Preferential adhesion of silver nanoparticles onto crystal faces of alpha-cyclodextrin/carboxylic acids inclusion compounds.
Alpha-Cyclodextrin (alpha-CD) inclusion compounds containing the carboxylic acids (octanoic, decanoic, lauric or dodecanoic, myristic or tetradecanoic, palmitic or hexadecanoic and stearic or octadecanoic) as guests were synthesized and applied for preferential adhesion of silver nanoparticles (AgNPs). The binding affinity depends of the chain length of the respective guest and is most efficient for octanoic and decanoic acids. The immobilization of nanoparticles is caused by the spatial replacing of the stabilized shell of the nanoparticles by COOH groups of the guests molecules, located at the entrance of cavity of alpha-CD, corresponding to the {001} crystal plane. Crystalline coating with nanoparticles provides a means of storing of AgNPs on solids state without aggregation. The stabilization of the particles on the surface is valid for a given length and ordering of the guest in the cavities of the alpha-CD being the octanoic and decanoic acid the most appropriated.


Distribution of radioactive cesium and stable cesium in cattle kept on a highly contaminated area of Fukushima nuclear accident.
Radioactivity inspection of slaughtered cattle is generally conducted using a portion of the neck muscle; however, there is limited information about the distribution of radioactive cesium in cattle. In this study, therefore, we measured not only radioactive cesium but also stable cesium in various tissues of 19 cattle that had been kept in the area highly contaminated by the Fukushima nuclear accident. Skeletal muscles showed approximately 1.5-3.0 times higher concentration of radioactive cesium than internal organs. Radioactive cesium concentration in the tenderloin and top round was about 1.2 times as high as that in the neck muscle. The kidney showed the highest concentration of radioactive cesium among internal organs, whereas the liver was lowest. Radioactive cesium concentration in the blood was about 8% of that in the neck muscle. Characteristics of stable cesium distribution were almost the same as those of radioactive cesium. Correlation coefficient between radioactive cesium and stable cesium in tissues of individual cattle was 0.981 ± 0.012. When a suspicious level near 100 Bq/kg is detected in the neck of slaughtered cattle, re-inspection should be conducted using a different region of muscle, for example top round, to prevent marketing of beef that violates the Food Sanitation Act.


[H.C. Andersen: the story of a mother].
Death is inevitable the end of life. This has been described numerous times in the literature. In the Danish literature Hans Christian Andersen (1805-75) has in The Story of a Mother (1847) described a mother who sacrificed life for her child. According to Andersen death is not an affliction, but a confident faithful Providence favoured by God.


Assessment of the Effects of Total Emission Control Policies on Surface Water Quality in China: 2004 to 2014.
Water quality deterioration is a problem throughout the globe, especially in China. The Chinese government established national total emission control (TEC) policies related to the nation's surface water quality over the past 10 yr to restore, protect, and promote healthy water quality. The objective of this study is to evaluate the effects of China's TEC policies by analyzing three water quality constituents (ammonium nitrogen [NH-N], dissolved oxygen [DO], and the permanganate index [COD]) at 73 monitoring stations, which account for most of the surface waters of eastern China. The seasonal Mann-Kendall test revealed that approximately 60, 50, and 65% of stations had nonsignificant trends for COD, NH-N, and DO, respectively. Concentrations of COD and NH-N significantly (α = 0.05) decreased by 27.4 and 38.4% at the monitoring stations over the 11-yr study period, whereas DO significantly (α = 0.05) increased by 24.7%. Correlation analysis indicated that the water quality improved at approximately 30% (COD) and 20% (NH-N) of monitoring sites with the reduction of water pollutant emissions from industrial sources. A seasonal pattern was observed for the three water quality parameters at most of the stations but not at a regional scale. Results also indicated that COD concentrations decreased significantly (α = 0.05) at most river stations but increased significantly (α = 0.05) at nearly all lake stations, suggesting that TEC in China might be more effective for rivers than for lakes and reservoirs. Although there are many nonsignificant relationships with the water quality constituents selected as top pollutants in China, a few noticeable significant relationships were established.


Conformational studies of Escherichia coli ribosomes with the use of acridine orange as a probe.
The interaction of E. coli vacant ribosomes with acridine orange (AO) was studied, to obtain conformational information about rRNAs in ribosomes. Acridine orange binds to an RNA in two different modes: cooperative outside binding with stacking of bound AO's and intercalation between nucleotide bases. Free 16S and 23S rRNAs have almost identical affinities to AO. At 1 mM Mg2+, AO can achieve stacking binding on about 40% of rRNA phosphate groups. The number of stacking binding sites falls to about 1/3 in the 30S subunit in comparison with free 16S rRNA. In the 50S subunit, the number of stacking binding sites is only 1/5 in comparison with free 23S rRNA. Mg2+ ions are more inhibitory for the binding of AO to ribosomes than to free rRNAs. The strength of stacking binding appears to be more markedly reduced by Mg2+ in active ribosomes than in rRNAs. "Tight couple" 70S particles are less accessible for stacking binding than free subunits. The 30S subunits that have irreversibly lost the capability for 70S formation under low Mg2+ conditions have an affinity to AO that is very different from that of active 30S but similar to that of free rRNA, though the number of stacking binding sites is little changed by the inactivation. 70S and 30S ribosomes with stacking bound AO's have normal sedimentation constants, but the 50S subunits reversibly form aggregates.


Fine-tuning the fluorescence emission wavelength of gold nanoclusters in the protein-directed synthesis: the effect of silver ions.
Highly fluorescent gold nanoclusters have attracted much attention recently. Here, we reported a "green", facile method for fine-tuning the fluorescence emission wavelength of gold nanoclusters synthesized with bovine serum albumin (BSA). The principle of the experimental work involved the utilization of BSA as the reductant for the synthesis of gold nanoclusters and the addition of small amounts of silver ions in the synthesis process for tuning the fluorescence properties of the synthesized gold nanoclusters. Our results showed that fluorescence emission wavelength of the synthesized gold nanoclusters could be fine-tuned in a fairly wide range (- 90 nm) by addition of different quantities of silver nitrate in the synthesis process. In addition, with increasing silver ions quantity the emission wavelength of the gold nanoclusters varied in a non-monotonic manner. In this way, gold nanoclusters emitting yellow, orange or red fluorescence with decent quantum yields were readily obtained in a single batch.


Strategies for the prevention of stigma in psychiatry: Perspectives on local Psychiatric Rehabilitation.
The author, along the many years of her experience about psychiatric clinical cases on the community work, has acquired expertise in the field psychiatric rehabilitation and prevention of psychological discomfort or psychiatric disorder. Particular attention she and har team have always put the issue ok killing of the stigma and prejudice about mental illness, also through an invilment of the general populazion, school and etc. Her Experiences has shown that all of the strategies, as well as drug therapies and psycoterapies, improve recovery.


Standard Binding Free Energy and Membrane Desorption Mechanism for a Phospholipase C.
Peripheral membrane proteins (PMPs) bind temporarily to cellular membranes and play important roles in signaling, lipid metabolism, and membrane trafficking. Obtaining accurate membrane-PMP affinities using experimental techniques is more challenging than for protein-ligand affinities in an aqueous solution. At the theoretical level, calculation of the standard protein-membrane binding free energy using molecular dynamics simulations remains a daunting challenge owing to the size of the biological objects at play, the slow lipid diffusion, and the large variation in configurational entropy that accompanies the binding process. To overcome these challenges, we used a computational framework relying on a series of potential-of-mean-force (PMF) calculations including a set of geometrical restraints on collective variables. This methodology allowed us to determine the standard binding free energy of a PMP to a phospholipid bilayer using an all-atom force field. Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (BtPI-PLC) was chosen due to its importance as a virulence factor and owing to the host of experimental affinity data available. We computed a standard binding free energy of -8.2 ± 1.4 kcal/mol in reasonable agreement with the reported experimental values (-6.6 ± 0.2 kcal/mol). In light of the 2.3-μs separation PMF calculation, we investigated the mechanism whereby BtPI-PLC disengages from interactions with the lipid bilayer during separation. We describe how a short amphipathic helix engages in transitory interactions to ease the passage of its hydrophobes through the interfacial region upon desorption from the bilayer.


Role for HLA in susceptibility to infectious mononucleosis.
Factors involved in determining whether infectious mononucleosis occurs after primary EBV infection may include age, dose of virus received, and various genetic markers. A study by McAulay and colleagues reported in this issue of the JCI shows that the presence of certain HLA class I alleles correlates with the incidence and severity of infectious mononucleosis. These same HLA alleles are also risk factors for EBV-associated Hodgkin lymphoma (HL), supporting recent epidemiology that indicates that a history of infectious mononucleosis predisposes to HL. Recent studies suggest that an EBV vaccine might help to prevent infectious mononucleosis, and further development of this should now be considered.


Relationship between corticosteroid exposure and plasma lipid levels in heart transplant recipients.
Accelerated coronary atherosclerosis is a major cause of heart graft failure two years and more after heart transplantation, yet its etiology remains undetermined. We conducted this study to determine the prevalence of coronary risk-associated lipid abnormalities, and the relationship between lipid levels and exposure to corticosteroids and cyclosporine, in heart transplant recipients. The records of 92 consecutive heart transplant recipients from three different transplantation centers were reviewed. Patients from the three centers varied in age, in corticosteroid regimens, and in the proportion undergoing transplantation for ischemic cardiomyopathy. Although 11 patients were not receiving corticosteroids at the time of the study, all patients had received them immediately after transplantation. In addition to information pertaining to demographics, pretransplant medical history, rejection episodes, drug doses, renal function, and blood glucose levels, data on dietary intake and body weight were collected and plasma lipid levels were measured at the time of record review. A significant number, 48 (52 percent), of heart transplant recipients were above the sex- and age-adjusted 75th percentile, and 35 (38 percent) were above the 90th percentile for total cholesterol in comparison with a general reference population. Similar elevations were found in low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Bivariate analysis demonstrated cumulative prednisone exposure (r = 0.40, p = 0.0001) and cumulative cyclosporine exposure (r = 0.22, p = 0.04) but not diet or etiology of pretransplant heart disease to be significantly associated with age- or sex-adjusted total cholesterol percentiles. Low-density lipoprotein cholesterol percentiles were also correlated with cumulative prednisone (r = 0.37, p = 0.001) and cumulative cyclosporine exposure (r = 0.24, p = 0.02). Stepwise multiple linear regression analysis, however, demonstrated cumulative prednisone exposure to be the strongest predictor of both total and low-density lipoprotein cholesterol levels and percentiles (p = 0.0001), independent of cumulative cyclosporine exposure and other clinical variables. These data suggest that long-term corticosteroid exposure may result in an increased prevalence of unfavorable lipid profiles in heart transplant recipients.


