Psychopathology of obsessive-compulsive disorder: a phenomenological approach.
Until the beginning of the 20th century, the idea of obsession found in the literature was mostly a broad and unspecific one, and it has, to some extent, persisted in this form until the present day. At the same time, however, Esquirol and Westphal began to develop a concept of obsession in the strict sense, and Jaspers used the phenomenological method as a basis to give it its final form. The concept of obsession in the strict sense represents the formal and nosologically specific core symptom of obsessive-compulsive disorder. In conjunction with the distinction between primary and secondary obsessions, obsession in the strict sense is proving helpful in differential diagnosis, but it can also serve as a guideline in the further phenomenological investigation of obsessive-compulsive disorder. It is shown how the interaction between personality, affect and release situation develops the obsessive-compulsive disorder. The clarification of these aspects with the patient can at the same time be the starting point of psychotherapeutic treatment.


[Clincio-electroencephalographic syndromes in several diseases of the nervous system].
An analysis of the indices of bioelectrical brain activity and clinical symptoms was accomplished by a computer according to the principle "man-machine". The authors examined 2 groups of patients with some hereditary forms of diseases of the nervous system (62 cases) and with disorders of cerebral circulation (106 cases). It was demonstrated that there is a possibility of clarifying the typical localization of lesion and of differentiating the different clinico EEG syndromes.


Can correcting the ΔF508-CFTR proteostasis-defect rescue CF lung disease?
Protein homeostasis (proteostasis) generates and maintains individual proteins in their folded and functional-competent states. The components of the cellular proteostasis machinery also dictate the functional lifetime of a protein by constantly regulating its conformation, concentration and subcellular location. The autosomal recessive disease cystic fibrosis (CF) is caused by a proteostasis-defect in CF transmembrane conductance regulator (CFTR). The most common CF mutation leading to this proteostasis-defect is the deletion of a phenylalanine residue at position 508 (ΔF508) of the CFTR protein. This ΔF508-CFTR protein is prone to aberrant folding, increased ER-associated degradation, atypical intracellular trafficking and reduced stability at the apical membrane. This ΔF508-CF proteostasis-defect leads to an obstructive lung disease characterized by impaired ion transport in airway epithelial cells, mucus buildup in air space and chronic airway inflammation. We assess here whether correcting the underlying defect in ΔF508-CFTR protein processing using therapeutic proteostasis regulators can treat chronic CF lung disease. As a proof of concept, recent studies support that the selective modulation of mutant-CFTR proteostasis may offer promising therapies to reverse chronic CF lung disease.


[Experimental and clinical study of d, 1-oxyphedrin].
Comparative pharmacological and toxicological studies were carried out on animals covering the preparation d,1-oxyphedrine (myophedrine), put out in the GDR, as against the drug 1-oxyphedrine. The activity of both drugs showed no material difference. Clinical trials demonstrated good tolerance of the drug both by healthy persons and patients with its intravenous administration twice a day in amounts of 1 mg, or by mouth--3 times a day in amounts of 8--16 mg. In outpatients with anginal pains after sustained myocardial infarction and also in institutionally treated patients with myocardial infarction the activity of d,1-oxyphedrine proved to be not inferior to that of 1-oxyphedrine.


C6 peptide ELISA test in the serodiagnosis of Lyme borreliosis in Sweden.
The aim of this study was to evaluate the synthetic C6 peptide test as a first-line test in a two-tiered scheme for Borrelia serology in a clinically well-characterized population of patients with Lyme borreliosis in Kalmar County, Sweden. The study population consisted of a prospective group (n = 200), a control group (n = 255), and a retrospective group (n = 29). The test panel consisted of the Immunetics Quick ELISA C6 Borrelia assay kit (Immunetics, Cambridge, MA, USA), the Virotech Borrelia burgdorferi ELISA (Genzyme Virotech, Rüsselsheim, Germany), and the Liaison Borrelia CLIA (DiaSorin, Saluggia, Vercelli, Italy). Seroprevalence among 200 healthy blood donors was significantly lower in the C6 test (8%) compared to the Virotech ELISA (14%) and the Liaison CLIA (12%). In convalescent sera (2-3 months and 6 months post infection) from 158 patients with erythema migrans, the seropositivity in the C6 test was also significantly lower compared to both the Virotech ELISA and the Liaison CLIA. Serosensitivity in the acute phase of erythema migrans and other clinical manifestations of borreliosis did not differ significantly between the C6 test and the Virotech ELISA or the Liaison CLIA. Overall, a positive C6 test seems to correlate well with acute borreliosis. Cross-reactivity was lower in the C6 test in sera positive for Epstein-Barr virus infection as compared to the Virotech ELISA. This study supports the use of the C6 test as a screening test for borreliosis, in endemic areas.


Early comprehensive testing for COVID-19 is essential to protect trauma centers.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presents a threat to health care systems worldwide. Trauma centers may be uniquely impacted, given the need for rapid invasive interventions in severely injured and the growing incidence of community infection. We discuss the impact that SARS-CoV-2 has had in our trauma center and our steps to limit the potential exposures. We performed a retrospective evaluation of the trauma service, from March 16 to 30, following the appearance of SARS-CoV-2 in our state. We recorded the daily number of trauma patients diagnosed with SARS-CoV-2 infection, the presence of clinical symptoms or radiological signs of COVID-19, and the results of verbal symptom screen (for new admissions). The number of trauma activations, admissions, and census, as well as staff exposures and infections, was recorded daily. Over the 14-day evaluation period, we tested 85 trauma patients for SARS-CoV-2 infection, and 21 (25%) were found to be positive. Sixty percent of the patients in the trauma/burn intensive care unit were infected with SARS-CoV-2. Positive verbal screen results, presence of ground glass opacities on admission chest CT, and presence of clinical symptoms were not significantly different in patients with or without SARS-CoV-2 infection (p > 0.05). Many infected patients were without clinical symptoms (9/21, 43%) or radiological signs on admission (18/21, 86%) of COVID-19. Forty-five percent of trauma patients are asymptomatic at the time of SARS-CoV-2 diagnosis. Respiratory symptoms, as well as verbal screening (recent fevers, shortness of breath, cough, international travel, and close contact with known SARS-CoV-2 carriers), are inaccurate in the trauma population. These findings demonstrate the need for comprehensive rapid testing of all trauma patients upon presentation to the trauma bay. Diagnostic tests or criteria, level III, Therapeutic/care management, level IV.


GnRH analogues in the treatment of uterine fibroids.
It is now known that gonadotrophin-releasing hormone analogues (GnRHa) are extremely efficient at reducing uterine fibroid volume and reversing the related symptomatology. However, the fibroids tend to return to their pretreatment size about 6 months after discontinuing treatment. GnRHa treatment cannot be continued indefinitely due to its potential complications and high cost. It is therefore proposed that GnRHa treatment should be phase one of a two-phase treatment plan for uterine fibroids. The initial course of GnRHa should be followed by either menopause or surgery. Experience with presurgical GnRHa use indicates a definite treatment advantage and the use of GnRHa as adjuncts to surgery is well established. The value of GnRHa treatment as a alternative to surgery in pre-menopausal patients, however, remains to be established.


The minimal number of TMS trials required for the reliable assessment of corticospinal excitability, short interval intracortical inhibition, and intracortical facilitation.
Transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) are frequently used to assess corticospinal and intercortical activities. Trial to trial variance of the potentials is commonly observed, and averages of multiple MEPs are usually reported. Multiple trials have resources implications and are not compatible with some experimental protocols. This study investigated the minimum number of MEPs required to reliably assess corticospinal excitability (CSE), short interval intracortical inhibition (SICI) and intercortical facilitation (ICF), within and between sessions. Fifteen healthy volunteers received 35 single-pulse TMS for CSE assessments and 35 paired-pulse TMS for SICI and ICF measurements. Intra- and intersession reliability were examined using intra-class correlation coefficient tests, and stability of the measures was assessed using a general equation estimation analysis. Coefficients of variation were used to probe the effects of inter-individual variability on reliability results. All analyses were carried out on cumulative averages. The optimal number of trials to ensure "excellent" intra and inter-session reliability with low inter-individual variability and the highest level of stability was found to be 20 for CSE and 26 for SICI assessments. Although 30 consecutive trials produced highly reliable ICF measures within a session, inter-session reliability was not significant across 35 trials. These findings have significant implications for improving time efficiency of TMS experiments without compromising intra- or intersession reliability.


External Validation of the International IgA Nephropathy Prediction Tool.
The International IgA Nephropathy Network recently developed and externally validated two models to predict the risk of progression of IgA nephropathy: full models without and with race. This study sought to externally validate the International IgA Nephropathy Prediction Tool in a large, independent, and contemporary cohort in China. We included 1373 patients with biopsy-confirmed primary IgA nephropathy from The First Affiliated Hospital of Zhengzhou University from January 2012 to May 2018 and calculated predicted risks for each patient. The outcomes of interest were a 50% decline in eGFR or kidney failure. We assessed the performance of both models using discrimination (concordance statistics and Kaplan-Meier curves between subgroups), calibration (calibration plots), reclassification (net reclassification improvement and integrated discrimination improvement), and clinical utility (decision curve analysis). The median follow-up was 29 months (interquartile range, 21-43 months; range, 1-95 months), and 186 (14%) patients reached the kidney outcomes of interest. Both models showed excellent discrimination (concordance statistics >0.85 and well separated survival curves). Overall, the full model without race generally underestimated the risk of primary outcome, whereas the full model with race was well calibrated for predicting 5-year risk. Compared with the full model without race, the full model with race had significant improvement in reclassification, as assessed by the net reclassification improvement (0.49; 95% confidence interval, 0.41 to 0.59) and integrated discrimination improvement (0.06; 95% confidence interval, 0.04 to 0.08). Decision curve analysis showed that both full models had a higher net benefit than default strategies, and the model with race performed better. In this study, both full models demonstrated remarkable discrimination, acceptable calibration, and satisfactory clinical utility. The relatively short follow-up time may have limited the validation of these models.


Biomineralization State of Viruses and Their Biological Potential.
In nature, viruses can realize self-mineralization under metal-ion-abundant conditions. Interestingly, the mineralized state is a transition state of the virus when the host is not available. Mammalian viruses that share the similar chemical properties also stand a chance of transformation into a mineralized state. In this review, we focus on the possibility of mammalian viruses to undergo mineralization under a physiological environment and the development of biomineralized-based virus engineering. We will introduce the effect of biomineralization on the physiochemical or biological properties of viruses and we will discuss the relationship between mineral composition and biological potentials. The new biological prospects of mineralized-state viruses, including bypassing biological barriers, protection, and virus-host recognition, will provide new insight for the biosecurity and prevention of viral infection. With respect to vaccines, the mineralized state can modulate the immune recognition, change the immunization route, and elevate the vaccine efficacy. Together, these findings of the mineralized state of the virus may lead to a new understanding of virus biology, application, and prevention.


