Human papillomavirus (HPV) vaccine utilization among adults (18-29 years), BRFSS 2015.
Human papillomavirus (HPV) vaccination acceptance is hampered by fears and conflicting attitudes about the need for and safety of vaccine. There are also ethical dilemmas associated with vaccinating adolescents for a sexually transmitted disease despite future cancer risk. The purpose of this research was to determine HPV vaccination acceptance/hesitancy among young adults. Behavioral Risk Factor Surveillance System 2015 data were used. During 2015, 83.1% of adults ages 25-29 years did not receive any HPV vaccination; the UOR was 3.47; 95% CI = 2.11, 5.70) compared to adults 18-24 years. There is a need to accelerate public health messaging/campaigns to increase HPV vaccination rates.


Prevention of pericardial adhesions with dextran 70.
Pericardial adhesions pose a major problem during reoperative cardiac surgical procedures. The purpose of this study was to determine the effect of intrapericardial dextran 70 on the formation of pericardial adhesions in an animal model. The data obtained revealed that intrapericardial dextran 70 reduced the incidence of experimental pericardial adhesions.


Thyrotropin-releasing hormone (protirelin) inhibits potassium-stimulated glutamate and aspartate release from hippocampal slices in vitro.
Excess excitatory amino acid release is involved in pathways associated with seizures and neurodegeneration. Thyrotropin-releasing hormone (TRH; protirelin), a brain-derived tripeptide, has shown efficacy in the treatment of such disorders, yet its mechanism of neuroprotection is poorly understood. Using superfused hippocampal slices, we tested the hypothesis that TRH could inhibit evoked glutamate/aspartate release in vitro. Rat hippocampal slices were first equilibrated in oxygenated Krebs buffer (KRB) (120 min) then superfused for 10 min with KRB (control), or KRB containing 0.1, 1, or 10 microM TRH respectively, prior to and during 5 min depolarization with high potassium KRB (50 mM [K(+)] +/- TRH). Fractions (1 min) were collected during the 5 min stimulation and for an additional 10 min thereafter and analyzed for glutamate and aspartate by HPLC. TRH had no effect on baseline glutamate/aspartate release, while all three TRH doses significantly (P < 0.05) inhibited peak 50 mM [K(+)]-stimulated glutamate/aspartate release, and glutamate remained below control (P < 0.05) at 15 min post stimulation. A 5 min pulse of TRH (10 microM) had no affect on basal glutamate/aspartate release, whereas the TRH pre-pulsed slices failed to release glutamate/aspartate by [K(+)]-stimulation given 15 min later. These results are the first to show a potent and prolonged inhibitory effect of TRH on evoked glutamate/aspartate release in vitro. These initial studies suggest that exogenous and/or endogenous TRH may function, in part, to modulate excess glutamate release in specific CNS loci. Additional studies are in progress to fully understand the mechanism of this potent effect of TRH and its implication in various CNS disorders.


Enhanced spectral resolution by high-dimensional NMR using the filter diagonalization method and "hidden" dimensions.
High-dimensional (HD) NMR spectra have poorer digital resolution than low-dimensional (LD) spectra, for a fixed amount of experiment time. This has led to "reduced-dimensionality" strategies, in which several LD projections of the HD NMR spectrum are acquired, each with higher digital resolution; an approximate HD spectrum is then inferred by some means. We propose a strategy that moves in the opposite direction, by adding more time dimensions to increase the information content of the data set, even if only a very sparse time grid is used in each dimension. The full HD time-domain data can be analyzed by the filter diagonalization method (FDM), yielding very narrow resonances along all of the frequency axes, even those with sparse sampling. Integrating over the added dimensions of HD FDM NMR spectra reconstitutes LD spectra with enhanced resolution, often more quickly than direct acquisition of the LD spectrum with a larger number of grid points in each of the fewer dimensions. If the extra-dimensions do not appear in the final spectrum, and are used solely to boost information content, we propose the moniker hidden-dimension NMR. This work shows that HD peaks have unmistakable frequency signatures that can be detected as single HD objects by an appropriate algorithm, even though their patterns would be tricky for a human operator to visualize or recognize, and even if digital resolution in an HD FT spectrum is very coarse compared with natural line widths.