Th1-mediated immunity against Helicobacter pylori can compensate for lack of Th17 cells and can protect mice in the absence of immunization.
Helicobacter pylori (H. pylori) infection can be significantly reduced by immunization in mice. Th17 cells play an essential role in the protective immune response. Th1 immunity has also been demonstrated to play a role in the protective immune response and can compensate in the absence of IL-17. To further address the potential of Th1 immunity, we investigated the efficacy of immunization in mice deficient in IL-23p19, a cytokine that promotes Th17 cell development. We also examined the course of Helicobacter infection in unimmunized mice treated with Th1 promoting cytokine IL-12. C57BL/6, IL-12 p35 KO, and IL-23 p19 KO mice were immunized and challenged with H. pylori. Protective immunity was evaluated by CFU determination and QPCR on gastric biopsies. Gastric and splenic IL-17 and IFNγ levels were determined by PCR or by ELISA. Balb/c mice were infected with H. felis and treated with IL-12 therapy and the resulting gastric bacterial load and inflammatory response were assessed by histologic evaluation. Vaccine induced reductions in bacterial load that were comparable to wild type mice were observed in both IL-12 p35 and IL-23 p19 KO mice. In the absence of IL-23 p19, IL-17 levels remained low but IFNγ levels increased significantly in both immunized challenged and unimmunized/challenged mice. Additionally, treatment of H. felis-infected Balb/c mice with IL-12 resulted in increased gastric inflammation and the eradication of bacteria in most mice. These data suggest that Th1 immunity can compensate for the lack of IL-23 mediated Th17 responses, and that protective Th1 immunity can be induced in the absence of immunization through cytokine therapy of the infected host.


Effect of dietary level of rumen-degraded protein on production and nitrogen metabolism in lactating dairy cows.
Twenty-eight (8 with ruminal cannulas) lactating Holstein cows were assigned to 4 x 4 Latin squares and fed diets with different levels of rumen-degraded protein (RDP) to study the effect of RDP on production and N metabolism. Diets contained [dry matter (DM) basis] 37% corn silage, 13% alfalfa silage, and 50% concentrate. The concentrate contained solvent and lignosulfonate-treated soybean meal and urea, and was adjusted to provide RDP at: 13.2, 12.3, 11.7, and 10.6% of DM in diets A to D, respectively. Intake of DM and yield of milk, fat-corrected milk, and fat were not affected by treatments. Dietary RDP had positive linear effects on milk true protein content and microbial non-ammonia N (NAN) flow at the omasal canal, and a quadratic effect on true protein yield, with maximal protein production at 12.3% RDP. However, dietary RDP had a positive linear effect on total N excretion, with urinary N accounting for most of the increase, and a negative linear effect on environmental N efficiency (kg of milk produced per kg of N excreted). Therefore, a compromise between profitability and environmental quality was achieved at a dietary RDP level of 11.7% of DM. Observed microbial NAN flow and RDP supply were higher and RUP flow was lower than those predicted by the NRC (2001) model. The NRC (2001) model overpredicted production responses to RUP compared with the results in this study. Replacing default NRC degradation rates for protein supplements with rates measured in vivo resulted in similar observed and predicted values, suggesting that in situ degradation rates used by the NRC are slower than apparent rates in this study.


Pseudo-dislocation of the sternoclavicular joint.
Fractures of the medial third of the clavicle are the rarest of all clavicle fractures. We present two cases of medial clavicle fracture nonunions that were initially thought to be chronic anterior sternoclavicular dislocations and describe the entity of pseudo-dislocation of the sternoclavicular joint. Computed tomography should be performed on all patients with suspected or established injuries of the sternoclavicular region to ensure differentiation between fracture and dislocation.


Reflection suppression by polarization in backscatter LDA measurements near walls and in two-phase flows.
A method is proposed and verified by experiments to suppress disturbing reflections in laser Dodppler anemometer (LDA) measurements. Disturbing reflections occur in a variety of practical applications of LDA, such as backscatter measurements near walls or in two-phase fluid or particle velocity measurements. The method uses circularly polarized light that changes the handedness when reflected and is quenched by a suitably oriented polarization analyzer. Scattered light, however, is partially transmitted by the analyzer to give undisturbed seeding particle signals. Verification experiments have been performed to demonstrate the method; systems for practical applications are proposed.


Coordinating expression of RNA binding proteins with their mRNA targets.
Post-transcriptional regulation by RNA binding proteins (RBPs) plays prominent roles in a variety of biological processes. In this study, by analyzing the global regulatory relationship between RBPs and their target mRNAs in yeast, we discovered that most RBP genes are co-regulated with their target genes, but the RBPs tend to dampen expression variation among their target mRNAs. We further examined a well-studied RBP gene, PUF3, and found that the protein decreases the variation of its target mRNAs by differentially affecting their decay. We also constructed a mathematical model to explain the relationship between RBPs and the expression of their target genes. Our results provided new insights into the functional importance of RBPs in coordinating the expression of their target genes.


Abnormalities of the Optic Nerve in Down Syndrome and Associations With Visual Acuity.
Background: Various ocular anomalies are present in the vast majority of individuals with Down syndrome; however, we know little about optic nerve abnormalities. The aim of this cross-sectional comparative study was to describe optic disc morphology in patients with Down syndrome and to determine if the differences found are potentially related to visual acuity. Subjects/methods: Assessable fundus images were obtained in 50 children with Down syndrome and 52 children without Down syndrome. Morphological analysis of the optic nerve was performed, including the disc-to-macula distance (DM) to disc diameter (DD) ratio (DM/DD), the cup-to-disc ratio and optic disc ovality. Data relating to ophthalmological status were retrospectively analyzed to evaluate the possible causes of reduced visual acuity. Results: DM/DD was significantly larger (p = 0.0036) and the cup-to-disc ratio was significantly smaller (p = 0.018) in children with Down syndrome, compared to controls. The optic discs were also more frequently torted (p = 0.034), tilted (p = 0.0049) and oval (p = 0.026). Furthermore, crescents (p = 0.0002), peripapillary atrophy (p = 0.0009), and pigment anomalies (p < 0.0001) were also more prevalent in children with Down syndrome than in those without. Visual acuity was significantly lower in children with Down syndrome compared to controls with similar refraction problems and strabismus prevalence (p < 0.0001). The mean DM/DD and the presence of a crescent was not directly related to visual acuity (r = 0.39, p = 0.31), (r = 0.35, p = 0.12) respectively. Visual acuity was diminished in 80% of children with Down syndrome and the smallest discs and in 84% of those with tilted discs. However, other causes may contribute to the diminished visual acuity in these cases. Conclusion: The optic nerve head in children with Down syndrome is affected by various anatomical and developmental abnormalities. Unrelated to refraction (spherical equivalent), the optic discs appear smaller and more frequently mal-inserted in Down syndrome. Optic disc hypoplasia, as well as severe tilting, may reduce vision but they do not represent major contributors to the decrease of vision in such children. As these children often have multiple ocular and neurosensory problems, it remains challenging to relate visual acuity problems with a specific abnormality. Smaller discs may lead to optic disc drusen formation in children with Down syndrome.


Effect of toothbrush stimulation on temperature of gingival and alveolar mucosae.
Thermometry was used to study the effect of applying a toothbrush to three types of oral mucosae, in forty dental students. Brushing with an electric tooth brush resulted in an immediate fall in temperature, but 3 min later the temperature was significantly higher than before stimulation. The temperature changes were greater in gingival crevice and attached gingiva compared with alveolar mucosa. Moreover, it was found that a static application of the toothbrush produced temperature changes which were equal to those following a dynamic application.


Electron attachment to PSCl3.
Electron attachment to PSCl3 was studied in 133-Pa pressure of helium gas at temperatures from 298-550 K. Measurements of rate constants and branching fractions were made in a flowing-afterglow Langmuir-probe (FALP) apparatus. These experiments yielded an electron attachment rate constant of 5.1 x 10(-8) cm3 s(-1) that was found not to change significantly in the 298-550 K temperature range. This rate constant represents an attachment efficiency of about 14%. Attachment in 133 Pa of He gas yielded only the dissociative ion products PSCl2- and Cl-. The FALP data suggest that there is an activation energy of about 17 meV for production of PSCl2-. Attachment to PSCl3 was also studied at high pressure (9-93 kPa) of N2 in an ion mobility mass spectrometer, at 298 K. In contrast to the low-pressure data, the parent anion product channel (PSCl3-) was observed (along with the dissociative channels), and increased in importance with N2 pressure. Gaussian-3 (G3) calculations were carried out for PSCl3 and PSCl2 neutrals and anions to aid in interpretation of the experimental results. The calculations indicate that the electron affinity EA(PSCl2) is slightly smaller than EA(Cl), which may account for the observed branching fractions for PSCl2- and Cl- in the low-pressure experiments. A natural population analysis was performed to obtain the charges associated with each atom in the molecules in order to estimate how the attached electron is distributed. Comparison is made between the present study of electron attachment to PSCl3 and our earlier work on attachment to POCl3, and G3 calculations are reported here for neutral and anionic POCl2 and POCl3. In contrast to PSCl2, the calculations imply that EA(POCl2) is slightly greater than EA(Cl). For both PSCl3 and POCl3, the calculations show that the dissociative electron attachment process is close to thermoneutral.