Molecular biology of the GABA(A) receptor: functional domains implicated by mutational analysis.
GABA(A) receptors are the major inhibitory neurotransmitter receptors in mammalian brain. They belong to a family of ligand-gated ion channels that also includes the nicotinic acetylcholine receptors, glycine receptors and 5HT(3) receptors. Each receptor in the family is believed to be a pentamer of homologous subunits that assemble to form a central transmembrane ion pore which, in the case of the GABA(A) receptor, is anion-selective. For almost twenty years, there has been tremendous interest in the structure and function of GABA(A) receptors, not only because of their importance in regulating brain excitability but also because these proteins are the specific targets for a wide variety of therapeutic agents including the anxiolytic benzodiazepines and barbiturates. Molecular cloning has revealed that GABA(A) receptors are heterogeneous, being formed by combinations of different isoforms of several subunit classes (alpha, beta, gamma, delta). The physiological and pharmacological properties of individual GABAA receptor subtypes appear to depend on their precise subunit complement. In this review, we focus on the application of modern techniques in molecular biology, particularly mutational analysis, to identify structural domains of these receptors that are important for ligand recognition and receptor function.


Toward efficient photomodulation of conjugated polymer emission: optimizing differential energy transfer in azobenzene-substituted PPV derivatives.
We present fluorescence studies of quenching behavior in photoaddressable azobenzene-substituted derivatives of the fluorescent conjugated polymer poly(p-phenylenevinylene) (PPV). The azobenzene side chains partially quench the PPV fluorescence, and we have shown previously that the quenching efficiency is greater when the azobenzene side chains are cis than when they are trans. This effect provides a photoaddressable means of modulating the fluorescence intensity of PPV derivatives. To optimize the efficiency of photoinduced intensity modulation, it is important to understand the molecular nature of quenching by both trans- and cis-azobenzene side chains. Here we investigate the photophysical origins of quenching by the two isomers using steady-state and time-resolved fluorescence spectroscopy. We present results from the azobenzene-modified PPV derivative poly(2-methoxy-5-((10-(4-(phenylazo)phenoxy)decyl)oxy)-1,4-phenylenevinylene) (MPA-10-PPV) and two new related polymers, a copolymer lacking half of the azobenzene side chains and an analogue of MPA-10-PPV with a tert-butyl-substituted azobenzene. These studies reveal that steric interactions influence the extent of PPV emission quenching by trans-azobenzene but do not affect the efficient quenching by cis-azobenzene. The difference in dynamic quenching efficiencies between trans- and cis-azobenzene isomers is consistent with fluorescence resonance energy transfer. These results show that it is possible to control the efficiency of photoswitchable fluorescence modulation through specific structural variations designed to encourage or block quenching by trans-azobenzene. This is a promising approach to providing useful general guidelines for designing photomodulated PPV derivatives.


Bioelectrical impedance vector analysis in obese and overweight children.
BMI is the most commonly used indicator to evaluate overweight and obesity, but it cannot distinguish changes in body composition. Over recent years, it has been demonstrated that bioelectrical impedance analysis (BIA) is a more accurate method for analyzing body composition. Bioelectrical impedance vector analysis (BIVA) has revealed its effectiveness as an indicator of nutritional status and hydration. To assess the usefulness of bioimpedance analysis on the study of body composition in a group of children with overweight and obesity. Cross-sectional observational study. The anthropometric parameters of 167 (79 were older than 12 years) overweight and obese children were recorded. Their body composition was analyzed using BIA and BIVA, and was classified based on different criteria. Concordance was analyzed (intraclass correlation coefficient, Bland-Altman analysis and weighted Kappa coefficient). The BIVA of the subgroups was compared using the Mahalanobis distance and Hotelling's T2. Statistical significance was considered for p<0.05. The BMI revealed that the majority of the assessed subjects were obese, although 12% had a normal percentage of fat mass (%FM). The classification by Z-BMI and Z-%FM significantly discriminate between subjects with different levels of adiposity. In children over the age of 12, the classification of fat mass index also discriminates significantly between obesity and non-obesity. As anticipated, in the tolerance ellipses, most of the individual vectors were situated in the left lower quadrant. BIVA reflects differences in the bioelectric patterns of children who are classified as being overweight or obese (BMI) and who have different levels of %FM and FMI. BIVA permits a fast and easy monitoring of the evolution of the nutritional state and changes associated with body composition, and it identifies those children whose body compartments may be precisely estimated using traditional BIA methods.


Preformation and distribution of staminate and pistillate flowers in growth units of Nothofagus alpina and N. obliqua (Nothofagaceae).
The distribution and differentiation times of flowers in monoecious wind-pollinated plants are fundamental for the understanding of their mating patterns and evolution. Two closely related South American Nothofagus species were compared with regard to the differentiation times and positions of staminate and pistillate flowers along their parent growth units (GUs) by quantitative means. Two samples of GUs that had extended in the 2004-2005 growing season were taken in 2005 and 2006 from trees in the Lanín National Park, Patagonia, Argentina. For the first sample, axillary buds of the parent GUs were dissected and the leaf, bud and flower primordia of these buds were identified. The second sample included all branches derived from the parent GUs in the 2005-2006 growing season. Both species developed flowering GUs with staminate and/or pistillate flowers; GUs with both flower types were the most common. The position of staminate flowers along GUs was similar between species and close to the proximal end of the GUs. Pistillate flowers were developed more distally along the GUs in N. alpina than in N. obliqua. In N. alpina, the nodes bearing staminate and pistillate flowers were separated by one to several nodes with axillary buds, something not observed in N. obliqua. Markovian models supported this between-species difference. Flowering GUs, including all of their leaves and flowers were entirely preformed in the winter buds. Staminate and pistillate flowers of N. alpina and N. obliqua are differentiated at precise locations on GUs in the growing season preceding that of their antheses. The differences between N. alpina and N. obliqua (and other South American Nothofagus species) regarding flower distribution might relate to the time of anthesis of each flower type and, in turn, to the probabilities of self-pollination at the GU level.


Comparison of sister chromatid exchanges in spleen and thymus lymphocytes from AKR, C57BL/6N x DBA/2J F1, and CBA mice following in vivo exposure to N-methyl-N-nitrosourea.
The induction of sister chromatid exchange (SCE) by N-methyl-N-nitrosourea (MNU) was studied in spleen and thymus lymphocytes from AKR mice, which are highly susceptible to MNU-produced thymomas, CBA mice, which are much less sensitive to induction of thymomas by MNU, and C57BL/6N x DBA/2J F1 mice. MNU produced dose-related increases in SCE in concanavalin A (Con A)- and lipopolysaccharide-stimulated spleen lymphocytes and Con A-stimulated thymus lymphocytes from each mouse strain at 1 and 24 h posttreatment. MNU-induced SCE were generally higher in Con A-stimulated spleen lymphocytes compared to lipopolysaccharide-stimulated spleen lymphocytes and Con A-stimulated thymus lymphocytes from each mouse strain. On the whole, MNU-produced SCE were lower in AKR and CBA spleens than in C57BL/6N x DBA/2J F1 spleens. In addition, MNU-induced SCE levels in thymus lymphocytes from all three strains of mice were, for the most part, similar. These results indicate that if differences in MNU-induced genotoxicity in AKR, CBA, and C57BL/6N x DBA/2J F1 thymus lymphocytes exist, these differences cannot be ascertained by use of the in vivo/in vitro SCE assay.


Ischemic stroke following abuse of Marijuana in a Nigerian adult male.
Cannabis is the most widely used illicit drug among adolescents and young adults. Despite its widespread use, only a few reports exist on the association of cannabis use and stroke. A 26-year-old Nigerian male, developed right-sided ischemic stroke few hours after smoking three wraps of cannabis. He had smoked cannabis consistently for the past 4 years prior to the development of the stroke. Known stroke etiology and abuse of other illicit drugs were ruled out from history and investigations. Neuroimaging studies of the brain revealed infarcts in basal ganglia secondary to occlusion of blood flow in the left anterior and middle cerebral arteries. The mechanism of stroke in this patient was thought to be a cannabis-induced vasculopathy. Many cases of stroke in the young are increasingly being seen in hospitals in resource scarce countries. There seems to be a predilection for the basal ganglia in ischemic stroke following cannabis abuse. Therefore, cannabis abuse should be considered in young adults with basal ganglia infarcts, after excluding other known etiologies.


[Structure and immunohistochemistry of the hypophysis of Alosa fallax nilotica during the reproductive migratory cycle].
The Pituitary of the Alosa fallax nilotica consists of a pars distalis, a pars intermedia and a pars nervosa. The pars distalis is divided into rostral and proximal. The pars nervosa extends also into proximal pars distalis. The rostral pars distalis, on the contrary in primitive Teleostei, has organized into cellular cords defining cavities or intercommunicating follicles. These latter finish into the oral adenohypophysial duct, which don't open in pharyngeal cavity. The cords contain three cell types: the columnar cells LTH, TSH cells and basal cells not yet functionally determined. The cord cells are separated from follicle cavity by an one layer of flat degranulated cells. The LTH cell, the chief cell type, together the TSH and basal cells shows evident cytologic differences in organelles of synthesis and secretion during the various stages of the reproductive migration. Besides globular and baton-shape projections are underlined in the apical cytoplasm of LTH cells. These structure, extending into follicle cavity, seem to dispatch sensory function probably. The proximal pars distalis consists of compact cords of gonadotropic cells (particularly active during the stage of migration from rivers to the sea) with inserted orangiophilic cells (probably STH) and phloxine cells: these latter cells are chiefly arranged at the periphery and immunocytochemical positive for the antibodies against ACTH. The pars intermedia contains cord of ACTH cells, particularly manifest during the periods of transit from sea water to fresh water and on the contrary, they are characterized by positive-ACTH dense granules. On the ground of ultrastructural aspects of vesicles, the pars nervosa shows three types of nervous fibers which correlate with neurosecretory hypothalamus and catecholaminergic dopaminergic fibers. The Authors think of underlining particularly that the all cells of rostral pars distalis and chiefly the LTH cells are involved significantly in the regulation of reproduction and hydro-mineral metabolic equilibrium.