Towards effective dietary counseling: a scoping review.
The aim of this scoping review was to identify and map available evidence concerning counseling strategies that contribute to effective DC. Following the PRISMA SCR-Scoping Reviews Statement and Checklist, a systematic search in electronic databases was performed in March 2020. Synthesis of recurring themes in the 28 included studies revealed seven core counseling strategies that effectively contribute to DC: 1) connecting to motivation, 2) tailoring the modality of DC, 3) providing recurring feedback, 4) using integrated dietetic support tools, 5) showing empathy, 6) including clients' preferences, wishes, and expectations during decision-making, and 7) dietitians having high self-efficacy. Multiple counseling strategies contributing to effective DC have been identified and mapped. The counseling strategies identified seem to interrelate, and their conceived interrelatedness reveals that strategies can both compliment or contrast each other. Therefore, advancing effective DC requires further development towards an integrated approach to DC that includes combinations of strategies that form a unified whole. Insights from this scoping review provide a foundation for dietitians to effectively carry out DC and serve as a starting point to further work towards effective DC.


The medicinal plants in the control of tuberculosis: Laboratory study on medicinal plants from the Northern Area of Pakistan.
Tuberculosis (TB) ranks as the second leading cause of deaths due to infectious diseases. Although global efforts have been made to control TB, still, this is a serious threat as Mycobacterium tuberculosis (MTB) produced resistance against both the first- and second-line drugs. The increasing incidence of multidrug-resistant, extremely drug resistant, and totally drug-resistant TB worldwide requires extra efforts to search for new anti-TB drugs. The present study evaluated the antimycobacterial activities of Citrullus colocynthis, Calotropis procera, Ricinus communis, Capparis decidua, and Fagonia cretica plants' extracts against rifampicin-sensitive (H37Rv) and rifampicin-resistant (TMC331) strains of MTB. Out of 44 extracts, 19 extracts were found active against H37Rv sensitive strain. Highest activities were observed in chloroform extract of C. colocynthis (leaves) and n-hexane extract of R. communis (seeds) with minimum inhibitory concentration values of 2.5 mg/ml each. Results show antimycobacterial potential in some of the fractions of studied plants that may be utilized further for isolation of active compounds and as a possible cure against TB.


An efficient method to detect series of fraudulent identity documents based on digitised forensic data.
Document fraud is a transnational form of crime, and its serial character has already been highlighted. To combat this phenomenon, the Interstate Database of Fraudulent Identity Documents (BIDIF) has been created and implemented in Switzerland. It supports the comparison of documents and the detection of series, i.e., documents that share a common source. To efficiently use such a system, forensic document examiners would benefit from a harmonised and proven profiling method. Thus, the aim of this study is to develop a method for comparing documents and establishing series. The method is meant to improve the detection capabilities of forensic document examiners operating BIDIF or engaged in the profiling of fraudulent documents. First, a method based on the visual characteristics of digitised images of fraudulent identity documents has been developed. Subsequently, the method was qualitatively and quantitatively evaluated using four tests. The first test verified the ability of the method to detect pre-existing series. The second test checked the capability of the method to detect links amongst isolated documents. Finally, two further tests were carried out to compare the method impact on the successful detection of series. These tests were carried out by professional forensic document examiners and Master students in forensic science, respectively. This allowed a comparison of the method influence on series detection. The method allowed a significant increase in the number of series and links detected, while also decreasing the occurrence of false negatives and false positives. Furthermore, links were more rapidly detected.


Advancements in the understanding of PTSD and suicide risk: Introduction to a special section.
Individuals with elevated symptoms of posttraumatic stress disorder (PTSD) or a PTSD diagnosis are at increased risk of thinking about, attempting, and dying by suicide. Yet, there remain key gaps in the field's understanding of the relation between PTSD and suicidal thoughts and behaviors. In response, Psychological Trauma: Theory, Research, Practice, and Policy organized this Special Section on PTSD and Suicide Risk. The articles included in this Special Section represent innovations in the understanding of the link between PTSD and suicidality across various at-risk populations and units of analysis. This Special Section additionally contains articles that address key data analytic and assessment considerations, paving the way for methodologically rigorous future research. Ultimately, it is my hope and belief that advancements in the scientific understanding of PTSD and suicide risk will contribute to decreases in suffering and decreases in suicide deaths.


