and Mast Cell Count with the Established Prognosticators in Oral Cancer.
We undertook this study in view of the rising interest in the interactions between tumor cells and mast cells in the tumor microenvironment and the mounting evidence of the role of mast cells in the prognosis of various cancers. The aim of the study is to determine the prognostic utility of mast cells and their mediators in oral squamous cell carcinoma (OSCC). This is a cross-sectional analytical study. A total of 41 cases were studied for determining the correlation of mast cell counts with histopathological prognostic variables and 29 cases for determining the serum histamine levels and to further correlate the values with the histopathologic determinants. Mast cell assessment was done using Toluidine blue stain on tissue sections while histopathological prognostic factors were evaluated with routine stains. The serum histamine levels were obtained by sandwich enzyme linked immunosorbent assay (ELISA). Mann-Whitney U-test was used to test the difference between parameters and a Spearman correlation coefficient was used. P < 0.05 was considered significant for statistical analysis. We found statistically significant correlations between increased median mast cell counts and higher grade of tumor, presence of lymphovascular invasion, greater depth of invasion, and presence of regional lymph node involvement. The serum histamine values correlated only with the depth of tumor invasion. Hence, as per our results, we suggest the use of mast cell counts in OSCC cases as a prognostic indicator in conjunction with other clinicopathological factors. At the same time, we acknowledge the fact that extensive studies are required to establish the role of mast cell mediators in the prognostic curve of oral cancer patients.


Role of perioperative parenteral nutrition in severely malnourished patients with Crohn's disease.
To evaluate the effect of perioperative parenteral nutrition on serum immunoglobulin, weight change, and post-operative outcome in severely malnourished patients with Crohn's disease. Thirty-two severely malnourished patients with Crohn's disease who had undergone surgery in our hospital were reviewed. Sixteen patients who received perioperative parenteral nutrition were enrolled in the study group, and the other 16 patients who did not receive parenteral nutrition were enrolled in the control group. Serum immunoglobulin, body mass index (BMI), liver function, weight change, and postoperative complications were evaluated. Serum IgM levels elevated 1 wk before surgery in both groups, and decreased to normal value (from 139+/-41 to 105+/-29 mg/dL, P = 0.04) 4 wk after operation in the study group, while no significant changes was noted in the control group (from 133+/-16 to 129+/-13 mg/dL, P = 0.34). There were no significant changes in concentrations of IgG and IgA. The BMI of the study group increased from 13.9+/-0.6 to 15.3+/-0.7 kg/m(2) (P = 0.02) with no significant change in the control group (14.1+/-0.7 and 14.5+/-0.5, respectively, P = 0.81). The percentage of resuming work was higher in the study group than in the control group. Perioperative parenteral nutrition possibly ameliorates the humoral immunity, reverses malnutrition, and facilitates rehabilitation.


Synthesis and Nanofiltration Membrane Performance of Oriented Mesoporous Silica Thin Films on Macroporous Supports.
Silica thin films with accessible hexagonal close-packed (HCP) pores have been deposited on macroporous supports to achieve composite nanofiltration membranes. The properties of these pore channels have been characterized through solvent flux and solute diffusion experiments. A chemically neutral surface (provided by a cross-linked layer of P123 copolymer) for silica thin film synthesis on the alumina macroporous support promotes the alignment of HCP channels vertical to the substrate, where the mesopore templating agent is block copolymer P123 (poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)). Vertical pore alignment is achieved for thin films (less than ∼100 nm) on a neutral surface and by sandwiching thicker films (∼240 nm) between two chemically neutral surfaces. Solvent flux through the composite membranes is consistent with accessible 10 nm diameter pores. Size selectivity of the membranes is characterized from the permeability of fluorescently tagged solutes (ranging from 4000 to 70 000 Da), where a size cut off occurs at 69 000 Da for the model protein bovine serum albumin. These permeability studies of the nanofiltration membranes serve to demonstrate solute transport in oriented silica thin film membranes and also highlight their versatility for membrane-based separations.


[Long-term results of a trial of short-term chemotherapy. French study 6.9.12].
The relapse rate after short course chemotherapy is usually assessed by cases that are available for analysis, with a delay which rarely exceeds 3 years from the time of instituting therapy. This level may be disputed if too many are lost to follow up or non-compliers appearing late. To understand the true failure rate we strove to trace every patient in a trial carried out between 1969 and 1973, consisting of three groups of patients treated with the same chemotherapy: Isoniazid (450 mg/day), Rifampicin (600 mg/day) given every day but for differing durations: 6 months (Group A), 9 months (Group B), 12 months (Group C), with either daily Ethambutol or Streptomycin in addition for the first three months. Amongst the 356 patients in the trial 86 were eliminated for failure to comply with the protocol, either due to a mishap or change of treatment. Amongst the 270 remaining patients, 248 were traced with a mean delay of post-therapy follow up of 101 months for patients still living and of 72 months for patients who had died in the intervening period, but of non-tuberculous disease. In the 242 old patients whose disease could be evaluated, the number of bacteriological relapses was 4/81 (6.2 %) in group A, and 2/85 (2.3 %) in group B and 2/76 (2.6 %) in group C. There was no significant differences between the groups. From these results it is seen that the Isoniazid/Rifampicin combination given daily for 6 months is a powerful combination with few failures. Maintaining such chemotherapy for 12 months does not seem to yield substantial gains. In conclusion nine months of chemotherapy with this regime offers a sufficiently ample guarantee of cure.


Wilderness Medical Society practice guidelines for the prevention and treatment of heat-related illness: 2014 update.
The Wilderness Medical Society (WMS) convened an expert panel to develop a set of evidence-based guidelines for the recognition, prevention, and treatment of heat illness. We present a review of the classifications, pathophysiology, and evidence-based guidelines for planning and preventive measures as well as best practice recommendations for both field and hospital-based therapeutic management of heat illness. These recommendations are graded on the basis of the quality of supporting evidence, and balance between the benefits and risks or burdens for each modality. This is an updated version of the original WMS Practice Guidelines for the Prevention and Treatment of Heat-Related Illness published in Wilderness & Environmental Medicine 2013;24(4):351-361.


Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes.
Protein interacting with c kinase 1 (PICK1) regulates the trafficking of receptors and ion-channels such as AMPA receptors. Traditionally, the PICK1 PDZ domain is regarded as an adaptor capable of binding to receptors trafficked by PICK1, and the lipid-binding BAR domain functions to tether PICK1 directly to membranes. Here, we show that the PICK1 PDZ domain can directly interact with lipid membranes. The PDZ domain and lipid membrane interaction is mediated by both a polybasic amino-acid cluster and a conserved 'Cys-Pro-Cys' motif located away from the peptide ligand-binding groove. Disruption of the PDZ and lipid membrane interaction totally abolished synaptic targeting of PICK1. Although mutation of the CPC motif did not affect the interaction between PICK1 and AMPA receptors, the mutant PICK1 was unable to cluster the GluR2 subunit of the receptor. In neurons, PICK1 containing the same mutation displayed dramatically compromised capacity in the trafficking of AMPA receptors. Taken together, our findings not only uncovered the novel lipid membrane-binding property of the PICK1 PDZ domain, but also provided direct evidence supporting the functional relevance of the PDZ-lipid interaction.