Novel viral genomes identified from six metagenomes reveal wide distribution of archaeal viruses and high viral diversity in terrestrial hot springs.
Limited by culture-dependent methods the number of viruses identified from thermophilic Archaea and Bacteria is still very small. In this study we retrieved viral sequences from six hot spring metagenomes isolated worldwide, revealing a wide distribution of four archaeal viral families, Ampullaviridae, Bicaudaviridae, Lipothrixviridae and Rudiviridae. Importantly, we identified 10 complete or near complete viral genomes allowing, for the first time, an assessment of genome conservation and evolution of the Ampullaviridae family as well as Sulfolobus Monocaudavirus 1 (SMV1)-related viruses. Among the novel genomes, one belongs to a putative thermophilic virus infecting the bacterium Hydrogenobaculum, for which no virus has been reported in the literature. Moreover, a high viral diversity was observed in the metagenomes, especially among the Lipothrixviridae, as indicated by the large number of unique contigs and the lack of a completely assembled genome for this family. This is further supported by the large number of novel genes in the complete and partial genomes showing no sequence similarities to public databases. CRISPR analysis revealed hundreds of novel CRISPR loci and thousands of novel CRISPR spacers from each metagenome, reinforcing the notion of high viral diversity in the thermal environment.


A dynamic wicking technique for determining the effective pore radius of pregelatinized starch sheets.
A dynamic wicking technique is employed for the first time for the determination of the effective mean pore radius of a thin-layer porous food: drum dried pregelatinized starch sheets. The technique consists of measuring the penetration rate of various n-alkanes in the porous matrix of the starch sheets and using this data to calculate the effective pore radius via the Washburn equation. Pore sizes in the order of a few nanometers have been determined in the starch sheets depending on the drum dryer's operating variables (drum rotation speed, steam pressure and starch feed concentration). The conditions for the application of the technique in porous foods are discussed as compared to the conditions for single capillaries and inorganic porous material measured in other studies.


Hypertrophic Cardiomyopathy and Sudden Death Initially Identified at Autopsy.
Hypertrophic cardiomyopathy (HC) is associated with a well-recognized risk for unexpected sudden death (SD). Most such reported patients have been referred to dedicated centers and/or expert cardiologists for risk stratification, with the number of SDs decreasing sharply due to penetration of the implantable cardioverter-defibrillator (ICDs) into HC practice. However, the clinical circumstances, and morphologic features of HC patients who incur SD without the opportunity to be considered for preventive intervention with ICDs are largely undefined. Using the long-standing unique Jesse Edwards Registry (St. Paul, Minnesota), we studied 86 selected heart specimens from young HC patients who died suddenly and unexpectedly without prior clinical evaluation, ages 31 ± 16 years. The patients were predominantly male (87%) with only modest phenotypic expression and maximum LV wall thickening of only 18 ± 4 mm. SD events occurred predominantly with sedentary/mild activities (66%) often in bed or asleep (32%), but also during physical activity (22%) including with organized competitive sports. This largely unappreciated sub-population of patients with HC (and SD) is characterized by mild-to-moderate degree of LV hypertrophy, representing a clinical challenge which is particularly relevant in the current ICD era for HC, with the potential for SD prevention.


Which dimensions of impulsivity are related to cigarette craving?
Cigarette smoking is a very important health problem and represents the largest preventable risk factor for premature death in developed countries. A considerable body of research indicates that impulsivity is a central etiological concept in many theoretical models of tobacco addiction. The aim of this study is to analyse which dimensions of impulsivity are related to cigarette craving. To this end, 40 undergraduate psychology students were screened using the revised Questionnaire on Smoking Urges (QSU-12) and the French adaptation of the UPPS Impulsive Behavior Scale (UPPS). This scale identifies four distinct components associated with impulsive behaviour: urgency, lack of premeditation, lack of perseverance, and sensation seeking. The results showed that urgency is a significant predictor of tobacco cravings, while depression and anxiety are not.


Mycolic acid patterns of representative strains of Mycobacterium fortuitum, 'Myobacterium peregrinum' and Mycobacterium smegmatis.
Representative strains of Mycobacterium fortuitum, 'Mycobacterium peregrinum' and Mycobacterium smegmatis were degraded by acid methanolysis and patterns of long-chain compounds were determined by two-dimensional thin-layer chromatography. The same general pattern of mycolic acid methyl esters was found in all 39 strains examined, the major components being so-called alpha-mycolates and characteristic pairs of polar mycolates. Analysis of alkaline methanolysates of selected strains confirmed that these polar mycolates were derived from epoxymycolic acids, as found previously.


Translation initiation in Saccharomyces cerevisiae mitochondria: functional interactions among mitochondrial ribosomal protein Rsm28p, initiation factor 2, methionyl-tRNA-formyltransferase and novel protein Rmd9p.
Rsm28p is a dispensable component of the mitochondrial ribosomal small subunit in Saccharomyces cerevisiae that is not related to known proteins found in bacteria. It was identified as a dominant suppressor of certain mitochondrial mutations that reduced translation of the COX2 mRNA. To explore further the function of Rsm28p, we isolated mutations in other genes that caused a synthetic respiratory defective phenotype together with rsm28Delta. These mutations identified three nuclear genes: IFM1, which encodes the mitochondrial translation initiation factor 2 (IF2); FMT1, which encodes the methionyl-tRNA-formyltransferase; and RMD9, a gene of unknown function. The observed genetic interactions strongly suggest that the ribosomal protein Rsm28p and Ifm1p (IF2) have similar and partially overlapping functions in yeast mitochondrial translation initiation. Rmd9p, bearing a TAP-tag, was localized to mitochondria and exhibited roughly equal distribution in soluble and membrane-bound fractions. A small fraction of the Rmd9-TAP sedimented together with presumed monosomes, but not with either individual ribosomal subunit. Thus, Rmd9 is not a ribosomal protein, but may be a novel factor associated with initiating monosomes. The poorly respiring rsm28Delta, rmd9-V363I double mutant did not have a strong translation-defective phenotype, suggesting that Rmd9p may function upstream of translation initiation, perhaps at the level of localization of mitochondrially coded mRNAs.


Quality of infant feeding counselling for HIV+ mothers in Brazil: challenges and achievements.
This project aimed to assess the information and counselling on infant feeding in HIV+ mothers. A cross-sectional study, based on 118 structured observations of mothers' visits to health professionals (5-8/professional)-in 15 purposively selected HIV/Aids healthcare units in Sao Paulo. The general quality of communication and counselling skills was good: for example, professionals responded to all mothers' questions (98%); kept eye-to-eye contact (82%); encouraged the mother to talk (77.1%). However, the information provided to mothers aimed to help their choices concerning infant feeding was of very poor quality. No mother, for example, was informed about alternatives to formula feeding and the danger of mixed feeding. None was offered the option of using banked breast milk. Only around 20% of mothers were informed about the safe preparation of formula feeding. When counselled by a nutritionist (compared with a paediatrician) more mothers were informed about the correct way to prepare bottle-feeds. No mention was made of cup feeding. Although health workers have good communication skills, the information provided to HIV+ mothers is insufficient. Recommending against breast-feeding and providing infant formula may not be enough to achieve safer infant-feeding practices.


Monitoring and scoring counter-diffusion protein crystallization experiments in capillaries by in situ dynamic light scattering.
In this paper, we demonstrate the feasibility of using in situ Dynamic Light Scattering (DLS) to monitor counter-diffusion crystallization experiments in capillaries. Firstly, we have validated the quality of the DLS signal in thin capillaries, which is comparable to that obtained in standard quartz cuvettes. Then, we have carried out DLS measurements of a counter-diffusion crystallization experiment of glucose isomerase in capillaries of different diameters (0.1, 0.2 and 0.3 mm) in order to follow the temporal evolution of protein supersaturation. Finally, we have compared DLS data with optical recordings of the progression of the crystallization front and with a simulation model of counter-diffusion in 1D.


The establishing of Chinese medical concepts in Norwegian acupuncture schools: the cultural translation of jingluo ('circulation tracts').
Acupuncture and other forms of so-called alternative treatments, originating outside the West, have increasingly become an integrated part of the repertoire of medical practices widely used in health care remote from their places of origin. The main aim of this paper is to elucidate the cultural translation of Chinese medical concepts in a Western, acupuncture setting located far from China. Drawing on material from ethnographic fieldwork in acupuncture schools in Norway, this study discusses how concepts used in Chinese acupuncture are taught and interpreted for biomedically oriented students. The paper concentrates on the concept of jingluo ('circulation tracts', 'meridians') which the schools considered to be vital in order to conduct acupuncture. Similar to several other Chinese medical concepts, jingluo presents claims about the body that significantly differ from biomedical assumptions. The paper adds novel resources and insights to the research concerning medical conceptions, in that it applies the perspective of 'finitism' as developed in the field of sociology of knowledge by Barnes, Bloor and Henry (1996) in its analysis. It presents an analysis of five empirical examples demonstrating how a variety of interpretations of jingluo--many of them from different fields and some of them contradictory--were involved in establishing jingluo. Finally, by examining examples of Chinese concepts of the body, the paper seeks to contribute to the wider field of the anthropology of the body as well as to add to our understanding of the ways in which medical pluralism and globalisation of acupuncture unfolds.


DNA nanoparticles are safe and nontoxic in non-human primate eyes.
DNA nanoparticles (NPs) comprising polylysine conjugated to polyethylene glycol efficiently target murine photoreceptors and the retinal pigment epithelium (RPE) and lead to long-term phenotypic improvement in models of retinal degeneration. Advancing this technology requires testing in a large animal model, particularly with regard to safety. So, herein we evaluate NPs in non-human primates (baboon). NPs with plasmids carrying GFP and a ubiquitous, RPE-specific, or photoreceptor-specific promoter were delivered by either subretinal or intravitreal injection. We detected GFP message and protein in the retina/RPE from eyes dosed with NPs carrying ubiquitously expressed and RPE-specific vectors, and GFP message in eyes injected with NPs carrying photoreceptor-specific vectors. Importantly, we observed NP DNA in the retina/RPE following intravitreal injection, indicating the inner limiting membrane does not prevent NP diffusion into the outer retina. We did not observe any adverse events in any baboon, and there were no NP-associated changes in retinal function. Furthermore, no systemic or local inflammatory reaction to the vectors/injections was observed, and no NP DNA was found outside the eye. Taken together with the well-established rodent safety and efficacy data, these findings suggest that DNA NPs may be a safe and potentially clinically viable nonviral ocular therapy platform for retinal diseases.