Primary lymphocytic lymphoma of lacrimal gland.
We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered.


Excessive antibiotic use in men with prostatitis.
Prostatitis accounts for 2 million outpatient visits annually. The majority of prostatitis cases fit the definition of chronic pelvic pain syndrome, for which routine antibiotic use is not indicated. Inpatient, outpatient, and pharmacy datasets from the Veterans Health Administration were used to quantify the magnitude of antibiotic use attributable to chronic pelvic pain syndrome. Specifically, men with a diagnosis of infectious/acute prostatitis or a urinary tract infection were excluded, and the remaining men with a diagnosis of prostatitis were defined as having chronic pelvic pain syndrome. The annual prevalence of chronic pelvic pain syndrome was 0.5%. Prescriptions for fluoroquinolone antibiotics were filled in 49% of men with a diagnosis of chronic pelvic pain syndrome compared with 5% in men without chronic pelvic pain syndrome. Men with chronic pelvic pain syndrome were more than 7 times more likely to receive a fluoroquinolone prescription independently of age, race/ethnicity, and comorbid conditions. Increased use of other antibiotics also was observed. High use was similar in men with either infectious/acute prostatitis or chronic pelvic pain syndrome. Despite evidence that antibiotics are not effective in the majority of men with chronic pelvic pain syndrome, they were prescribed in 69% of men with this diagnosis. Some increased use is probably due to uncontrolled confounding by comorbid conditions or inaccurate diagnostic coding. However, a 7-fold higher rate of fluoroquinolone usage suggests that strategies to reduce unnecessary antibiotic use in men with prostatitis are warranted.


Nutritional evaluation of new alternative types of dog foods including raw and cooked homemade-style diets.
New alternative types of pet foods such as raw and cooked homemade-style diets containing human food ingredients have been introduced due to a trend of pet humanization and diversification of consumer needs. To evaluate nutritional adequacy of new alternative types of dog foods containing human food ingredients as maintenance diets for dogs. Eleven homemade-style foods for adult dogs were purchased from online channel in Korea and analyzed to evaluate nutritional adequacy for adult dogs. Nutrients analyzed included crude protein, amino acids, crude fat, fatty acids, and minerals. Crude protein and amino acids in all products satisfied Association of American Feed Control Officials (AAFCO) requirements. Crude fat in one of 11 products did not meet AAFCO requirements. The most deficient minerals were selenium (10 of 11, 90.9%), copper (five of 11, 45.5%), zinc (five of 11, 45.5%), potassium (three of 11, 27.3%), calcium (three of 11, 27.3%), iron (two of 11, 18.2%), and magnesium (one of 11, 9.1%). Six products were not in the range of the recommended Ca:P ratio in AAFCO dog food maintenance nutrient profiles. This study performed nutritional evaluation of raw and cooked homemade-style foods as maintenance diets for adult dogs. Some nutritional inadequacies were observed including some minerals, Ca:P ratio, and omega-6:omega-3 fatty acid ratio, although three products (26.2%) satisfied the AAFCO standard except selenium. Overall, the data suggest a need for accurate nutritional adequacy statement for consumers based on proper methods to validate the formula.


Laparoscopic transversus abdominis release for complex ventral hernia repair: technique and initial findings.
The open Rives-Stoppa retrorectus and transversus abdominis release (TAR) techniques are well established in open ventral and incisional hernia repair. The principles are currently being translated into minimally invasive surgery with different concepts. In this study, we investigate our initial results of transperitoneal laparoscopic TAR for ventral incisional hernia repair (laparoscopic TAR). Over a 20-month period, 23 consecutive patients with incisional hernias underwent surgery. Laparoscopic TAR was performed transperitoneally with adhesiolysis from the anterior abdominal wall, development of the retrorectus space and TAR, midline reconstruction and extraperitoneal mesh reinforcement. There were 23 incisional hernias, of which 70% were M2-M4 and 60% were W3. Median patient age was 68 years and the median BMI was 31. Median operating time was 313 min, and hospital stay was 4 days. Morbidity was 26% (Clavien-Dindo 1: n = 4 and 2 + 3b: n = 2). With the laparoscopic TAR, it was possible to treat a series of patients with ventral incisional hernias. The operating times were long. However, with a low rate of perioperative complications the hospital stay was short As feasibility is demonstrated, the clinical relevance of the method has to be further evaluated.