Store-operated calcium channels: Potential target for the therapy of hypertension.
Effective therapy of hypertension represents a key strategy for reducing the burden of cardiovascular disease and its associated mortality. The significance of voltage dependent L-type Ca²⁺ channels to Ca²⁺ influx, and of their regulatory mechanisms in the development of heart disease, is well established. A wide variety of L-type Ca²⁺ channel inhibitors and Ca²⁺ antagonists have been found to be beneficial not only in the treatment of hypertension, but also in myocardial infarction and heart failure. Over the past two decades, another class of Ca²⁺ channel - the voltage independent store-operated Ca²⁺ channel - has been implicated in the regulation and fine tuning of Ca²⁺ entry in both cardiac and smooth muscle cells. Store-operated Ca²⁺ channels are activated by the depletion of Ca²⁺ stores within the endoplasmic/sarcoplasmic reticulum, or by low levels of cytosolic Ca²⁺, thereby facilitating agonist-induced Ca²⁺ influx. Store-operated Ca²⁺ entry through this pivotal pathway involves both stromal interaction molecule (STIM) and Orai channels. Different degrees of changes in these proteins are considered to promote Ca²⁺ entry and hence contribute to the pathogenesis of cardiovascular dysfunction. Several blockers of store-operated Ca²⁺ channels acting at the level of both STIM and Orai channels have been shown to depress Ca²⁺ influx and lower blood pressure. However, their specificity, safety, and clinical significance remain to be established. Thus, there is an ongoing challenge in the development of selective inhibitors of store-operated Ca²⁺ channels that act in vascular smooth muscles for the improved treatment of hypertension.


The radiographic pleural abnormalities in asbestos exposure: relationship to physiologic abnormalities.
The effects of asbestos-induced benign pleural conditions on pulmonary function have been controversial since this subject was first studied in the mid-1960s. Firm conclusions have been difficult to reach because of (1) the difficulty of taking into account asbestos exposure, which may have effects on pulmonary function other than those mediated through pleural lesions, (2) the disagreement over the type and extent of radiographic pleural abnormalities, (3) the imprecision in measuring pulmonary function, and (4) the numerous potential confounding factors of reduced pulmonary function, such as cigarette smoking, age, concurrent occupational exposures, and prior chest diseases or trauma. This article critically evaluates the published reports on the functional significance of asbestos-induced pleural conditions. The results of this analysis lead to the conclusion that (1) pleural plaques are not associated with clinically significant reductions in pulmonary function, (2) diffuse pleural thickening, when extensive, can severely impair ventilation, and (3) restriction with a preserved diffusing capacity is the expected pattern when pleural lesions are responsible for reduced pulmonary function.


The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake.
The cannabinoid 1 receptor (CB1R) has a well-established role in appetite regulation. Central CB1R antagonists, notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals, but were discontinued due to psychiatric side-effects. The CB1R is also expressed peripherally, where its effects include promotion of liver fat accumulation, which consumes ATP. Type 2 diabetes in obese subjects is linked to excess liver fat, whilst there is a negative correlation between hepatic ATP content and insulin resistance. A decreased hepatic ATP/AMP ratio increases food intake by signals via the vagus nerve to the brain. The hepatic cannabinoid system is highly upregulated in obesity, and the effects of hepatic CB1R activation include increased activity of lipogenic and gluconeogenic transcription factors. Thus, blockade of hepatic CB1Rs could contribute significantly to the weight-reducing and insulin-sensitizing effects of CB1R antagonists. Additionally, upregulation of the hepatic CB1R may contribute to chronic liver inflammation, fibrosis and cirrhosis from causes including obesity, alcoholism and viral hepatitis. Peripheral CB1R antagonists induce weight loss and metabolic improvements in obese rodents; however, as there is evidence that hepatic CB1Rs are predominately intracellular, due to high intrinsic clearance, many drugs may not effectively block these receptors and therefore have limited efficacy. Hepatoselective CB1R antagonists may be effective at reducing hepatic steatosis, insulin resistance and bodyweight in obese, diabetic patients, with far fewer side-effects than first-generation CB1R antagonists. Additionally, such compounds may be effective in treating inflammatory liver disease, such as non-alcoholic steatohepatitis, reducing the likelihood of disease progression to cirrhosis or cancer.


Fiber-reinforced framework and Ceromer restorations: a technical review.
The utilization of synthetic resins and ceramics in combination with metal frameworks continues to be the mainstay of crown and bridge prosthetics. Although most of these systems have resulted in years of clinical success, each material when used in combination has inherent properties that induce stresses to the system. The combination of ceramic technology and polymer research, in addition to fiber integration, has resulted in the development and introduction of a new category of crown and bridge materials--a ceromer and fiber-reinforced restorative system. This article examines the history of polymer and ceramic technology, and reports the clinical and research data currently available on one indirect ceromer system (Targis System, Ivoclar Williams, Amherst, NY).


Alzheimer's disease: The role for neurosurgery.
Dementia, most commonly caused by Alzheimer's disease (AD), affects approximately 35 million people worldwide, with the incidence expected to increase as the population ages. After decades of investigation, AD is now understood to be a complex disease that affects behavior and cognition through several mechanisms: Disrupted neuronal communication, abnormal regional tissue metabolism, and impaired cellular repair. Existing therapies have demonstrated limited efficacy, which has spurred the search for specific disease markers and predictors as well as innovative therapeutic options. Deep brain stimulation (DBS) of the memory circuits is one such option, with early studies suggesting that modulation of neural activity in these networks may improve cognitive function. Encapsulated cell biodelivery (ECB) is a device that delivers nerve growth factor to the cholinergic basal forebrain to potentially improve cognitive decline in AD patients. This review discusses the pathogenesis of AD, novel neuroimaging and biochemical markers, and the emerging role for neurosurgical applications such as DBS and ECB.


Carnosine is neuroprotective against permanent focal cerebral ischemia in mice.
Carnosine is a naturally occurring dipeptide with multiple neuroprotective properties. In addition, it is well tolerated in high doses with minimal side effects. The purposes of this study were to determine whether carnosine is neuroprotective in permanent focal cerebral ischemia and to determine potential mechanisms of neuroprotection. We investigated the efficacy of carnosine in a mouse model of permanent focal cerebral ischemia. The effects of carnosine were investigated with respect to neuronal damage and infarct formation, endogenous antioxidant status, and matrix metalloproteinase activity. Carnosine significantly decreased infarct size and neuronal damage when administered at time points both before and after the induction of ischemia. Carnosine also decreased reactive oxygen species levels in the ischemic brain, preserved normal glutathione levels, and decreased matrix metalloproteinase protein levels and activity. Carnosine is neuroprotective in focal cerebral ischemia and appears to influence deleterious pathological processes that are activated after the onset of ischemia.


Non-standard radiotherapy fractionations delay the time to malignant transformation of low-grade gliomas.
Grade II gliomas are slowly growing primary brain tumors that affect mostly young patients. Cytotoxic therapies (radiotherapy and/or chemotherapy) are used initially only for patients having a bad prognosis. These therapies are planned following the "maximum dose in minimum time" principle, i. e. the same schedule used for high-grade brain tumors in spite of their very different behavior. These tumors transform after a variable time into high-grade gliomas, which significantly decreases the patient's life expectancy. In this paper we study mathematical models describing the growth of grade II gliomas in response to radiotherapy. We find that protracted metronomic fractionations, i.e. therapeutical schedules enlarging the time interval between low-dose radiotherapy fractions, may lead to a better tumor control without an increase in toxicity. Other non-standard fractionations such as protracted or hypoprotracted schemes may also be beneficial. The potential survival improvement depends on the tumor's proliferation rate and can be even of the order of years. A conservative metronomic scheme, still being a suboptimal treatment, delays the time to malignant progression by at least one year when compared to the standard scheme.


Computational Prodrug Design Methodology for Liposome Formulability Enhancement of Small-Molecule APIs.
Encapsulation into liposomes is a formulation strategy that can improve efficacy and reduce side effects of active pharmaceutical ingredients (APIs) that exhibit poor biodistribution or pharmacokinetics when administered alone. However, many APIs are unsuitable for liposomal formulations intended for parenteral administration due to their inherent physicochemical properties─lipid bilayer permeability and water-lipid equilibrium partitioning coefficient. Too high permeability results in premature leakage from liposomes, while too low permeability means the API is not able to pass across biological barriers. There are several options for solving this issue: (i) change of the lipid bilayer composition, (ii) addition of a permeability enhancer, or (iii) modification of the chemical structure of the API to design a prodrug. The latter approach was taken in the present work, and the effect of small changes in the molecular structure of the API on its permeation rate across a lipidic bilayer was systematically explored utilizing computer simulations. An in silico methodology for prodrug design based on the COSMOperm approach has been proposed and applied to four APIs (abiraterone, cytarabine, 5-fluorouracil, and paliperidone). It is shown that the addition of aliphatic hydrocarbon chains via ester or amide bonds can render the molecule more lipophilic and increase its permeability by approximately 1 order of magnitude for each 2 carbon atoms added, while the formation of fructose adducts can provide a more hydrophilic character to the molecule and reduce its lipid partitioning. While partitioning was found to depend only on the size and type of the added group, permeability was found to depend also on the added group location. Overall, it has been shown that both permeability and lipid partitioning coefficient can be systematically shifted into the desired liposome formulability window by appropriate group contributions to the parental drug. This can significantly increase the portfolio of APIs for which liposome or lipid nanoparticle formulations become feasible.