Temporal dispersion of a spectrometer.
The temporal dispersion of an optical spectrometer has been characterized for a variety of conditions related to optical diagnostics to be fielded at the National Ignition Facility (e.g., full-aperture backscatter station, Thomson scattering). Significant time smear is introduced into these systems by the path length difference through the spectrometer. The temporal resolution is shown to depend only on the order of the grating, wavelength, and the number of grooves illuminated. To enhance the temporal resolution, the spectral gratings can be masked limiting the number of grooves illuminated. Experiments have been conducted to verify these calculations. The size and shape of masks are investigated and correlated with the exact shape of the temporal instrument function, which is required when interpreting temporally resolved data. The experiments used a 300 fs laser pulse and a picosecond optical streak camera to determine the temporal dispersion. This was done for multiple spectral orders, gratings, and optical masks.


The adhesion capability of Staphylococcus aureus cells is heterogeneously distributed over the cell envelope.
Understanding and controlling microbial adhesion is a critical challenge in biomedical research, given the profound impact of bacterial infections on global health. Many facets of bacterial adhesion, including the distribution of adhesion forces across the cell wall, remain poorly understood. While a recent 'patchy colloid' model has shed light on adhesion in Gram-negative Escherichia coli cells, a corresponding model for Gram-positive cells has been elusive. In this study, we employ single cell force spectroscopy to investigate the adhesion force of Staphylococcus aureus. Normally, only one contact point of the entire bacterial surface is measured. However, by using a sine-shaped surface and recording force-distance curves along a path perpendicular to the rippled structures, we can characterize almost a hemisphere of one and the same bacterium. This unique approach allows us to study a greater number of contact points between the bacterium and the surface compared to conventional flat substrata. Distributed over the bacterial surface, we identify sites of higher and lower adhesion, which we call 'patchy adhesion', reminiscent of the patchy colloid model. The experimental results show that only some cells exhibit particularly strong adhesion at certain locations. To gain a better understanding of these locations, a geometric model of the bacterial cell surface was created. The experimental results were best reproduced by a model that features a few (5-6) particularly strong adhesion sites (diameter about 250 nm) that are widely distributed over the cell surface. Within the simulated patches, the number of molecules or their individual adhesive strength is increased. A more detailed comparison shows that simple geometric considerations for interacting molecules are not sufficient, but rather strong angle-dependent molecule-substratum interactions are required. We discuss the implications of our results for the development of new materials and the design and analysis of future studies.


Reduction in deformed wing virus infection in larval and adult honey bees (Apis mellifera L.) by double-stranded RNA ingestion.
Deformed wing virus (DWV) is a serious pathogen of the honey bee, Apis mellifera L., vectored by the parasitic mite Varroa destructor. The virus is associated with wing deformity in symptomatic bees, and premature death and reduced colony performance in asymptomatic bees. In the present study we reduced DWV infection by feeding both first instar larvae and adult A. mellifera with a double-stranded (ds) RNA construct, DWV-dsRNA, which is specific to DWV in DWV-inoculated bees, by mixing it with their food. We showed that feeding DWV to larvae causes wing deformity in adult bees in the absence of varroa mites and decreases survival rates of adult bees relative to bees not fed DWV. Feeding larvae with DWV-dsRNA in advance of inoculation with virus reduced the DWV viral level and reduced wing deformity relative to larvae fed DWV or DWV with green fluorescent protein-dsRNA (probably a result of RNA silencing), but did not affect survival to the adult stage. Feeding DWV-dsRNA did not affect larval survival rates, which suggests that dsRNA is non-toxic to larvae. Feeding adult workers with DWV-dsRNA in advance of inoculation with virus increased their longevity and reduced DWV concentration relative to controls.


Roles of arabidopsis WRKY18, WRKY40 and WRKY60 transcription factors in plant responses to abscisic acid and abiotic stress.
WRKY transcription factors are involved in plant responses to both biotic and abiotic stresses. Arabidopsis WRKY18, WRKY40, and WRKY60 transcription factors interact both physically and functionally in plant defense responses. However, their role in plant abiotic stress response has not been directly analyzed. We report that the three WRKYs are involved in plant responses to abscisic acid (ABA) and abiotic stress. Through analysis of single, double, and triple mutants and overexpression lines for the WRKY genes, we have shown that WRKY18 and WRKY60 have a positive effect on plant ABA sensitivity for inhibition of seed germination and root growth. The same two WRKY genes also enhance plant sensitivity to salt and osmotic stress. WRKY40, on the other hand, antagonizes WRKY18 and WRKY60 in the effect on plant sensitivity to ABA and abiotic stress in germination and growth assays. Both WRKY18 and WRKY40 are rapidly induced by ABA, while induction of WRKY60 by ABA is delayed. ABA-inducible expression of WRKY60 is almost completely abolished in the wrky18 and wrky40 mutants. WRKY18 and WRKY40 recognize a cluster of W-box sequences in the WRKY60 promoter and activate WRKY60 expression in protoplasts. Thus, WRKY60 might be a direct target gene of WRKY18 and WRKY40 in ABA signaling. Using a stable transgenic reporter/effector system, we have shown that both WRKY18 and WRKY60 act as weak transcriptional activators while WRKY40 is a transcriptional repressor in plant cells. We propose that the three related WRKY transcription factors form a highly interacting regulatory network that modulates gene expression in both plant defense and stress responses by acting as either transcription activator or repressor.


Current distribution of Achatina fulica, in the state of São Paulo including records of Aelurostrongylus abstrusus (Nematoda) larvae infestation.
The currently known distribution range of Achatina fulica Bowdich, 1822, in the state of São Paulo, Brazil, is presented. The record of A. fulica naturally infested with Aelurostrongylus abstrusus larvae (Railliet, 1898) (Nematoda: Metastrongylidae) can be found in the city of Guaratinguetá. It was found A. fulica with Metastrongylidae larvae without known medical and veterinary importance in the cities of Carapicuíba, Embu-Guaçu, Itapevi, São Caetano do Sul, São Paulo and Taboão da Serra.


Histologic evaluation during healing of hydrogel core-and-skirt keratoprostheses in the rabbit eye.
We developed two models that are modifications of our original poly(2-hydroxyethyl methacrylate) (PHEMA) core-and-skirt keratoprosthesis. In these keratoprostheses, the mechanical strength of the skirt has been considerably increased with divinyl glycol (DVG) as a cross-linking agent during polymerization. In one (KPro I), methyl methacrylate (MMA) was added as comonomer to increase cell adhesion, and in the other (KPro II), HEMA was polymerized with DVG without comonomer. The aim of this study was to evaluate the process of healing and biocolonization and to ascertain whether KPro I demonstrates better ingrowth than the mechanically stronger KPro II, after implantation in rabbit eyes. Ten rabbits were used for each model and studied at five predetermined end points up to 26 weeks. The device was implanted as a full-thickness keratoprosthesis covered with a conjunctival flap. Neither prosthesis demonstrated extrusion or retroprosthetic membrane formation. There was no significant difference between the two types of prosthesis with respect to tissue ingrowth and surrounding tissue melting. Histologically, inflammation was not severe, but calcification was seen in most specimens. Evidence of biodegradation of the prosthesis also was seen. In our original keratoprosthesis, fibrovascular invasion had occurred into the prosthetic skirt, but wound dehiscence and low mechanical strength resulted in an unfavorable outcome. In this series, the mechanical properties were improved, and KPro II was stronger than KPro I. Therefore KPro II would be the preferred polymer combination for surgical manipulation. However, biodegradation and calcification require further investigation into the degree and significance of these adverse reactions.


Using a dynamic artificial digestive system to investigate heme iron nitrosylation during gastro-intestinal transit.
The International Agency for Research on Cancer recently classified cured meats as carcinogenic for humans and red meats as probably carcinogenic. Mutagens can be formed during meat process or digestion. In a previous study, we used a dynamic artificial digestive system (DIDGI®) to investigate protein oxidation and N-nitrosation during bovine meat digestion. This new paper completes the previous one by focusing on the endogenous heme iron nitrosylation. Low nitrosylation due to nitrate initially present in meat and to ammonia oxidation in the stomach was observed in the digestive tract even in conditions in which no nitrite was added to the model. The endogenous addition of nitrite (1 mM) considerably increased heme iron nitrosylation while a significant decrease was observed with prior meat cooking (30 min at 60 and 90 °C).


Differences in Overweight and Obesity Prevalence in Middle-Aged Men from Twelve Middle Eastern and Asian Countries Living in Saudi Arabia.
This study was conducted to determine differences in overweight and obesity prevalence and the associated sociodemographic variables among middle-aged men from twelve Middle Eastern and Asian countries living in Riyadh, Saudi Arabia. This is a cross-sectional study. The study sample was chosen randomly using a stratified clustered sampling technique. The weight and height of 1800 middle-aged men (36 to 59 years) from twelve Middle Eastern and Asian countries living in Riyadh, Saudi Arabia, were measured using standardized methods. Face-to-face interviews were used to gather sociodemographic information from participants. Overweight and obesity were reported among 51.9% and 14.7% of participants, respectively. Nationality was a predictor of overweight and obesity. Subjects from Bangladesh and Saudi Arabia had the lowest (41.0%) and highest (85.1%) rates of overweight and obesity, respectively. Increasing age, staying in Saudi Arabia for a longer period, being single, and earning a high monthly income were associated with a significantly higher risk of overweight and obesity among the participants. The findings revealed significant differences in the prevalence of overweight and obesity among participants from different countries living in Saudi Arabia. Sociodemographic variables associated with overweight and obesity among participants were identified.


Computational insights into the acceptor chemistry of phosphenium cations.
Phosphines are traditionally considered as Lewis bases or ligands in transition metal and main group complexes. Despite their electron-rich (lone pair-bearing) nature, an extensive coordination chemistry for Lewis acidic phosphorus centers is being developed; such chemistry provides a new synthetic approach for phosphorus-element bond formation, leading to new types of structures and modes of bonding. Complexes of Ph2P+ with a variety of donor elements (P, N, C) give experimentally short donor-acceptor bond lengths, when compared to other cationic phosphorus Lewis acid complexes. We have calculated that the energy of the lowest unoccupied molecular orbital (LUMO) in Ph2P+ is lower than that of (Me2N)2P+, which partially explains the greater exothermicity of reactions of donors with the diaryl acceptor. Furthermore, the energies required to distort the diphenylphosphenium cation from its ground-state geometry are significantly smaller than those of the diamido cations and, thus, enhance the exothermicity of donor coordination. These computational data, in conjunction with evidence from experimental solid-state structures, indicate that Ph2P+ is a significantly better Lewis acid relative to the more common diaminophosphenium analogues (R2N)2P+ and are used to elucidate the nature of the bonding in donor-phosphenium complexes.