Evaluating the mutagenicity of the water-soluble fraction of air particulate matter: A comparison of two extraction strategies.
Many studies have focused on assessing the genotoxic potential of the organic fraction of airborne particulate matter. However, the determination of water-soluble compounds, and the evaluation of the toxic effects of these elements can also provide valuable information for the development of novel strategies to control atmospheric air pollution. To determine an appropriate extraction method for assessing the mutagenicity of the water-soluble fraction of PM, we performed microwave assisted (MW) and ultrasonic bath (US) extractions, using water as solvent, in eight different air samples (TSP and PM10). Mutagenicity and extraction performances were evaluated using the Salmonella/microsome assay with strains TA98 and TA100, followed by chemical determination of water-soluble metals. Additionally, we evaluated the chemical and biological stability of the extracts testing their mutagenic potential and chemically determining elements present in the samples along several periods after extraction. Reference material SRM 1648a was used. The comparison of MW and US extractions did not show differences on the metals concentrations, however positive mutagenic responses were detected with TA98 strain in all samples extracted using the MW method, but not with the US bath extraction. The recovery, using reference material was better in samples extracted with MW. We concluded that the MW extraction is more efficient to assess the mutagenic activity of the soluble fraction of airborne PM. We also observed that the extract freezing and storage over 60 days has a significant effect on the mutagenic and analytical results on PM samples, and should be avoided.


[Temperature changes in the mouth and pharyngeal mucosa during alternating cold and warm footbaths].
Cold and changing (warm/cold) footbaths in a curative dosage, used in physiotherapy, at first have the effect of constantly elevating the temperature of the oral and oropharyngeal mucosa. With longer duration and overdosage of the cold irrigation, a steep decrease of the mucosa temperature ensues. The extent of this reaction is determined by circadian variations. The importance of the elevation of the temperature of the mucosa is discussed with reference to resistance against infections from the common cold.


The effect of an additive containing three Lactobacillus species on the fermentation pattern and microbiological status of silage.
Appropriate combinations of lactic acid bacteria (LAB) strains should be selected to optimize the ensiling process, and the additives should be adjusted to the ensiled forage crops. The aim of this study was to determine the effect of inoculation with three Lactobacillus species on the chemical parameters and microbiological quality (beneficial and harmful microbiota) of grass silage. Three species: L. paracasei (LPa), L. brevis (LB) and L. plantarum (LPl), isolated from sugar beet silage and characterized based on 16S rDNA sequences and biochemical parameters, were analyzed in the study. Single strains and their combinations were used as silage inoculants. The basic chemical and microbiological (qPCR) parameters of silages were determined. Based on the results of agglomerative hierarchical clustering (AHC) and principal component analysis (PCA) it was determined that silages inoculated with single LAB strains and LPa + LB and commercial additive (0+) were the best quality ones, particularly with regard to microbiological parameters and they effectively lowered the pH value. A consortium of three Lactobacillus species had no influence on silage quality, whereas LPa + LB and LPl + LB combinations as well as a commercial additive exerted positive effects. Inoculation inhibited the growth of toxin-producing fungi. Only the appropriate LAB composition can improve the quality of the ensiled material (antagonistic relationship). Only the LPa + LB combination was able to improve the value of low dry silage; nevertheless, almost all combinations were able to reduced concentrations of toxin-producing fungi. © 2019 Society of Chemical Industry.