Attitude and self-care practice on hypertension among antihypertensive medication users in a tertiary care hospital Nepal.
Hypertension a "silent killer" is a serious global health problem, whose prevalence is increasing in Nepal. This study aimed to determine the attitude and practice of hypertension among anti-hypertensive medication users in a tertiary care teaching hospital in western Nepal. A hospital-based cross-sectional study design was used among 136 hypertensive patients under medication, aged ⩾ 30 years, and visiting medical outpatient department, medical ward, and geriatric ward, using a non-probability convenience sampling technique. Semi-structured questionnaires were used for data collection through interviews. Descriptive and inferential statistics were used, and a p value < 0.05 was considered statistically significant. Most of the patients were male (56.6%), mean ± standard deviation age was 56.74 ± 12.58. Majority of them were Hindu (69.9%), upper caste people (29.4%), illiterate (22.1%), and house maker (27.2%). Half of the patients (50.7%) had a positive attitude and more than half (52.2%) had performed adequate self-care practice. Selected variables such as educational status and dietary pattern and attitude were significantly associated, whereas no association was found between sociodemographic variables and self-care practice. Attitude and self-care practices were found strongly associated with one another (p = 0.002). Our study found that half of the study population had positive attitude, and more than half of them had performed adequate self-care practice. Hence, educational interventions and awareness programs on dietary aspects should be focused for improving the attitude and practice of all the patient groups.


[Assessment of the effectiveness of uvulopalatopharyngoplasty (UPPP) in the treatment of mild and moderate OSA patients preliminarily selected for the procedure by simple clinical examination].
There is abundant conflicting information in the literature about prognostic value of sophisticated, diagnostic tests as well as data from simple clinical examination in its surgical treatment due to the complex nature of OSA. The aim of our study was to assess the efficacy of uvulopalatopharyngoplasty in the treatment of mild and moderate OSA patients who were preliminary selected by simple clinical examination. 20 patients with obstructive sleep apnea syndrome were included in this study. There were patients who met the following criteria: RDI less than 30, BMI less than 30, collar size less than 43 cm, normal nasal potency, modified Mallampati grade I or II, were enrolled in the study. The mean age of the patients was 45,5. Modified Mallampati score was used for evaluation the structures of oropharynx. 55% of patients were classified for grade I in Mallampati score and 45% of patients- grade II in this scale. At least 50% reduction of RDI after UPPP was observed in 75% of patients. The mean RDI was decreased from 21,35 in preoperative period to 9,85 in the control study. In 60% of our patients the RDI dropped to the value of less then 10. In 5% of the patients, the surgical treatment did not decrease at least 50% of RDI. However in this patient group, we observed a slight improvement of mean minimal saturation (from 84,1 +/- 3,8 to 86,2% +/- 3,6). Using simple clinical parameters for preliminary selection of patients with mild and moderate OSA enabled us to achieve considerably better success rate after UPPP.


"Culture Is So Interspersed": Child-Minders' and Health Workers' Perceptions of Childhood Obesity in South Africa.
Introduction. Forty-one million children globally are overweight or obese, with most rapid rate increases among low- and middle-income nations. Child-minders and health workers play a crucial role in obesity prevention efforts, but their perceptions of childhood obesity in low- and middle-income countries are poorly understood. This study aims to (1) explore child-minders and health workers' perceptions of the causes, consequences, potential strategies, and barriers for childhood obesity prevention and intervention in Cape Town, South Africa and (2) to provisionally test the fit of a socioecological framework to explain these perceptions. Methods. Twenty-one interviews were recorded, transcribed, and analyzed through analytic induction. Results. Participants identified multilevel factors and contexts, as well as potential consequences and priorities of interest in addressing childhood obesity. An adapted childhood obesity perceptions model was generated, which introduces an overarching cultural dimension embedded across levels of the socioecological framework. Conclusions. Culture plays a pivotal role in explaining obesogenic outcomes, and the results of this study demonstrate the need for further research investigating how obesity perceptions are shaped by cultural frames (e.g., social, political, and historical). Understanding the causes, consequences, and potential interventions to address obesity through a cultural lens is critical for promoting health in low- and middle-income nations.


Resistance exercise improves autonomic regulation at rest and haemodynamic response to exercise in non-alcoholic fatty liver disease.
Autonomic dysfunction has been reported in patients with NAFLD (non-alcoholic fatty liver disease) and is associated with clinical presentations. To date, there are no therapies to improve autonomic regulation in people with NAFLD. The present study defines the impact of a short-term exercise programme on cardiac autonomic and haemodynamic regulation in patients with NAFLD. A total of 17 patients with clinically defined NAFLD [age, 55±12 years; BMI (body mass index), 33±5 kg/m²; liver fat, 17±9%] were randomized to 8 weeks of resistance exercise or a control group to continue standard care. Resting and submaximal exercise (50% of peak oxygen consumption) autonomic and cardiac haemodynamic measures were assessed before and after the intervention. Resistance exercise resulted in a 14% reduction in HR (heart rate) and 7% lower SBP (systolic blood pressure) during submaximal exercise (16 beats/min, P=0.03 and 16 mmHg, P=0.22). Sympathovagal balance, expressed as LF/HF (low-frequency/high-frequency) ratio of the mean HR beat-to-beat (R-R) interval, was reduced by 37% (P=0.26). Similarly sympathovagal balance of DBP (diastolic blood pressure) and SBP variability decreased by 29% (P=0.33) and 19% (P=0.55), respectively in the exercise group only. BRS (baroreflex sensitivity) increased by 31% (P=0.08) following exercise. The mean R-R interval increased by 23% (159 ms, P=0.09). Parasympathetic regulation was decreased by 17% (P=0.05) and overall sympathovagal balance in BP regulation (LF/HF ratio) increased by 26% (P=0.02) following resistance exercise. Resting haemodynamic measures remained similar between groups. Resistance exercise therapy seems to improve autonomic and submaximal exercise haemodynamic regulation in NAFLD. Further studies are required to define its role in clinical management of the condition.


Intracellular human gamma-interferon triggers an antiviral state in transformed murine L cells.
Interaction of human gamma-interferon (IFN-gamma) with a cell-surface receptor is known to be essential for the cell to become resistant to viral infection. Here we demonstrate that IFN-gamma, when present inside the cell, is also capable of inducing a permanent antiviral state. Mouse cells transformed with a truncated human cDNA encoding a mature IFN-gamma protein lacking the signal peptide accumulate high levels of intracellular human IFN-gamma. Not only do these cells acquire a permanent resistance to viral infection, they also exhibit all the biochemical characteristics normally observed after exposure to exogenous IFN. The observed loss of species specificity normally associated with IFN-gamma suggests that this restriction is strictly dependent on the interaction of the molecule with the cell-surface receptor.


Systems approach to animal health services delivery in sub-Saharan Africa: concept development.
The current trend towards restructuring to improve the standards and efficiency of public services in sub-Saharan Africa, within the framework of economic structural adjustment programmes, has stimulated debates and proposals regarding veterinary services in the region. Such debates sometimes neglect the fact that a number of different animal production systems may coexist within a single economy. The authors review the concept of veterinary services delivery systems and examine this concept in the context of animal production systems, concluding that different delivery systems may be required to cater for different production systems. Planners and policy makers are urged to ensure that advocated changes are compatible with the existing animal production systems. This systems approach may be applied in considering various aspects of veterinary services, including animal health care delivery, animal health education and training, research, outreach work and financing.


IUPHAR themed review: Opioid efficacy, bias, and selectivity.
Drugs acting at the opioid receptor family are clinically used to treat chronic and acute pain, though they represent the second line of treatment behind GABA analogs, antidepressants and SSRI's. Within the opioid family mu and kappa opioid receptor are commonly targeted. However, activation of the mu opioid receptor has side effects of constipation, tolerance, dependence, euphoria, and respiratory depression; activation of the kappa opioid receptor leads to dysphoria and sedation. The side effects of mu opioid receptor activation have led to mu receptor drugs being widely abused with great overdose risk. For these reasons, newer safer opioid analgesics are in high demand. For many years a focus within the opioid field was finding drugs that activated the G protein pathway at mu opioid receptor, without activating the β-arrestin pathway, known as biased agonism. Recent advances have shown that this may not be the way forward to develop safer analgesics at mu opioid receptor, though there is still some promise at the kappa opioid receptor. Here we discuss recent novel approaches to develop safer opioid drugs including efficacy vs bias and fine-tuning receptor activation by targeting sub-pockets in the orthosteric site, we explore recent works on the structural basis of bias, and we put forward the suggestion that Gα subtype selectivity may be an exciting new area of interest.


Safety and efficacy of balloon kyphoplasty at 4 or more levels in a single anesthetic session.
OBJECTIVE In this case series, the authors evaluated the safety of balloon kyphoplasty at 4 or more vertebral levels in a single anesthetic session. The current standard is that no more than 3 levels should be cemented at one time because of a perceived risk of increased complications. METHODS A retrospective chart review was performed for 19 consecutive patients who underwent ≥ 4-level balloon kyphoplasty between July 1, 2011, and December 31, 2015. Outcomes documented included kyphoplasty-associated complications and incidences of subsequent vertebral fracture. RESULTS Nineteen patients aged 22 to 95 years (mean 66.1 years, median 66 years; 53% male, 47% female) had 4 or more vertebrae cemented during the same procedure (mean 4.6 levels [62 thoracic, 29 lumbar]). No postoperative anesthetic complication, infection, extensive blood loss, symptomatic cement leakage, pneumothorax, or new-onset anemia was observed. Five patients experienced new compression fracture within a mean of 278 days postoperatively. One patient with metastatic cancer suffered bilateral pulmonary embolism 19 days after surgery, but no evidence of cement in the pulmonary vasculature was found. CONCLUSIONS In this case series, kyphoplasty performed on 4 or more vertebral levels was not found to increase risk to patient safety, and it might decrease unnecessary risks associated with multiple operations. Also, morbidity associated with leaving some fractures untreated because of an unfounded fear of increased risk of complications might be decreased by treating 4 or more levels in the same anesthetic session.