Sexual function and dysfunction in younger married alcoholics. A comparative study.
Sexual dysfunction in male and female alcoholic addicts was evaluated in a comparative study of 60 married alcoholics and an age-matched control group from a general practitioner's clinic. 63% of the alcoholic men reported sexual dysfunction - mainly erectile and libido disorders - compared with 10% in the control group. The frequency of sexual dysfunction in alcoholic women did not differ from that in controls. Approximately 25% of the women who reported sexual dysfunction had reduced libido. The male alcoholics claim the aversive treatment, (Antabus), to be the causative factor, and considered their problem began as soon as they started treatment. There was no change in masturbation or coital frequency in the month before and after initiation of treatment. The study discusses present knowledge of relevant etiological factors in sexual function and dysfunction in alcoholics - implicating a multifacetted therapeutic approach.


Recent trends in colonic diverticulosis in Yokohama City: a possibility of changing to a more Western profile.
Right-sided type colonic diverticulosis has been predominant in Japan, in contrast to European counties where the left-sided type is predominant. Considering the recent change in the dietary habits of Japanese people to a more Western diet in urban areas of Japan, the features of colonic diverticulosis may also change to reflect a more Western type. Therefore, we attempted to clarify the current situation. A total of 435 consecutive outpatients who agreed to a barium enema and complete examination were enrolled in this study. 113 patients (26.0%) revealed colon diverticulosis; 50.4% of the patients had more than ten diverticula. The percentage of man with ten or more diverticula (67.4%) was significantly higher than that of women patients (40.0%, p<0.01). Among the 88 patients who had four or more diverticula, 39 patients (44.3%) were right-side dominant, 27 (30.7%) left-side dominant and 22 (25.0%) were both-sides. Thirteen (68.4%) of the 19 patients who had more than 30 diverticula were left-side dominant. The clinical features of colon diverticulosis in the patients living in Yokohama may be changing to reflect a more Western type, in particular decreased right-side dominance, increases in the left-side and both-sides dominant patients, and the emergence of patients with crowded diverticula in the left-side colon was observed.


Transcutaneous measurement of renal function in conscious mice.
Determination of glomerular filtration rate (GFR) in conscious mice is cumbersome for the experimenter and stressful for the animals. Here we report on a simple new technique allowing the transcutaneous measurement of GFR in conscious mice. This approach extends our previously developed technique for rats to mice. The technique relies on a miniaturized device equipped with an internal memory that permits the transcutaneous measurement of the elimination kinetics of the fluorescent renal marker FITC-sinistrin. This device is described and validated compared with FITC-sinistrin plasma clearance in healthy, unilaterally nephrectomized and pcy mice. In summary, we describe a technique allowing the measurement of renal function in freely moving mice independent of blood or urine sampling as well as of laboratory assays.


Particulate contamination in New Zealand intravenous solutions.
The New Zealand Department of Health sampled intravenous solutions readily available, February to April 1978, for testing at DSIR. Four out of a sample of 12 production batches taken from five manufacturers failed to comply with the requirements for particulate matter of the British Pharmacopoeia 1973 and of the New Zealand Transfusion Advisory Committee. A further 15 batches were rejected when retesting products of two manufacturing units where problems with particulate contamination had been descovered. Subsequently, action has been taken to deal with these problems.


Targeting protein kinase A in cancer therapy: an update.
Protein Kinase A (PKA) is a well known member of the serine-threonin protein kinase superfamily. PKA, also known as cAMP-dependent protein kinase, is a multi-unit protein kinase that mediates signal transduction of G-protein coupled receptors through its activation upon cAMP binding. The widespread expression of PKA subunit genes, and the myriad of mechanisms by which cAMP is regulated within a cell suggest that PKA signaling is one of extreme importance to cellular function. It is involved in the control of a wide variety of cellular processes from metabolism to ion channel activation, cell growth and differentiation, gene expression and apoptosis. Importantly, since it has been implicated in the initiation and progression of many tumors, PKA has been proposed as a novel biomarker for cancer detection, and as a potential molecular target for cancer therapy. Here, we highlight some features of cAMP/PKA signaling that are relevant to cancer biology and present an update on targeting PKA in cancer therapy.


IL-1beta induces alkaline phosphatase in human phagocytes.
Alkaline phosphatase (ALPase) is found in blood plasma or serum and leukocytes and regulates intercellular processes, maintaining phosphoryl metabolites in a steady state, as well as synthesizing and hydrolyzing phosphate esters on membranes. ALPase supervises the active transport of inorganic phosphates, fats, proteins, carbohydrates and the sodium/potassium pump mechanisms. The formed elements of blood such as polymorphonuclear (PMNs) leucocytes, macrophages (MP) and some lymphocytes are high in ALPase concentrations. In this study we have tested whether the interleukin-1 receptor antagonist (IL-lra) could influence ALPase generation in IL-1beta or lipopolysaccharide (LPS)-stimulated neutrophils and MP. Human neutrophils were isolated from heparin-anticoagulated blood drawn from healthy individuals by centrifugation in a two-step gradient, Ficoll-Hypaque. ALPase activity was assessed spectrophotometrically in test tubes containing isolated neutrophils and adherence PBMCs treated with LPS, IL-1beta and IL-1ra, alone or in combination. IL-lbeta or LPS enhanced ALPase in both PMNs and MP, whereas IL-1ra could not inhibit ALPase activity. We performed time course experiments at 0 min, 5 min, 1 h, 24 h, and 43 h (LPS 20 microg/mL, IL-1beta 10 ng/mL). No significant increase in ALPase activity was seen until 1 h; however, there was a rapid rise over the next few hours. In another set of experiments using IL-1ra (500 ng/mL), there was no difference between treated cells and control cells. The combination of IL-1beta plus IL-1ra did not reduce the ability of IL-1beta to induce ALPase activity. These data suggest that IL-1beta stimulates ALPase through other mechanisms than the release of arachidonic acid products, which are inhibited by IL-lra.


Effect of a combination of butorphanol and detomidine on endoscopic assessment of laryngeal function in Thoroughbred yearlings.
To the authors' knowledge, the effect of a combination of butorphanol tartrate and detomidine hydrochloride on the laryngeal function and symmetry of the arytenoid cartilages in young Thoroughbred horses has not been examined. Therefore, this study aimed to examine the effects of administration of butorphanol and detomidine on left-to-right rima glottidis ratio (L:R RGR), cross-sectional area of the rima glottidis (CSARG) and grade of laryngeal function of Thoroughbred yearlings examined endoscopically at rest. Forty-six Thoroughbred yearlings underwent laryngeal video endoscopy, at rest, before and after sedation with butorphanol and detomidine. Three clinicians assigned grades of laryngeal function after reviewing the video recordings. The L:R RGR and CSARG were measured at the point of arytenoid cartilages' maximal abduction. Student's t-test was used to compare the L:R RGR and CSARG. Cohen's kappa (κ) was used to compare the intra- and interobserver agreements. Spearman's rank order was used to assess agreement between CSARG and grade of laryngeal function. Sedation had no effect on L:R RGR and CSARG. Mean intraobserver agreement of grade of laryngeal function of unsedated yearlings was 93.1%, and that of sedated yearlings was 92.9%. Mean interobserver agreement of grade of laryngeal function of unsedated yearlings was 92.8%, and that of sedated yearlings was 92.7%. Correlation between CSARG and laryngeal function grade was significant for both groups (p < 0.001). Sedating Thoroughbred yearlings with detomidine and butorphanol, before endoscopically examining the larynx, did not significantly affect the grade of laryngeal function.


Clinical outcome of diabetic foot ulcers treated with negative pressure wound therapy and the transition from acute care to home care.
Diabetic foot ulcers affect millions of people in the United States of America and impose tremendous medical, psychosocial and financial loss or burden. Negative pressure wound therapy (NPWT) is generally well tolerated and appears to stimulate a robust granulation tissue response compared with other wound healing modalities. This device may be a cost-effective adjunctive wound healing therapy. This literature review will focus on the clinical outcome of diabetic foot ulcers treated with NPWT, its implication in the transition from acute care to home care, factors that might influence clinical outcomes in home care as well as quality-of-life aspects in these patients. Patient care for diabetic foot ulceration is complex and necessitates multiprofessional collaboration to provide comprehensive wound care. It is clear that when we strive for limb preservation in this most high-risk population, it is important to have an available versatile, efficacious wound healing modality. There is a need for an easy transition from acute care to home care. Resources need to be combined in a collaborative and synergistic fashion to allow patient to perform many daily living activities while receiving the potential benefits of an advanced wound healing modality.


Clinical use of lenvatinib in combination with everolimus for the treatment of advanced renal cell carcinoma.
Renal cell carcinoma (RCC) represents 2%-3% of all cancers in adults, and its pathogenesis is mainly related to altered cellular response to hypoxia. Lenvatinib, a novel multitarget tyrosine kinase inhibitor (TKI), represents a therapeutic option, in combination with mammalian target of rapamycin (mTOR) inhibitor everolimus, for the treatment of metastatic RCC (mRCC). The objective of this article is to review the evidence about the treatment of mRCC with combination of lenvatinib plus everolimus. Phase I studies supported clinical activity of lenvatinib in mRCC. A randomized, Phase II, open-label, multicenter trial demonstrated the clinical efficacy of combination treatment with lenvatinib plus everolimus in patients with progressive mRCC after prior therapy with TKI. Median progression-free survival was improved by 9 months with the combination therapy compared to the single-agent everolimus, with an overall response rate of 43% for the experimental regimen. Lenvatinib plus everolimus appeared to be slightly less toxic than single-agent lenvatinib and more toxic than single-agent everolimus; grade 3-4 adverse events occurred in 71% of patients. Currently, lenvatinib plus everolimus has US Food and Drug Administration approval for its use in mRCC after failure of previous treatment with TKI. The combination therapy with lenvatinib plus everolimus might be a promising choice for second-line treatment of mRCC patients. Based on the results of the Phase II trial, it is possible to speculate that the combination therapy could be appropriate for patients with high disease burden or strongly symptomatic patients.