Leg dysfunctions in a hatched chick model of spina bifida aperta.
We created chicks with spina bifida aperta (SBA) by incising the roof plate of the neural tube of embryos at Hamburger and Hamilton stage 18 or 19. Incision over the length of three somites caused spina bifida occulta (SBO)-like malformation in 47% of the hatchlings. Incision over the length of five and seven somites caused SBA-like malformation in 100% of the hatchlings. The SBO chicks exhibited no symptoms, whereas the SBA chicks exhibited paralysis of a leg muscle and imbalance between an agonist and an antagonist leg muscles. Lesions in these SBA chicks were located in the spinal segments that give rise to motor neurons that innervated the dysfunctional muscles. Histological analysis revealed that there were fewer small spinal neurons (interneurons) at the site of the lesion in SBA chicks than in the normal chicks and that there was no such difference in the number of the large spinal neurons (motor neurons). Leg dysfunctions in this model of SBA may be attributable to the smaller number of interneurons in the spinal segments that contain motor neurons that innervate the dysfunctional muscle. This model may facilitate studies of the pathological mechanisms that lead to leg dysfunctions in SBA chicks.


Polyhydric alcohol protective effect on Rhizomucor miehei lipase deactivation enhanced by pressure and temperature treatment.
The influence of polyhydric alcohols (sorbitol, xylitol, erythritol, glycerol) on the thermal stability of Rhizomucor miehei lipase has been studied at high hydrostatic pressure (up to 500 MPa). In the absence of additives, a protective effect (PE) (the ratio between the residual activities determined at 480 MPa for the enzyme in the presence or absence of polyhydric alcohols) of low-applied pressures (from 50 MPa to 350 MPa) against thermal deactivations (at 50 degrees C and 55 degrees C) has been noticed. In the presence of additives, a strong correlation between PE and the total hydroxyl group concentration has been obtained, for the first time, under treatments of combining denaturing temperatures and high hydrostatic pressures. This relationship does not seem to be dependent on the nature polyhydric alcohols as the same effect could be observed with 1 M sorbitol and 2 M glycerol. This PE, against thermal and high pressure combined lipase deactivation, increases with polyhydric alcohol concentrations, and when temperature increases from 25 degrees C to 55 degrees C.


Modulation of attention during visual masking in schizophrenia.
Schizophrenia patients consistently demonstrate performance deficits on visual masking procedures. The present study examined whether attentional manipulation would improve subjects' performance on visual masking. A metacontrast task was administered to 105 schizophrenia patients and 52 healthy comparison subjects. Attention was manipulated by associating selected trials of the task with monetary reward. Schizophrenia patients exhibited poorer performance than the comparison subjects across conditions. Patients demonstrated modest, but statistically significant, improvement in performance with the attentional manipulation. This improvement was not significant for the comparison subjects. These findings suggest that early visual processes in schizophrenia are responsive to attentional manipulation but that the degree of improvement is relatively small, suggesting that these processes are not easily altered.


Spontaneously emerging direction selectivity maps in visual cortex through STDP.
It is still an open question as to whether, and how, direction-selective neuronal responses in primary visual cortex are generated by feedforward thalamocortical or recurrent intracortical connections, or a combination of both. Here we present an investigation that concentrates on and, only for the sake of simplicity, restricts itself to intracortical circuits, in particular, with respect to the developmental aspects of direction selectivity through spike-timing-dependent synaptic plasticity. We show that directional responses can emerge in a recurrent network model of visual cortex with spiking neurons that integrate inputs mainly from a particular direction, thus giving rise to an asymmetrically shaped receptive field. A moving stimulus that enters the receptive field from this (preferred) direction will activate a neuron most strongly because of the increased number and/or strength of inputs from this direction and since delayed isotropic inhibition will neither overlap with, nor cancel excitation, as would be the case for other stimulus directions. It is demonstrated how direction-selective responses result from spatial asymmetries in the distribution of synaptic contacts or weights of inputs delivered to a neuron by slowly conducting intracortical axonal delay lines. By means of spike-timing-dependent synaptic plasticity with an asymmetric learning window this kind of coupling asymmetry develops naturally in a recurrent network of stochastically spiking neurons in a scenario where the neurons are activated by unidirectionally moving bar stimuli and even when only intrinsic spontaneous activity drives the learning process. We also present simulation results to show the ability of this model to produce direction preference maps similar to experimental findings.