The prognostic importance of right ventricular remodeling and the circadian blood pressure pattern on the long-term cardiovascular outcome.
We sought to investigate the predictive value of right ventricular (RV) remodeling and 24-h blood pressure (BP) patterns on long-term cardiovascular prognosis in the initially untreated hypertensive patients. The current study included 505 initially untreated hypertensive patients who were consequently included in this study from 2007 to 2012. All the patients underwent laboratory analysis, 24-h BP monitoring and echocardiographic examination at baseline. The patients were followed for a median period of 9 years. The adverse outcome was defined as the hospitalization due to cardiovascular events (atrial fibrillation, myocardial infarction, myocardial revascularization, heart failure, stroke, or cardiovascular death). During the 9-year follow-up period adverse cardiovascular events occurred in 82 hypertensive patients. Night-time SBP, the nondipping BP pattern, left ventricle hypertrophy, RV hypertrophy, right atrial enlargement, RV diastolic dysfunction, and RV systolic dysfunction were associated with adverse cardiovascular events. Nevertheless, night-time SBP, the nondipping BP pattern, mitral E/e', left ventricle hypertrophy, and RV hypertrophy were the only independent predictors of cardiovascular events. When all four BP patterns were included in the model, only the reverse dipping BP pattern was an independent predictor of cardiovascular events. The present investigation showed that RV hypertrophy and the reverse dipping BP pattern were independent long-term predictors of the cardiovascular outcome. Detailed echocardiographic evaluation and 24-h ambulatory blood pressure monitoring should be performed even in low-risk hypertensive patients.


99mTc technegas ventilation and perfusion lung scintigraphy for the diagnosis of pulmonary embolus.
Lung scintigraphy is used widely for diagnosis of pulmonary embolus (PE). Technegas ventilation imaging has many advantages over other methods, but little outcome data exists on this technique. The aims of this study were to better define the role of lung scintigraphy in the management of patients with suspected PE and to evaluate technegas ventilation imaging by following patient outcomes. A group of 717 out of 834 consecutive patients, referred to a university teaching hospital for lung scintigraphy to confirm or refute the diagnosis of PE, was followed for 18-30 mo to determine clinical outcome. The follow-up endpoints were death as a result of PE, death as a result of hemorrhage after treatment for PE, uncomplicated survival, survival with subsequent PE, nonfatal hemorrhage after treatment for PE and recurrence of PE in treated patients. Ventilation imaging was performed using technegas, and perfusion imaging was performed using intravenous 99mTc macroaggregated albumin. The modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) diagnostic criterion was used for interpretation of lung scintigraphy. Diagnostic results included 3.5% normal studies, 67.4% assessed as low probability for PE, 10% as moderate probability for PE and 19.1% as high probability for PE. A total of 231 patents received therapy with heparin, followed by warfarin, including those receiving anticoagulation therapy for other conditions. Ninety-six percent of patients with normal and low probability studies (n = 508) had good outcomes, 6 patients died as a result of PE and 12 subsequently developed PE. The odds ratio for death by PE in this group was 0.2. Of the 72 moderate probability studies, 39 patients were untreated. In this group there was 1 death due to PE, and PE subsequently developed in 2 patients. None of the remaining 33 treated patients died, but 4 patients experienced bleeding complications. The odds ratio for death by PE in the moderate probability group was 0.7. In those patients with high-probability studies, there were 8 deaths by PE, 6 deaths by hemorrhage, 11 nonfatal hemorrhages and 7 patients who experienced recurrences of PE. The odds ratios in this group were 6 and 10 for death by PE, or death by PE and the treatment of PE, respectively. The use of the modified PIOPED diagnostic classification is valid for technegas lung scintigraphy. Using technegas, normal/low-probability and high-probability results are highly predictive of respective outcomes. Technegas lung scintigraphy reduces the number of indeterminate studies.


A Full-Digital Technique to Mount a Maxillary Arch Scan on a Virtual Articulator.
Mounting casts accurately on an articulator is a prerequisite for the treatment planning/execution of complex dental cases that require occlusal rehabilitation. A full digital approach to transfer the position of maxillary dentition to a virtual articulator, by using intraoral scans and cone beam computed tomography (CBCT) files is presented. This technique offers reduced chairside time and the flexibility of choosing the orientation plane. It can be used in orthognathic surgeries, complex interdisciplinary treatments requiring a CBCT scan with a large field of view, or treatments that already have the head CT or CBCT scans from previous diagnosis/treatment.


Lung Cancer Detection from CT Images: Modified Adaptive Threshold Segmentation with Support Vector Machines and Artificial Neural Network Classifier.
The objective of the research is to implement an advanced modified threshold segmentation and classification model for early and accurate detection of lung cancer from CT images. Using the Support Vector Machines (SVM) classifier as well as the Artificial Neural Network (ANN) classifier, the authors propose using Modified adaptive threshold segmentation as a segmentation approach for cancer detection. Here, Lung Image Database Consortium (LIDC) datasets, a collection of CT scans, are used as the video frames in an investigation to authorize the recitation of the suggested technique. Both quantitative as well as qualitative analyses are used to analyze the segmentation function of the anticipated algorithm. Both the ANN and SVM classifiers used in the suggested technique for lung cancer diagnosis achieve world-record levels of accuracy, with the former achieving a 96.3% detection rate and the latter a 97% rate of accuracy. This innovation may have a major impact on the worldwide rate of lung cancer rate due to its ability to detect lung tumors in their earliest stages when they are most amenable to being avoided and treated. This method is useful because it provides more information and facilitates quick, precise decision-making for doctors diagnosing lung cancer in their patients.


Tennis elbow.
The term "tennis elbow" usually refers to lateral epicondylitis, but the same symptoms can be caused by pathologic processes in the elbow. In fact, most cases of this common condition are caused by occupational stress rather than racket sports. Patients complain of elbow pain when the wrist is extended against resistance or during repetitive actions with the wrist and elbow extended. The condition is thought to be caused by a lesion at the origin of the common wrist extensor mechanism, at or very near the lateral epicondyle of the humerus. Differential diagnosis includes inflammatory, arthritic and nerve entrapment syndromes. Prompt conservative treatment has a high success rate. Patient education, use of a tennis-elbow band and physical therapy play key roles in the management of acute symptoms and in the prevention of recurrence. Surgical intervention is required only when other treatment fails.


The French Sleep Disturbance Scale for Children.
The psychometric properties of the Sleep Disturbance Scale for Children (SDSC) have been shown to be accurate, even when translated into several languages. The aim of the present study was to translate, adapt, and validate the SDSC for a French-speaking population. After forward- and back-translation, the tool was further translated and adapted into the French language. It was then pretested in terms of clarity on 33 French-speaking parents. Pretesting demonstrated that the questionnaire was well understood, indicating good clarity. During the validation phase, a total of 447 French-speaking parents of children aged between 4 and 16 years completed the SDSC. Among these, 66 children were diagnosed with sleep disorders by a pediatric specialist after a sleep consultation and polysomnographic recordings. The factor analysis revealed five factors: difficulty in initiating and maintaining sleep (DIMS), sleep breathing disorders (SBD), disorders of excessive somnolence (DOES), parasomnias (PARA) and non-restorative sleep (NRS). This psychometric structure is reliable and logical in comparison with the experts' diagnoses. Convergent validity, divergent and internal reliability are very good. Inter-parental concordance in scoring the child's sleep problem does show differences in the ways in which parents report their children's sleep patterns. Cut-off was calculated for the total score (45). This study validated a 25-item French version of the questionnaire. The French SDSC could therefore be used to aid screening of sleep disorders in the general population.


The Vertebrate Tooth Row: Is It Initiated by a Single Organizing Tooth?
Teeth are one of the most fascinating innovations of vertebrates. Their diversity of shape, size, location, and number in vertebrates is astonishing. If the molecular mechanisms underlying the morphogenesis of individual teeth are now relatively well understood, thanks to the detailed experimental work that has been performed in model organisms (mainly mouse and zebrafish), the mechanisms that control the organization of the dentition are still a mystery. Mammals display simplified dentitions when compared to other vertebrates with only a single tooth row positioned in the anterior part of the mouth, whereas other vertebrates exhibit tooth rows in many locations. As proposed 60 years ago, tooth rows can be formed sequentially from an initiator tooth. Recent results in zebrafish have now largely confirmed this hypothesis. Here this observation is generalized upon and it is suggested that in most vertebrates tooth rows could form sequentially from a single initiator tooth.


Percutaneous CT scan-guided drainage vs. antibiotherapy alone for Hinchey II diverticulitis: a case-control study.
CT-scan-guided percutaneous abscess drainage of Hinchey Stage II diverticulitis is considered the best initial approach to treat conservatively the abscess and to subsequently perform an elective sigmoidectomy. However, drainage is not always technically feasible, may expose the patient to additional morbidity, and has not been critically evaluated in this indication. This study was undertaken to compare the results of percutaneous drainage vs. antibiotic therapy alone in patients with Hinchey II diverticulitis. This was a case-control study of all patients who presented in our institution with Hinchey Stage II diverticulitis between 1993 and 2005. Thirty-four patients underwent abscess drainage under CT-scan guidance (Group 1), and 32 patients were treated with antibiotic therapy alone (Group 2), in most cases because CT-scan-guided abscess drainage was considered technically unfeasible by the interventional radiology team. Initial conservative treatment was considered a failure when: 1) emergency surgery had to be performed, 2) signs of worsening sepsis developed, and 3) abscess recurred within four weeks of drainage. The median size of abscess was 6 (range, 3-18) cm in Group 1 and 4 (range, 3-10) cm in Group 2 (P = 0.002). Median duration of drainage was 8 (range, 1-18) days. Conservative treatment failed in 11 patients (33 percent) of Group 1, and in 6 patients (19 percent) of Group 2 (P = 0.26). Ten patients (29 percent) in Group 1 and five patients (16 percent) in Group 2 underwent emergency surgery (P = 0.24); there were four postoperative deaths (26.6 percent) in this subgroup. Twelve patients (35 percent) in Group 1 and 16 patients (50 percent) in Group 2 subsequently underwent an elective sigmoid resection (P = 0.31). In this subgroup of patients, there was neither anastomotic leakage nor postoperative death. Emergency surgery for Hinchey Stage II diverticulitis carries a high mortality rate and should be avoided. To achieve this, antibiotic therapy alone seems to be a safe alternative, whenever percutaneous drainage is technically difficult or hazardous. Actually, our data did not demonstrate any benefit of CT scan-guided percutaneous abscess drainage, suggesting that the role of interventional radiology techniques in this indication deserves further critical evaluation.