TCR usage and functional capabilities of human gamma delta T cells at birth.
Little is known about the gamma delta T cells in human neonatal umbilical cord blood. To compare neonatal cord blood and adult blood gamma delta T cells, we studied the V gamma and V delta gene segment usage in these populations by flow cytometry, and we derived cord blood gamma delta T cell clones to determine their functional capabilities. Unlike adult blood gamma delta T cells that predominantly express V gamma 2V delta 2 TCRs, neonatal cord blood gamma delta T cells expressed diverse V gamma and V delta gene segments paired in a variety of combinations rarely observed in adults. gamma delta T cell clones derived from neonatal cord blood similarly expressed a diverse array of TCRs. These cord blood-derived gamma delta T cell clones had weak cytolytic activity when assayed for K562 tumor cell killing, lectin-mediated cytolysis, and redirected cytolysis. They also expressed lower levels of the CD2, LFA-1, and CD45RO cell surface receptors as compared with strongly cytolytic adult gamma delta T cell clones. These properties of the cord blood-derived gamma delta T cell clones, weak cytotoxic activity and low adhesion molecule expression, were similar to the properties of the CD4+ subset of adult gamma delta T cells. Thus, neonatal gamma delta T cells are functionally different from the majority of adult gamma delta T cells and display a distinct TCR repertoire and accessory molecule profile.


Cardiac volumetry. Comparison of echoplanar and conventional cine-magnetic resonance data-acquisition strategies.
Ejection fraction (EF) measurements obtained using conventional cine-magnetic resonance imaging (MRI) are accurate but time-consuming. With echoplanar imaging (EPI), these data can be acquired much faster. In this study, EF and cardiac output (CO) measurements based on EPI data are compared with those measurements based on cine-MRI images. Twelve subjects were examined on a 1.5-T imager equipped with a special EPI gradient system. The entire heart was imaged with contiguous axial 10-mm sections using cine-MRI and EPI techniques. With cine-MRI, 20 frames were acquired over 256 cardiac cycles; with EPI, 24 frames were obtained over four RR intervals using an electrocardiogram-triggered four-shot acquisition strategy. Ejection fraction and CO were calculated based on the summation of the individual end-systolic and end-diastolic volumes. Ejection fraction and CO measurements based on the two different data sets were compared. Multishot EPI was 50 times faster than cine-MRI. The short acquisition time permitted breath-hold imaging. The high temporal (16 to 24 frames/RR interval) and spatial resolution (1.56 x 1.56 mm in plane) of the multishot EPI images enabled delineation of the ventricular lumen at end-systole and end-diastole in a fashion similar to cine-MRI. Echoplanar imaging EF and CO measurements correlated well with cine-MRI EF measurements, with correlation coefficients of 0.96 and 0.94, respectively. The 95% confidence interval of the EF measurement differences between the two techniques was narrow, ranging from -5.2 to 5.7 EF percentage points. Accurate volumetric EF and CO measurements are possible based on ultrafast multishot EPI data sets as part of an integrated MRI-based cardiac evaluation.


Determinants of vaccination coverage and adherence to the Greek national immunization program among infants aged 2-24 months at the beginning of the economic crisis (2009-2011).
Childhood immunization has significantly reduced the incidence of vaccine preventable diseases. Parental mistrust over vaccine safety has been associated with vaccine refusal creating barriers on vaccine coverage. Recently, economic crisis has imposed additional impediment. Study aim was to evaluate vaccine coverage among infants 2-24 months old in the Athens metropolitan area at the beginning of the economic crisis (2009-2011). Overall, 1,667 infants were enrolled (mean age 13 months). Less than 5% of parents admitted omitting or postponing vaccination secondary to their beliefs. Although vaccination coverage was acceptable for most vaccines, lower rates of immunization were found for some newer vaccines such as hepatitis A and rotavirus. Multiple regression analysis indicated that parental age, occupational, educational statuses and family size were independently associated with immunization coverage at 6 and 12 months. Interestingly, lack of insurance was not associated with missed vaccine doses. Incomplete vaccination coverage was associated with socioeconomic factors. It becomes apparent, that reassessing vaccination priorities under the current economic situation may be needed.


Protein arginine-methyltransferase-dependent oncogenesis.
Enzymes that mediate reversible epigenetic modifications have not only been recognized as key in regulating gene expression and oncogenesis, but also provide potential targets for molecular therapy. Although the methylation of arginine 3 of histone 4 (H4R3) by protein arginine methyltransferase 1 (PRMT1) is a critical modification for active chromatin and prevention of heterochromatin spread, there has been no direct evidence of any role of PRMTs in cancer. Here, we show that PRMT1 is an essential component of a novel Mixed Lineage Leukaemia (MLL) oncogenic transcriptional complex with both histone acetylation and H4R3 methylation activities, which also correlate with the expression of critical MLL downstream targets. Direct fusion of MLL with PRMT1 or Sam68, a bridging molecule in the complex for PRMT1 interaction, could enhance self-renewal of primary haematopoietic cells. Conversely, specific knockdown of PRMT1 or Sam68 expression suppressed MLL-mediated transformation. This study not only functionally dissects the oncogenic transcriptional machinery associated with an MLL fusion complex, but also uncovers--for the first time--an essential function of PRMTs in oncogenesis and reveals their potential as novel therapeutic targets in human cancer.


Perceived Sexual Difficulties and Sexual Counseling in Men and Women Across Heart Diagnoses: A Nationwide Cross-Sectional Study.
Ischemic heart disease and heart failure often lead to sexual difficulties in men, but little is known about the sexual difficulties in women and patients with other heart diagnoses or the level of information patients receive about the risk of sexual difficulties. To investigate perceived sexual difficulties and associated factors in a mixed population of men and women newly diagnosed with heart disease and provide insight into sexual counseling and information given by health care professionals. This article reports on a cross-sectional, questionnaire study sent to a randomly selected sample of men and women newly diagnosed with heart failure, ischemic heart disease, atrial fibrillation, or heart valve surgery. Eligible patients were identified by diagnosis using the Danish National Patient Register, which contains all diagnoses. Sexual difficulties were self-reported using single-item questions, and factors associated with sexual difficulties were collected from the survey and national registers. The study population consisted of 1,549 men and 807 women (35-98 years old) with heart failure (n = 243), ischemic heart disease (n = 1,036), heart valve surgery (n = 375), and atrial fibrillation (n = 702). Sexual difficulties were reported by 55% of men and 29% of women. In a multiple regression analysis, difficulties in men were associated with being older (≥75 years old; odds ratio [OR] = 1.97, 95% CI = 1.13-3.43), having heart failure (OR = 2.07, 95% CI = 1.16-3.71), diabetes (OR = 1.80, 95% CI = 1.15-2.82), hypertension (OR = 1.43, 95% CI = 1.06-1.93), receiving β-blockers (OR = 1.37, 95% CI = 1.02-1.86), or having anxiety (OR = 2.25, 95% CI = 1.34-3.80) or depression (OR = 2.74, 95% CI = 1.38-5.43). In women, difficulties were significantly associated with anxiety (OR = 3.00, 95% CI = 1.51-5.95). A total of 48.6% of men and 58.8% of women did not feel informed about sexuality, and 18.1% of men and 10.3% of women were offered sexual counseling. Heart disease increases the risk of sexual difficulties and there is a need for improved information and counseling about sex and relationships for patients. This large nationwide survey of men and women combined a survey with administrative data from national registries. However, this study used non-validated single-item questions to assess sexual difficulties without addressing sexual distress. More than half the men and one fourth the women across common heart diagnoses had sexual difficulties. No difference was found among diagnoses, except heart failure in men. Despite guidelines recommending sexual counseling, sexual difficulties were not met by sufficient information and counseling. Rundblad L, Zwisler AD, Johansen PP, et al. Perceived Sexual Difficulties and Sexual Counseling in Men and Women Across Heart Diagnoses: A Nationwide Cross-Sectional Study. J Sex Med 2017;14:785-796.


Transient severe metastatic calcification in acute renal failure.
Metastatic calcification, a known complication of prolonged end-stage renal disease, is herein described for the first time in a 10-month-old boy with acute renal failure, manifesting as a painful and swollen arm. Imaging revealed diffuse calcification and technetium-99 methylene diphosphonate (99Tc-MDP) uptake around the humerus and axilla. Calcium and vitamin D restriction, followed by intravenous administration of sodium thiosulfate caused a full symptomatic, radio- and scintigraphic improvement.


A Tale of Two Audiences: Formative Research and Campaign Development for Two Different Latino Audiences, to Improve COVID-19 Prevention Behavior.
The COVID-19 pandemic disproportionately affected the Latino population in the United States, further exacerbating the existing racial and ethnic health disparities that this group faces. While government health entities rushed to develop COVID-19 prevention educational materials in Spanish, these failed to recognize the unique motivators and barriers that move different Latino audience segments to act. We conducted five online focus groups with two different Latino audience segments, general Latino people, and Latino migrant workers, to assess their experience navigating the pandemic, their engagement in preventive behavior, and their consumption of health news. While the general Latino audience had higher levels of social capital and established preventive healthcare, they were more skeptical about getting the COVID-19 vaccine. Migrant workers needed to be vaccinated to retain their jobs, and saw the vaccine as the only way to keep their families healthy. We used the focus group results to develop two different creative concepts that aligned with each audience's unique experience. Our study highlights the importance of developing hyper-focused messages, responsive to the experience of distinct audience segments, for maximum impact.


Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS-CoV-2.
17 years after the SARS-CoV epidemic, the world is facing the COVID-19 pandemic. COVID-19 is caused by a coronavirus named SARS-CoV-2. Given the most optimistic projections estimating that it will take over a year to develop a vaccine, the best short-term strategy may lie in identifying virus-specific targets for small molecule interventions. All coronaviruses utilize a molecular mechanism called -1 PRF to control the relative expression of their proteins. Prior analyses of SARS-CoV revealed that it employs a structurally unique three-stemmed mRNA pseudoknot to stimulate high rates of -1 PRF, and that it also harbors a -1 PRF attenuation element. Altering -1 PRF activity negatively impacts virus replication, suggesting that this molecular mechanism may be therapeutically targeted. Here we present a comparative analysis of the original SARS-CoV and SARS-CoV-2 frameshift signals. Structural and functional analyses revealed that both elements promote similar rates of -1 PRF and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablated -1 PRF activity. The upstream attenuator hairpin activity has also been functionally retained. Small-angle x-ray scattering indicated that the pseudoknots in SARS-CoV and SARS-CoV-2 had the same conformation. Finally, a small molecule previously shown to bind the SARS-CoV pseudoknot and inhibit -1 PRF was similarly effective against -1 PRF in SARS-CoV-2, suggesting that such frameshift inhibitors may provide promising lead compounds to counter the current pandemic.


Coxiella burnetii Infection With Severe Hyperferritinemia in an Asplenic Patient.
Q fever is an uncommon but likely underreported zoonotic infection. Severe hyperferritinemia has been associated with hemophagocytic lymphohistiocytosis and other infectious diseases. In this study, we report a case of Coxiella burnetii infection in an asplenic patient complicated by severe hyperferritinemia and bone marrow infiltration. In this case, the marked ferritin elevation may have been an indicator of profound systemic macrophage activation due to preferential intracellular infection of this cell type by C burnetii, perhaps exacerbated by altered mononuclear phagocyte system function in the setting of asplenia.


Cell-associated transmission of HIV type 1 and other lentiviruses in small-animal models.
Small-animal models of lentivirus transmission have repeatedly demonstrated transmission by cell-associated virus via vaginal, rectal, and oral routes. The earliest experiments were in the cat/feline immunodeficiency virus model, followed a decade later by successful vaginal transmission of cell-associated human immunodeficiency virus (HIV) in mice bearing transplanted human immune cells. After early unsuccessful attempts at cell-associated transmission in nonhuman primates, renewed investigation in diverse primate models has now confirmed the findings from the cat and humanized mouse models. Improvements in humanized mouse models have made them the preferred small-animal models to study HIV mucosal transmission. They provide complementary systems to nonhuman primate models to aid in the elucidation of the many remaining questions on the mechanism of and means to prevent both cell-associated and cell-free HIV transmission across mucosal barriers.


Insight into the binding interaction of kaempferol-7-O-α-L-rhamnopyranoside with human serum albumin by multiple fluorescence spectroscopy and molecular modeling.
Human serum albumin (HSA) is a transporting protein that has multiple functions. The binding interaction between HSA and small molecules affects its function and efficacy of small molecules. The present study reports that kaempferol-7-O-α-L-rhamnopyranoside (KR) interacts with HSA as indicated by multiple fluorescence spectroscopy and molecular modeling. KR can quench the intrinsic fluorescence of HSA through the formation of a KR-HSA complex in a static manner. In addition, the binding site is located in subdomain IIA as confirmed by competitive experiments using site-specific warfarin and ibuprofen, and the driving forces include hydrogen bonds, van der Waals forces and electrostatic interaction derived from a thermodynamic analysis. The formation of KR-HSA is exothermic and spontaneous. Although there is no hydrophobic interaction around Tyr and Trp residues, the secondary structure of HSA changes through the formation of the KR-HSA complex. In addition, docking results visualized and further supported these results. Finally, these results can provide more information to further investigate the use of KR on the prevention of diabetic complications.


[Effect of different mechanical loading on the expression of Notch signaling pathways in growing rabbits' condylar cartilage].
Objective: To investigate the effect of different mechanical loading on the expression of Notch-1, Notch-3, Jagged-1 and Delta-like-1 in growing rabbits' condylar cartilage. Methods: Sixty-four ten-days-old rabbits were randomly divided into experimental and control groups. The rabbits in the experimental groups were fed on a powder diet, while the control groups were fed on a solid diet. The animals were sacrificed after 2, 4, 6 and 8 weeks. Notch-1, Notch-3, Jagged-1 and Delta-like-1 gene and protein expressions were examined by HE, immunohistochemistry, Western blotting and quantitative real-time PCR. Results: At 2, 4, 6, 8 weeks, the anterior part of condylar cartilage in solid diet groups ([318.1±4.3], [342.4±2.6], [364.2±3.2], [380.7±6.0] mm, respectively) were thicker than those in powder diet groups ([275.4±2.6], [301.1±2.0], [322.3±3.3], [366.5±8.4] mm, respectively) (P<0.05). There was no significant difference between the two groups in the middle part (P>0.05). From 2 to 6 weeks, the posterior part of cartilage in solid diet groups ([444.1±1.5], [451.1±0.3], [476.4±5.7] mm, respectively) was thinner than those in power diet groups ([470.4±2.7], [494.3±2.9], [512.3±5.7] mm, respectively) (P<0.05). At 6 weeks, there were more mRNA expressions of Notch-3, Jagged-1 and Delta-like-1 in solid diet group than in power diet group (P<0.05). The Notch-1 protein could be found in all layers of condylar cartilage, especially in the surface of hypertrophic zone. The expressions of Notch-1, Notch-3, and Delta-like-1 protein were increased from 2 to 6 weeks, and decreased at 8 weeks. In solid diet groups, the protein expressions of Notch-1 (at 2, 4, 6, 8 weeks), Notch-3 (at 2, 4, 6 weeks), Jagged-1 (at 2, 4, 6 weeks) and Delta-like-1 (at 4, 6, 8 weeks) were greater than in power diet groups (P<0.05). Conclusions: Low masticatory loading may delay or inhibit the development of condylar cartilage and its growing factors such as Notch-1, Notch-3, Jagged-1 and Delta-like-1. Appropriate masticatory loading plays an important role in normal development of the condyle.


Tetrahedral Framework Nucleic Acids Ameliorate Insulin Resistance in Type 2 Diabetes Mellitus via the PI3K/Akt Pathway.
Insulin resistance (IR) is one of the essential conditions in the development of type 2 diabetes mellitus (T2DM). IR occurs in hepatic cells when the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is downregulated; thus, activating this pathway can significantly improve insulin sensitivity and ameliorate T2DM. Tetrahedral framework nucleic acids (tFNAs), a DNA nanomaterial, are synthesized from four single-stranded DNA molecules. tFNAs possess excellent biocompatibility and good water solubility and stability. tFNAs can promote cell proliferation, cell autophagy, wound healing, and nerve regeneration by activating the PI3K/Akt pathway. Herein, we explore the effects and underlying mechanisms of tFNAs on IR. The results displayed that tFNAs could increase glucose uptake and ameliorate IR by activating the IRS-1/PI3K/Akt pathway in glucosamine (GlcN)-stimulated HepG2 cells. By employing a PI3K inhibitor, we confirmed that tFNAs reduce IR through the PI3K/Akt pathway. Moreover, tFNAs can promote hepatic cell proliferation and inhibit GlcN-induced cell apoptosis. In a T2DM mouse model, tFNAs reduce blood glucose levels and ameliorate hepatic IR via the PI3K/Akt pathway. Taken together, tFNAs can improve hepatic IR and alleviate T2DM through the PI3K/Akt pathway, making contribution to the potential application of tFNAs in T2DM.


Tannic acid and oxidized tannic acid on the functional state of rat intestinal epithelium.
Diets containing tannic acid at the level of 3% of dry matter were fed to rats in order to ascertain the origin of fecal nitrogen and the effect of tannic acid on the intestinal mucosa. At the same time in order to explain the effect of oxidation of tannins, we administered diets containing oxidized tannic acid or tannic acid associated with an antioxidizer (sodium sulfite) at the level of 1% of dry matter. The increased excretion of sialic acid and glucosamine during ingestion of tannic acid indicated that the excess of fecal nitrogen mainly corresponds to the mucus hypersecretion observed by histology. Fecal analysis revealed perturbations in movements of water and ions. The study of the metabolic activity of isolated enterocytes and the activity of some enzymes in a homogenate of these cells showed an inhibition of oxygen consumption and succinic dehydrogenase activity. Addition of reducing agent (sodium sulfite) to the diet had little effect on the action of tannic acid; but previous oxidation of the tannin reduced the effects observed, particularly in the case of fecal nitrogen loss.


Renal function improves with the treatment of hypothyroidism.
It has been known that thyroid hormones may affect renal function. In this study, we aimed to investigate the effect of levothyroxine replacement on renal function in hypothyroid patients before and after treatment. We retrospectively investigated free T3 (fT3), free T4 (fT4), TSH, creatinine, and eGFR measurements during both hypothyroid and euthyroid states of hypothyroid patients. The eGFR was calculated using the simplified Modification of Diet in Renal Disease formula. fT3, fT4, and eGFR measurements increased, meanwhile creatinine and TSH levels decreased significantly after euthyroidism was achieved with levothyroxine treatment (p < 0.0001 for all). The correlation analyses revealed that ∆creatinine and ∆TSH levels were significantly correlated before and after levothyroxine treatment (r: 0.288, p < 0.0001). ∆eGFR and ∆TSH levels were significantly correlated before and after LT4 treatment (r: -0.272, p < 0.0001). In this study, we evaluated creatinine and eGFR levels in patients with hypothyroidism and found out that renal function improved in most patients after euthyroidism was achieved. In some patients, above-normal creatinine levels completely returned to normal once the patients became euthyroid.


EFFECTS OF SALVIA MILTIORRHIZAE ON THE KIDNEY OF RATS WITH SEVERE ACUTE PANCREATITIS AND OBSTRUTIVE JAUNDICE.
Severe acute pancreatitis (SAP) and obstructive jaundice (OJ) are frequent recurring diseases that bring about huge threat to human health. Some reports have demonstrated that Salviae miltiorrhizae can protect multiple organs of SAP and OJ model animals or patients, but their related mechanisms were not clear. In this study, we observed the effects of Salvia miltiorrhizae injection on apoptosis and NF-κB expression in kidney and explored the protective effect and mechanism of Salvia miltiorrhizae on the kidney of SAP or OJ rats. The results obtained will provide a theoretical basis for clinical application of Salvia miltiorrhizae. A total of 288 rats were used for SAP -and OJ-associated experiments. The mortality rates of rats, the contents of serum BUN and CREA, the expression levels of Bax, NF-κB proteins and the apoptosis index were observed, respectively. The pathological changes in the kidney of SAP or OJ rats in treated group were mitigated to varying degrees. At 6 and 12 hours after operation in SAP rats or on 21 and 28 days after operation in OJ rats, the contents of serum CREA in treated group were significantly lower than those in model control group; At 3 and 6 hours after operation, the staining intensity of Bax protein of kidney in treated group was significantly lower than that in model control group; on 14 days after operation, the apoptosis index in the kidney of OJ rats in treated group was significantly lower than that in model control group. Salvia miltiorrhizae can exert protective effects on the kidney of SAP and OJ rats.