[Ambulatory parenteral antimicrobial therapies. Five-year experience].
INTRODUCTION. To report the five-year experience in ambulatory parenteral antimicrobial treatments of a Hospital at Home (HH). METHODS. Prospective, descriptive study in which demographic data, infection types, antibiotics, dosages, treatment duration, administration methods, and complications were recorded. RESULTS. A total of 325 ambulatory parenteral antibiotic treatments were instituted. The mean age of patients was 56 years (range: 4-96). Patients included 225 men and 100 women. The mean duration of treatment was 16 days (range: 1-176 days). The total number of stays was 4,313 days. The sources of the treated infections included: respiratory tract, 40.3%; osteoarticular, 13.2%; digestive tract, 7%; cytomegalovirus, 6.4%; soft tissue, 5.5%; bacteremias, 5,2%; central nervous system, 4.9%; urinary tract, 4.6%; febrile syndromes, 3.7%; postsurgical, 3%; and endocarditis, 2.5%. Ceftriaxone was the antibiotic most widely used. Seventy-nine percent of treatments were throught the intravenous route. In the last two years infusion pumps were used. Treatment was completed in 93.3% of cases, three patients died and 19 patients required readmission. The most common complication was phlebitis, in 12.6% of cases. CONCLUSIONS. Currently, there is the possibility of safely treating a large number of infections at patient's home with parenteral antibiotics.


Is levoglucosan a suitable quantitative tracer for wood burning? Comparison with receptor modeling on trace elements in Lycksele, Sweden.
Particle emissions from residential wood combustion in small communities in Northern Sweden can sometimes increase the ambient particle concentrations to levels comparable to densely trafficked streets in the center of large cities. The reason for this is the combination of increased need for domestic heating during periods of low temperatures, leading to higher emission rates, and stable meteorological conditions. In this work, the authors compare two different approaches to quantify the wood combustion contribution to fine particles in Northern Sweden: a multivariate source-receptor analysis on inorganic compounds followed by multiple linear regression (MLR) of fine particle concentrations and levoglucosan used as a tracer. From the receptor model, it can be seen that residential wood combustion corresponds with 70% of modeled particle mass. Smaller contributions are also seen from local nonexhaust traffic particles, road dust, and brake wear (each contributing 14%). Of the mass, 1.5% is explained by long-distance transported particles, and 2% derives from a regional source deriving from either oil combustion or smelter activities. In samples collected in ambient air, a significant linear correlation was found between wood burning particles and levoglucosan. The levoglucosan fraction in the ambient fine particulate matter attributed to wood burning according to the multivariate analysis ranged from < 2% to 50%. This is much higher than the fraction found in the emission from the boilers expected to be responsible for most emissions at this site (between 3% and 6%). A laboratory emission study of wood and pellet boilers gave 0.3% wt to 22% wt levoglucosan to particle mass, indicating that the levoglucosan fraction may be highly dependent on combustion conditions, making it uncertain to use it as a quantitative tracer under real-world burning conditions. Thus, quantitative estimates of wood burning contributions will be very uncertain using solely levoglucosan as a tracer.


Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network.
Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR's discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them.


An increase in laryngeal aerosol deposition by ultrasonic nebulizer therapy with intermittent vocalization.
In acute or chronic laryngitis as well as pharyngitis, nebulization with steroid and antibiotics is considered to be a safe and effective treatment. However, the optimal dose, frequency, duration, and method of administration by ultrasonic nebulization is not known. To evaluate whether there is continual improvement using ultrasonic nebulizer therapy, the deposition rate of aerosol particles into the upper airway was studied. We analyzed the deposition rate in the upper airway by a counting system of radioactive isotope (99mTc-diethylene triaminepentaacetic acid; 99mTc DTPA). Volunteers in good health inhaled an aerosol containing 99mTc DTPA under various conditions of inhalation. Deep and slow inhalation at a respiratory rate of 12 breaths/minute resulted in a high deposition rate of 99mTc DTPA in the lung and a low deposition rate in the larynx. In contrast, faster inhalation at a respiratory rate of 36 breaths/minute resulted in an increase in the isotope deposition rate in the larynx. Furthermore, when the volunteers vocalized intermittently during the fast inhalation at a respiratory rate of 36 breaths/minute, the isotope deposition rate in the volunteer's larynx was higher than in all other inhalation conditions. These results suggest that fast inhalation with intermittent vocalization is one of the important inhalation methods used to improve the deposition rate of aerosol particles into the upper airway with an ultrasonic nebulizer.


Induction of maturation in Xenopus laevis oocytes by a steroid linked to a polymer.
A progesterone analog has been covalently linked via an amide bond to polyethylene oxide (molecular weight, 20,000). This macromolecular steroid molecule displays the biological activity of progesterone in inducing meiotic maturation when incubated with Xenopus laevis oocytes (stage VI) in vitro. Its efficiency (half-maximum effective concentration, 30 muM) is approximately 10 times lower than that of its low molecular weight homolog (3 muM). Control experiments with polyethylene oxide and an estradiol derivative (up to 1 mM) assessed the specificity of the progesterone macromolecular analog. Uptake experiments using radioactive derivatives revealed a small (if not negligible) intake of the macromolecular progesterone analog by the oocytes compared to that of free steroids, and no parallelism was found between radioactivity incorporation and effect. The possibility of cleavage of the macromolecular derivative during the incubation was ruled out. Furthermore, injection of the polymer-linked progesterone into the oocytes did not induce maturation. These observations suggest that the macromolecular progesterone analog itself is responsible for the biological effect and that the presence of this compound inside the cell is neither necessary nor sufficient for triggering reinitiation of meiosis. These conclusions are in agreement with the proposal that interaction with the plasma membrane of the oocyte is necessary for progesterone action in this particular system, in contrast to the case of somatic cells which have intracellular steroid receptors.


Uptake of an Acrochordon Incidentally Detected on 68Ga Prostate-Specific Membrane Antigen PET/CT.
Ga prostate-specific membrane antigen (PSMA) PET/CT is a promising tool for imaging of prostate cancer. Ga-PSMA PET/CT uptake of prostate cancer and its metastases are reflective of significant overexpression of PSMA. However, PSMA expression of benign neoplasms and nonprostate epithelial malignancies is not very well defined. We report a moderate Ga-PSMA uptake of an acrochordon (skin tag), which was incidentally found in a patient referred for staging prostate cancer. Acrochordon is a frequent, small, soft, skin-colored or hyperpigmented, benign, and usually pedunculated neoplasm of the skin. Nuclear medicine physicians should be aware of it while reporting a Ga-PSMA PET/CT.


The Effect of Ball Burnishing on Tribological Performance of 42CrMo4 Steel under Dry Sliding Conditions.
Ball burnishing appears to be a very promising approach for reducing surface height, generating compressive residual stresses and increasing hardness. Ball burnishing treatment was carried out using a Haas CNC Vertical Mill Center VF-1 equipped with the Ecoroll burnishing system. After burnishing, surface topographies of machined samples and hardness were measured. Wear tests were conducted using a ball-on-disc tribotester in dry sliding conditions. During tests, the friction force was monitored as a function of time. After tests, wear volumes were determined on the basis of surface texture measurements. Tests revealed that ball burnishing in most cases resulted in minimizing friction and wear of contacting elements.


Mucosa-Associated Ileal Microbiota in New-Onset Pediatric Crohn's Disease.
The composition of the intestinal microbiome seems relevant to the pathogenesis of Crohn's disease (CD), with differences in both diversity and composition of the gut microbiota in patients with CD compared with healthy individuals. However, there are still conflicting reports on the importance of various bacterial taxa in the pathogenesis of CD. The aim of this study was to characterize the composition of mucosa-associated intestinal microbiota in newly diagnosed pediatric patients with CD. Mucosa-associated bacteria were identified from ileal biopsy specimens obtained at colonoscopy of 10 patients with either ileal or ileocolonic new-onset CD and 15 controls without mucosal inflammation. Microbial composition was performed by profiling the 16S rDNA V6 region using Illumina sequencing. Samples were analyzed for differences in alpha/beta diversity and also for differentially abundant taxa. Alpha diversity did not differ between the controls and CD cases or between CD subjects with localized ileal disease compared with those with more extensive disease. Controls also did not clearly separate from patients with CD by principal coordinate analyses; however, 117 operational taxonomic units were found to be differentially abundant between the two groups. In particular, numerous operational taxonomic units associated with Faecalibacterium prausnitzii species were increased in children with CD. These findings contribute to emerging evidence regarding dysbiosis in pediatric CD, and provide additional evidence challenging the protective role of F. prausnitzii in CD.


The patient-centered outcomes research institute: research done differently.
The Patient-Centered Outcomes Research Institute (PCORI) was authorized by the Patient Protection and Affordable Care Act of 2010 to fund comparative clinical effectiveness research to provide reliable evidence to help patients and their healthcare providers make informed decisions. The aim of this paper is to describe the synergy between nursing research and PCORI funding priorities, discuss unique aspects of PCORI funding, and identify the implications for nurse researchers. Goals of nursing research are well aligned with PCORI interests. Given this synergy, many phenomena that nursing scientists study could become topics of a competitive proposal for PCORI funding. Major aspects of PCORI funding with implications for nurse researchers include the nature of the questions asked, funding priorities, engagement of patients and stakeholders, compliance with the PCORI's methodology standards, and the proposal review criteria and process.


Physical activity, age, and arthritis: exploring the relationships of major risk factors on biopsychosocial symptomology and disease status.
The prevalence of arthritis in aging populations continues to rapidly grow. Research has highlighted 2 principal risk factors for progression of arthritis-related biopsychosocial symptoms: age and physical inactivity. This study examined the relationship between and within physical activity and age on biopsychosocial symptoms of arthritis in adults (age ≥ 30 yr). Hierarchical, multiple-regression analyses were conducted on the Canadian Community Health Survey (Cycle 4.2, 2009-2010, N = 19,103). Results revealed that more-active adults had significantly fewer symptoms (physical unstd. B = -.23, p ≤ .001; pyschosocial unstd. B = -.51, p ≤ .001). In addition, as age increased, physical symptoms intensified and psychosocial symptoms tapered (physical unstd. B = .24, p ≤ .001; psychosocial unstd. B = -.45, p ≤ .001). Inactive older adults had the highest level of physical symptoms, while inactive younger adults had the highest level of psychosocial symptoms (p ≤ .001). Findings highlight the need to target physical activity interventions to specific age cohorts and particular biopsychosocial symptomologies.


Exploring the landscape of synthetic IL-6-type cytokines.
Interleukin-6 (IL-6)-type cytokines not only have key immunomodulatory functions that affect the pathogenesis of diseases such as autoimmune diseases, chronic inflammatory conditions, and cancer, but also fulfill important homeostatic tasks. Even though the pro-inflammatory arm has hindered the development of therapeutics based on natural-like IL-6-type cytokines to date, current synthetic trends might pave the way to overcome these limitations and eventually lead to immune-inert designer cytokines to aid type 2 diabetes and brain injuries. Those synthetic biology approaches include mutations, fusion proteins, and inter-cytokine swapping, and resulted in IL-6-type cytokines with altered receptor affinities, extended target cell profiles, and targeting of non-natural cytokine receptor complexes. Here, we survey synthetic cytokine developments within the IL-6-type cytokine family and discuss potential clinical applications.


Identification of lncRNAs by microarray analysis reveals the potential role of lncRNAs in cervical cancer pathogenesis.
Long non-coding RNAs (lncRNAs) have been acknowledged to serve a significant role in cancer biology and abnormal expression in tumors is frequently observed. However, their mechanisms in cervical cancer remain unclear. With a genome-wide analysis of lncRNA expression in cervical cancer tissues, the present study aimed to identify lncRNA targets for the further study of cervical cancer. To elucidate the specific role of lncRNAs in the pathogenesis of this type of cancer, 6 cervical cancer samples paired with normal cervical tissues were obtained. Expression profiles of lncRNAs and mRNAs were constructed through microarray analysis and confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methods. Gene Ontology and pathway enrichment analyses were performed with computational methods. On the basis of correlations between the differential expression levels of lncRNAs and mRNAs, a coding-non-coding gene co-expression network (CNC network) was established. The differential expression of 5,844 lncRNAs and 4,436 mRNAs were discovered in cervical cancer samples compared with normal cervical tissues. Among the differentially expressed lncRNAs, 14 were chosen at random and validated by RT-qPCR; the majority of the results measured were consistent with the microarray results. Furthermore, the lncRNA ENST00000551152 was found to be upregulated and TCO. NS_00001368 lncRNA was downregulated in cervical cancer cell lines. The CNC network included 592 network nodes and 934 associations between 12 lncRNAs and 580 protein-coding genes, indicating that one lncRNA could act on a maximum of 141 coding genes, and that one coding gene may corresponded with a maximum of 5 lncRNAs. Overall, the present study has provided a complete expression profile of lncRNAs and mRNAs in cervical cancer, which may now be used to establish a solid foundation for cervical cancer research. These results may provide significant information for improving the understanding of the pathogenesis of cervical cancer and indicate potential therapeutic targets.


Is the CD14 C159T polymorphism effective in the development of secondary amyloidosis in Familial Mediterranean fever?
The most important complication of FMF is the development of amyloidosis. It is more common in the eastern Mediterranean compared to the US. The individual response to endotoxin may have a significant effect on the development of amyloidosis in FMF patients. To investigate the association between CD14 promotor C-159T polymorphism and development of amyloidosis, one hundred and forty-six patients who had FMF and had not developed amyloidosis; 26 with FMF and secondary amyloidosis and 92 controls were genotyped at the CD14-C159T locus. There was no difference between the genotype distribution of FMF patients (CC 30.0%, CT 50.0%, TT 20.0%) and controls (CC 29.2%, CT 45.8%, TT 25%); or between FMF patients with amyloidosis (CC 30.8%, CT 53.8%, TT 15.4%) or without amyloidosis (CC 29.2%, CT 45.8%, TT 25%). Our study shows that the CD14-C159T polymorphism is not associated with FMF or development of amyloidosis in the population studied. The effect of the genetic variations in the endotoxin signaling pathway under different environmental conditions such as high and low endotoxin exposure remain to be determined.


Many College Students Underestimate Diabetes Risk.
College students form long-lasting diet and health behaviors that are associated with an increased lifetime risk of type 2 diabetes. Thus, colleges and universities can be critical settings to increase awareness of diabetes risk and for nutrition education and health interventions. However, it is not clear if high-risk students recognize the likelihood of diabetes in their future. To assess personal risk perceptions of a sample of multiracial college students with three or more known risk factors for diabetes, and to identity characteristics of students with an unrealistic perception of their future risk. Self-reported data on health and behavior were collected from 1,579 students from three urban colleges. The students at high risk (n=541) for diabetes were categorized as having either a realistic or unrealistic perception of their future risk of diabetes. Characteristics of the two groups were examined using multivariate logistic regression. Approximately 61% of the high-risk students recognized they were more likely to develop diabetes than others, while the remaining 39% did not perceive their personal risk to be high. The under-estimators were significantly more likely to be male (p=0.010), have no family history of diabetes (p=0.029), and be born outside the United States (p<0.001). The under-estimators, an unrealistically optimistic high-risk group, warrant attention, as an unrealistic perception may reduce their likelihood of taking preventive actions to diminish the threat. There is a pressing need to heighten knowledge and awareness of diabetes risk and to develop models of health education and behavior change that are both relevant and effective for young adults.


A comparison of three different scales for rating contact lens handling.
To compare the validity, responsiveness, and reliability of three subjective rating scales applied to soft contact lens (SCL) handling. Fifty-four adapted SCL wearers handled three different types of lenses on two occasions and rated the handling with each scale: visual analogue scales (VAS), 20-interval visual analogue scales with descriptors (VAD) and Likert rating scales with five intervals (LRS). There were significant differences between the scales (p < 0.01) and between the subjective ratings of lens handling (p < 0.001). VAS showed the least variability, exhibited the highest construct validity, were the most responsive, and were the most reliable: interclass correlations (0.63), coefficient of repeatability (27.5), and correlation between test and retest (Spearman r = 0.65, [all p < 0.05]). Higher repeatability, because of the fewer intervals of LRS, was not demonstrated and, generally, LRS was the least satisfactory scale. Handling was rated as easiest using VAD and most difficult using LRS. Although all three scales can be used to provide measures of lens handling, VAS may provide a simple and repeatable tool for measuring subjective responses.


Inhibition of cyclic AMP accumulation in dog heart washed particle preparations by aprotinine.
The effect of aprotinine, a natural non-specific protease inhibitor, on cyclic AMP accumulation in a dog heart washed particle preparation was studied. Aprotinine inhibited GTP-stimulated cyclic AMP accumulation at concentrations equal to or higher than 40 KIU/ml (8 x 10(-7) M). Aprotinine inhibited epinephrine (10(-4) M)-stimulated cyclic AMP accumulation to a greater degree than fluoride (10(-2) M)-stimulated activity. Trypsin stimulated cyclic AMP accumulation at low concentrations (0.5 to 2.5 microgram/ml) and inhibited at higher concentrations. Aprotinine at low concentrations (4 KIU/ml) inhibited the trypsin (1 microgram/ml) stimulation of cyclic AMP accumulation. We conclude that aprotinine may act on the regulator rather than on the catalytic sub-unit of adenylate cyclase and that its mechanism of action is not due only to its antiprotease activity.


Genetic Dissection of Heritable Traits in Yeast Using Bulk Segregant Analysis.
Bulk segregant analysis (BSA) is commonly used to determine the genetic basis of complex traits in yeast. This technique involves phenotyping progeny from a cross and then selectively genotyping pooled subsets of offspring with extreme phenotypes. Analysis of these genotype data can identify loci that show skewed allele frequencies in a group of phenotypically extreme individuals and that are likely to contribute to a trait. BSA can be applied to diverse strain crosses, including ones involving nonreference isolates. Further, given the high throughput of next-generation sequencing, it is possible to conduct many BSA experiments in parallel. Here, we present a BSA protocol for the generation of recombinant cross progeny. We then describe general BSA strategies for conducting phenotyping, causal loci detection, and candidate gene identification in a statistically powerful manner.


120 Hz oscillations in the flash visual evoked potential are strictly phase-locked and limited to the first 100 ms.
Flash stimulation elicits a visual evoked potential (VEP) as part of the electroencephalogram (EEG). This VEP is known to contain strong oscillatory activity around 120 Hz, which ceases 100 ms after the flash. It was unclear so far whether this time limit represents an averaging artifact due to loss of intertrial phase coherence or indicates a veridical cessation. Here we present results obtained from single-trial analysis of the EEG. These show that the oscillations exhibit virtually perfect phase locking and do in fact cease around 100 ms after the stimulus. Thus, the cessation of oscillatory activity in the VEP is not due to increasing intertrial phase jitter. Comparison with simultaneous retinal recordings exclude the possibility of direct crosstalk from the retina, but suggest that the oscillations are propagated from the retina to the cortex with a time lag of 48 ms.


Can anxiety-like behavior and spatial memory predict the extremes of skilled walking performance in mice? An exploratory, preliminary study.
Skilled walking is influenced by memory, stress, and anxiety. While this is evident in cases of neurological disorders, memory, and anxiety traits may predict skilled walking performance even in normal functioning. Here, we address whether spatial memory and anxiety-like behavior can predict skilled walking performance in mice. A cohort of 60 adult mice underwent a behavioral assessment including general exploration (open field), anxiety-like behavior (elevated plus maze), working and spatial memory (Y-maze and Barnes maze), and skilled walking performance (ladder walking test). Three groups were established based on their skilled walking performance: superior (SP, percentiles ≥75), regular (RP, percentiles 74-26), and inferior (IP, percentiles ≤25) performers. Animals from the SP and IP groups spent more time in the elevated plus maze closed arms compared to the RP group. With every second spent in the elevated plus maze closed arms, the probability of the animal exhibiting extreme percentiles in the ladder walking test increased by 1.4%. Moreover, animals that spent 219 s (73% of the total time of the test) or more in those arms were 4.67 times more likely to exhibit either higher or lower percentiles of skilled walking performance. We discuss and conclude anxiety traits may influence skilled walking performance in facility-reared mice.