Morganella morganii: A Rare Cause of Early-Onset Neonatal Sepsis.
Morganella morganii is an opportunistic Gram-negative bacillus commonly found in the human gastrointestinal tract and the environment. In adults, it is often associated with nosocomial infections, primarily surgical wound infections, urinary tract infections, and hepatobiliary infections. It is a rare cause of early-onset neonatal sepsis, with fewer than 15 reported cases in the literature. The authors aim to present a case of a low birth weight preterm born at 28 weeks' gestation, who developed early-onset neonatal sepsis due to M. morganii. We successfully treated the infection using a combination of third-generation cephalosporin and aminoglycoside, and in this report, we explain the rationale behind employing this antibiotic therapy.


Enhanced sensitivity of mdx mice to intramuscular injection of compound 48/80.
Species-specific differences in the inflammatory response, specifically with regard to mast cells, have been proposed to explain the phenotypic variation among dystrophin-deficient humans, and mdx mice (Gorospe et al., 1994). To test this hypothesis we have intramuscularly injected a mast cell secretogogue into both dystrophin-negative mdx and dystrophin-positive normal mice. Mast cell activity was determined by measuring the activity of mast cell tryptase, while creatine kinase activity was used to determine the course of muscle damage in vivo. Area of damage around the injection site was measured at autopsy, and used as an indication of relative sensitivity to the secretogogue effect of compound 48/80. Mdx mice exhibited more damage in response to intramuscular injection than normal control mice. In addition, mdx mice showed a substantial increase in plasma tryptase activity, followed by a large increase in muscle creatine kinase activity. On the other hand, dystrophin-positive normal controls injected with 48/80 liberated little CK or tryptase activity. These results are consistent with the hypothesis that species-specific differences in mast cell activity, or sensitivity to mast cell products could account for the variation in pathology seen in dystrophin-deficient animals.


[Value of combined conventional and contrast enhanced sonography in the evaluation of hepatic disorders].
To assess the value of combined conventional and contrast-material enhanced sonography for the characterization of focal liver lesions. Simultaneous imaging with grey scale and contrast enhanced US was performed in 90 patients following Levovist injection (Schering, Berlin, Germany) using the "Agent Detection Imaging" method (ADI, Siemens-Acuson, Mountain View, USA). US scanning was performed at least 4 minutes after contrast injection with review of both grayscale and contrast enhanced modes. Results for detection and characterization of lesions were compared to the selected gold standard imaging modality (CT or MRI). Final diagnoses included: 20 normal examinations, 41 patients with metastases, 6 patients with hepatocellular carcinoma, 13 patients with hemangioma, 6 patients with other benign lesions, 4 patients with cysts and 6 patients with two types of lesions. Delayed phase contrast enhanced US allowed diagnosis of all lesions except for one metastasis and all hepatocellular carcinomas. While the diagnosis of hepatoma could not be confirmed, the features suggested a malignant etiology. For 7 patients with metastases, more lesions were detected at ADI (4.9 lesions) than at conventional US (1.1 lesion). For 3 patients, CT showed more lesions than ADI US (3.3 versus 1.6 lesions). The accuracy of ADI US for differentiating between benign and malignant lesions was 98.7% compared to 49.6% for conventional US (p<0.001). The total number of lesions detected at ADI US was higher (p<0.01) than at conventional US and not significantly different from that obtained by the gold standard reference methods. Complete characterization was achieved in 92.2% of cases with ADI US compared to 59.2% with conventional US (p<0.001). Contrast-material enhanced US combined with conventional US markedly improves the diagnostic accuracy of US in terms of lesion detection and characterization.


Subjective effects of antidepressants: a pilot study of the varieties of antidepressant-induced experiences in meditators.
The use of antidepressants continues to increase, yet relatively little is known about their precise subjective effects, and there is growing concern about subtle psychological side effects. One novel investigative approach to these problems may be to use introspectively trained subjects such as meditators. Experienced meditators recently taking antidepressants rated antidepressant effects on multiple dimensions of experience and reported significant emotional, motivational, and cognitive effects and benefits. This study suggests that a) meditators may benefit both clinically and meditatively from antidepressants, b) meditators may provide significant novel information on antidepressant effects, c) meditators may prove valuable for phenomenological investigations of psychopathology, drug effects, and therapies, d) meditation may prove a helpful maintenance therapy for depression, and e) enhanced equanimity may contribute to the broad therapeutic efficacy of antidepressants.


The Integrity of the HMR complex is necessary for centromeric binding and reproductive isolation in Drosophila.
Postzygotic isolation by genomic conflict is a major cause for the formation of species. Despite its importance, the molecular mechanisms that result in the lethality of interspecies hybrids are still largely unclear. The genus Drosophila, which contains over 1600 different species, is one of the best characterized model systems to study these questions. We showed in the past that the expression levels of the two hybrid incompatibility factors Hmr and Lhr diverged in the two closely related Drosophila species, D. melanogaster and D. simulans, resulting in an increased level of both proteins in interspecies hybrids. The overexpression of the two proteins also leads to mitotic defects, a misregulation in the expression of transposable elements and decreased fertility in pure species. In this work, we describe a distinct six subunit protein complex containing HMR and LHR and analyse the effect of Hmr mutations on complex integrity and function. Our experiments suggest that HMR needs to bring together components of centromeric and pericentromeric chromatin to fulfil its physiological function and to cause hybrid male lethality.


Distal Junctional Disease after Occipitothoracic Fusion for Rheumatoid Cervical Disorders: Correlation with Cervical Spine Sagittal Alignment.
Study Design Retrospective radiographic study. Objective We have performed occipitothoracic (OT) fusion for severe rheumatoid cervical disorders since 1991. In our previous study, we reported that the distal junctional disease occurred in patients with fusion of O-T4 or longer due to increased mechanical stress. The present study further evaluated the association between the distal junctional disease and the cervical spine sagittal alignment. Methods Among 60 consecutive OT fusion cases between 1991 and 2010, 24 patients who underwent O-T5 fusion were enrolled in this study. The patients were grouped based on whether they developed postoperative distal junctional disease (group F) or not (group N). We measured pre- and postoperative O-C2, C2-C7, and O-C7 angles and evaluated the association between these values and the occurrence of distal junctional disease. Results Seven (29%) of 24 patients developed adjacent-level vertebral fractures as distal junctional disease. In group F, the mean pre- and postoperative O-C2, C2-C7, and O-C7 angles were 12.1 and 16.8, 7.2 and 11.2, and 19.4 and 27.9 degrees, respectively. In group N, the mean pre- and postoperative O-C2, C2-C7, and O-C7 angles were 15.9 and 15.0, 4.9 and 5.8, and 21.0 and 20.9 degrees, respectively. There were no significant differences between the two groups. The difference in the O-C7 angle (postoperative angle - preoperative angle) in group F was significantly larger than that in group N (p = 0.04). Conclusion Excessive correction of the O-C7 angle (hyperlordotic alignment) is likely to cause postoperative distal junctional disease following the OT fusion.


A review of cervical cancer occurrences in New Zealand 2008-2012.
A review of the screening histories of women/wahine diagnosed with cervical cancer was undertaken to assess where the screening pathway can be improved. Women diagnosed with confirmed or possible cervical cancer during 1 January 2008-31 December 2012 were identified from the National Cancer Registry (NCR) records. Screening histories for these women were obtained from the National Cervical Screening Programme (NCSP) Register along with pathology and cytology reports and staging information. Women aged 25-69 years with confirmed cervical cancer underwent a review of their screening history. Cervical cancer incidence rates were calculated using Statistics New Zealand mid-year population estimates. Seven hundred and seventy-two confirmed diagnoses of cervical cancer were made during 2008-2012 for an incidence rate of 6.9 per 100,000 women per year. Only 13% of 644 women aged 25-69 years had regular cervical cancer screening according to New Zealand guidelines and this proportion was lower among Māori and Pacific people and those living in deprived areas. However, 37% of women had had a screen in the preceding three-year screening interval, excluding screens undertaken within six months of histological diagnosis. In addition, a significant number developed cancer following an abnormal screen. Ongoing efforts are required to improve uptake of regular cervical screening particularly for Māori and socio-economically disadvantaged women/wahine. Further investigation of incident cervical cancers using population-linked data, slide reviews of screens reported as negative and more clinical information is needed to facilitate clinical pathway review to determine the contributing factors that lead to the development of cervical cancer following normal and abnormal screening tests.


E-cigarettes and Western Diet: Important Metabolic Risk Factors for Hepatic Diseases.
The use of electronic nicotine delivery systems (ENDS), also known as e-cigarettes, with a variety of e-liquids/e-juices, is increasing at an alarming rate among adolescents who do not realize the potential harmful health effects. This study examines the harmful effects of ENDS on the liver. Apolipoprotein E null (ApoE-/-) mice on a western diet (WD) were exposed to saline or ENDS with 2.4% nicotine aerosol for 12 weeks using our mouse ENDS exposure model system, which delivers nicotine to mice and leads to equivalent serum cotinine levels found in human cigarette users. ApoE-/- mice on a WD exposed to ENDS exhibited a marked increase in hepatic lipid accumulation compared with ApoE-/- on a similar diet exposed to saline aerosol. The detrimental effects of ENDS on hepatic steatosis were associated with significantly greater oxidative stress, increased hepatic triglyceride levels, and increased hepatocyte apoptosis, independent of adenosine monophosphate-activated protein kinase signaling. In addition, hepatic RNA sequencing analysis revealed that 433 genes were differentially expressed in ENDS-exposed mice on WD compared with saline-exposed mice. Functional analysis indicates that genes associated with lipid metabolism, cholesterol biosynthesis, and circadian rhythm were most significantly altered in the liver in response to ENDS. Conclusion: These results demonstrate profound adverse effects of ENDS on the liver. This is important information for regulatory agencies as they regulate ENDS.


Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor.
Lymphatic vessels develop from specialized venous endothelial cells. Using knockout mice, we found that fasting-induced adipose factor (Fiaf) is required for functional partitioning of postnatal intestinal lymphatic and blood vessels. In wild-type animals, levels of intestinal Fiaf expression rise during the first postnatal day and peak at day 2, which coincides with the onset of the lymphatico-venous partitioning abnormality in Fiaf-/- mutants on a mixed 129/SvJ:C57BL/6 genetic background. Fiaf deficiency is not associated with disruption of the blood vasculature or with lymphatic endothelial recruitment of smooth muscle cells. We identified Prox1, a critical regulator of lymphangiogenesis, as a downstream target for Fiaf signaling in the intestinal lymphatic endothelium. This organ-specific lymphovascular abnormality can be rescued by allowing embryonic Fiaf-/- intestinal isografts to develop in Fiaf+/+ recipients.