Evidence that growth hormone exerts a feedback effect on stomach ghrelin production and secretion.
Ghrelin is a recently discovered stomach hormone that stimulates pituitary growth hormone (GH) secretion potently. The purpose of these experiments was to test the hypothesis that a stomach-ghrelin-pituitary-GH axis exists in which either an elevation or reduction in systemic GH levels will exert a negative or positive feedback action, respectively, on stomach ghrelin homeostasis. In rats, GH administration decreased stomach ghrelin mRNA levels and plasma ghrelin levels significantly. In GH-releasing hormone (GHRH) transgenic mice, GHRH overexpression decreased stomach ghrelin peptide levels when compared with control mice. In aged rats (25 months) stomach ghrelin mRNA and peptide levels and plasma ghrelin levels were decreased when compared with young rats (5 months). Because GH secretion is reduced in aged rats, the elevated stomach ghrelin production and secretion may reflect a decreased GH feedback on stomach ghrelin, homeostasis, and secretion. Together, these findings suggest that endogenous pituitary GH exerts a feedback action on stomach ghrelin homeostasis and support the hypothesis that a stomach-ghrelin-pituitary GH axis exists.


Extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines treats vulvovaginal candidiasis by affecting the vaginal mucosal barrier.
Aim: This study investigated the inhibition of extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines (ESCC) on Candida albicans (C. albicans) in vitro and the effect of ESCC on the vaginal mucosal barrier in vivo. Materials & methods: Susceptibility testing was performed with C. albicans SC5314. A vulvovaginal candidiasis mouse model was successfully established. The plate method, Gram staining, hematoxylin and eosin staining and ELISA were used to detect relevant inflammatory indexes: IFN-γ, IL-1 and TNF-α. Quantitative real-time PCR and western blot were used to detect mucosal immune-related factors: MUC1, MUC4, DEFB1 and DEFB2. Results: ESCC was able to inhibit the proliferative activity of C. albicans, and it affected inflammation-related factors and indicators of vaginal mucosal immunity. Conclusion: ESCC showed potential value in the treatment of vulvovaginal candidiasis.


Assessment of capacity for medical decision making.
Determination of a patient's capacity for medical decision making can be simple or complex, depending on the issue being considered; likewise, the degree of capacity required to make decisions varies with the complexity of the situation. A capacity examination is a focused and impartial evaluation of mental status and medical, surgical, psychiatric, and psychosocial histories. The examination is composed of several basic steps, beginning with an assessment of the patient's ability to communicate, followed by determination of his or her understanding of the proposed care, followed by the patient's rationale for decisions about that care. When a patient is deemed to lack capacity, mechanisms should be in place to ensure the patient receives the care needed. This article provides an overview of the concept of capacity, how it is determined, and how to proceed when the patient is found to lack it.


Income distribution in rural Sagar.
"The study makes an attempt to identify the pattern of household income distribution in rural areas, based on the socio-economic surveys in Sagar district [in India]." Factors affecting family income include "occupational structure, distance from nearby urban centers and general accessibility.... The rural settlements under urban influence or with proper accessibility have a greater percentage of high-income families. The major source of income for over a third of the rural families of the district is agricultural labour, while another third earns its living by other agricultural work and the rest are either petty businessmen or are engaged in services."


[Surgical treatment of postintubation stenosis of the larynx in children].
Post-intubation laryngeal stenosis is the most common cause of upper respiratory obstruction in children. According to published data, the incidence of post-intubation stenosis ranges from 0.1 to 20%. Treatment of children with chronic laryngeal stenosis is a special branch of respiratory surgery. It remains one of the most complex and urgent problems in pediatrics, pediatric otorhinolaryngology, and pediatric surgery. Although numerous studies have described various methods for treating stenosis of the infraglottic space, there is no standard management approach. Currently, there are two main treatment methods: endoscopic interventions and open reconstructive surgery. Each method has its benefits and drawbacks. Despite the use of various techniques, the effectiveness of cicatricial laryngeal stenosis repair and decannulation in children is 63-64%, according to published data. With combined lesions of infraglottic and vocal cord parts of the larynx, especially with their cicatricial obliteration, reconstructive surgery is successful only in 50% of cases. Thus, treating children with post-intubation respiratory stenosis remains a complex problem and is a relevant direction for further research.


Structural characterization of a dynein motor domain.
Cytoplasmic dynein is a microtubule-based mechanochemical protein that plays an essential role in cell division, vesicle transport, and cytoplasmic membrane organization. As a molecular motor, dynein utilizes an ATP hydrolysis mechanism to bind and release microtubules and to undergo conformational changes that result in a net displacement towards the microtubule's minus end. To visualize structural features of this motor protein, we have begun to characterize the dynein head domain by electron microscopy and image processing. Transmission electron microscopy of negatively stained native dynein from Dictyostelium has been performed and images of the head domain have been aligned and analyzed with the software SPIDER. The resulting 2D averages show an oblong round shape composed of seven to eight globular domains or lobes that encircle a stain-filled area. A recombinant 380 kDa fragment of the dynein heavy chain encodes just the globular head domain; analysis of these particles reveals a high structural similarity with the native head domain. A prominent stalk can be seen in several projections of this fragment, suggesting a structure analogous to the B-link described for some axonemal dyneins. Single tilt pair images were used to compute low resolution 3D reconstructions of the dynein head domain. These show a flattened spheroidal shape of 13.5 nm in length with seven similar domains arranged in a ring. Slices through the reconstructions reveal a large central cavity. This is the first detailed description of the head domain structure for a dynein molecule. The presence of a central cavity and the outer globular features, along with its large size make dynein structurally distinct from either myosin or kinesin.


Developing perennial wildflower strips for use in Mediterranean orchard systems.
To support sustainable food production and the delivery of ecosystem services through ecological intensification, wildflower strips have become a popular strategy. Despite their success in temperate orchard systems, they remain understudied in Mediterranean ecosystems, which poses a significant barrier to uptake. In order to further promote their adoption, seed mixes must be optimised for commercial orchard systems and for the Mediterranean climate. Plant species should be selected for their consistent performance, whilst the availability of resources for ecosystem service providers determines the quality of the wildflower strip. In this study, the suitability of 12 native perennial forbs and two tussock-forming grass species for wildflower strips in commercial Citrus orchards was assessed over a 3-year period. Distinct resources for natural enemies according to the different plant growth stages were used an indicator of wildflower strip quality. The wildflower strips were managed under two different cutting strategies: (i) standard management, in which wildflower strips were cut once annually in February, and (ii) active management, in which wildflower strips were cut two additional times each year. The establishment and success of the sown species were compared. The influence of wildflower strips and their management on plant species richness, community structure, and the provision of resources was compared with a control treatment, in which alleyways were managed conventionally by cutting any naturally occurring vegetation to a height of ≤5 cm, four to five times annual. For the first time, the performance of native perennial plant species has been assessed in Mediterranean orchard systems and a seed mix developed for targeting pest regulation services. The wildflower strips were successful in increasing plant species richness and the available resources expected to support natural enemies. However, only wildflower strips managed with cutting once annually enhanced vegetation cover relative to the control, whilst extending the flowering period. This study therefore provides crucial tools for the further development of sustainable approaches to food production in Mediterranean orchard systems.


Serial PET studies of human cerebral malignancy with [1-11C]putrescine and [1-11C]2-deoxy-D-glucose.
Serial PET measurements of [1-11C]putrescine ([11C]PUT) uptake and glucose metabolic rate (GMR) using [1-11C]2-deoxy-D-glucose ([11C]2DG) were made on eight human subjects with a radiological and, in most cases, pathological diagnosis of primary or metastatic brain tumor. Blood-to-brain influx constants (Ki) were calculated for [11C]PUT. Tumor uptake of 11C after [11C]PUT injection was unidirectional peaking at 15 min. The mean +/- s.d. Kis for [11C]PUT for tumor and normal brain tissue were 0.78 +/- 0.045 and 0.024 +/- 0.007 ml cc-1 min-1, respectively (average of ratio, 3.11) whereas the ratio of GMR for tumor and normal brain tissue was 1.2 +/- 0.5. The mean Ki for four active, high grade astrocytomas was 0.098 +/- 0.030 in contrast to 0.027 +/- 0.008 ml cc-1 min-1 for two patients with low grade astrocytoma. Active high grade astrocytomas also showed marked CT contrast enhancement and regional glucose hypermetabolism. In one subject with brain metastases, both [11C]PUT and GMR correlated with a declining clinical picture in repeated studies over a 4-mo period. PET studies with [11C]PUT provide a better signal:noise ratio than GMR measurements, are useful for locating small glycolytically hypometabolic tumors and, when used in longitudinal studies in a single subject, appear to provide an index of degree of malignancy.


[Tuberculosis morbidity among military personnel in modern conditions].
Among identified in the army for one year of active tuberculosis patients constitute 38.7% of the number of soldiers from young recruits, including 59.7% of infiltrative pulmonary tuberculosis. At the same time during the examination of these individuals revealed only about half of patients. Timely delivery of fluorographic examination recruitment plays a crucial role in preventing the spread of tuberculosis in the Armed Forces. From the military doctors need more work in groups at increased risk of tuberculosis, early identification of need in the dispensary dynamic observation and conducting a full range of therapeutic and preventive measures in foci of tuberculous infection.


[Concomitant urogenital infections in men].
The article presents possible combinations of urogenital infections of various etiologies and some pathogenetic, clinical and epidemiological features, and issues of epidemiological surveillance for co-infection. The authors describe in detail combinations with each other and with other diseases of such pathogens as Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma spp., Neisseria gonorrhoeae, Trichomonas vaginalis. They also focus on the problem of co-occurrence of human papillomavirus (HPV) with other urogenital pathogens. The article raises the question of the need to introduce new scientific data on the epidemiology of concomitant urogenital infections in men in the practice of diagnosis, treatment, registration, and implementation of preventive and anti-epidemic measures.