Superoxide generated by glutathione reductase initiates a vanadate-dependent free radical chain oxidation of NADH.
Vanadate V(V) markedly stimulated the oxidation of NADPH by GSSG reductase and this oxidation was accompanied by the consumption of O2 and the accumulation of H2O2. Superoxide dismutases completely eliminated this effect of V(V), whereas catalase was without effect, as was exogenous H2O2 added to 0.1 mM. These effects could be seen equally well in phosphate- or in 4-(2-hydroxyethyl)1-piperazineethanesulfonic acid-buffered solutions. Under anaerobic conditions there was no V(V)-stimulated oxidation of NADPH. Approximately 4% of the electrons flowing from NADPH to O2, through GSSG reductase, resulted in release of O2-. The average length of the free radical chains causing the oxidation of NADPH, initiated by O2- plus V(V), was calculated to be in the range 140-200 NADPH oxidized per O2- introduced. We conclude that GSSG reductase, and by extension other O2(-)-producing flavoprotein dehydrogenases such as lipoyl dehydrogenase and ferredoxin reductase, catalyze V(V)-stimulated oxidation of NAD(P)H because they release O2- and because O2- plus V(V) initiate a free radical chain oxidation of NAD(P)H. There is no reason to suppose that these enzymes can act as NAD(P)H:V(V) oxidoreductases.


Evaluation of the potential of Trichoderma viride in the control of fungal pathogens of Roselle (Hibiscus sabdariffa L.) in vitro.
The potential of Trichoderma viride as a bio-control agent was evaluated in vitro against Roselle pathogens i.e. Phoma exigua, Fusarium nygamai and Rhizoctonia solani[1] using the dual culture technique. Volatile and non-volatile inhibitors of Trichoderma were also evaluated for this purpose. T. viride[2] was shown to have a marked inhibitory effect on the tested pathogens in vitro. Maximum inhibition occurred against P. exigua, with 71.76% reduction in mycelial radial growth. The three pathogens, P. exigua, F. nygamai and R. solani were also found to be susceptible to the volatile inhibitors produced by T. viride, giving rise to growth inhibition of about 68% in each case. When T. viride non-volatile metabolites were tested against the pathogens, maximum inhibition occurred against R. solani (73.95% mycelial growth inhibition), followed by P. exigua (37.17% inhibition). The inhibitory effect of the non-volatile metabolites on F. nygamai was, however, minimal.


HDAC4 degradation by combined TRAIL and valproic acid treatment induces apoptotic cell death of TRAIL-resistant head and neck cancer cells.
Although TRAIL can directly induce cell death in some cancer cells, it appears that TRAIL resistance exists in many cancers. This study focuses on anti-cancer drugs for TRAIL-resistant head and neck cancer (HNC) to provide further progress toward effective cancer therapy. Results indicate in TRAIL-resistant HNC cells, that combined TRAIL and VPA treatment greatly reduced cell viability and therefore induced cell death, relative to treatment with TRAIL or VPA alone. A caspase-dependent signaling pathway was demonstrated, and combined treatment with TRAIL and VPA also significantly decreased the expression of HDAC4. When we pretreated cells with z-VAD followed by combined treatment with TRAIL and VPA, cell death was blocked with no reduction in expression of HDAC4. To confirm that cell death involved HDAC4 in HNC cells, we knocked down expression of HDAC4 with siRNA, followed by treatment with TRAIL and VPA. Results showed that loss of HDAC4 sensitized the TRAIL-resistant HNC cells to apoptotic cell death. Finally, we showed elevated expression of HDAC4 in HNC tissues compared to normal tissues obtained from the same patients. In conclusion, we suggest that combined VPA and TRAIL treatment may be a promising therapy for HNC via HDAC4 degradation.


Emergency medical services for children and pediatric trauma system components.
The concept of an emergency medical service for children (EMS-C) is new. Although adult EMS systems exist in every region of the United States, the needs of the child suffering from acute injury or illness have not been previously addressed. The development and incorporation of an EMS-C system into the existing adult EMS system is the most time- and cost-effective method to achieve efficient care for the acutely injured or ill child. The components of an EMS-C system include system design, education, prevention, standards of care, research and development, quality assurance, and funding.


Supramolecular tailoring of protein-nanoparticle interactions using cucurbituril mediators.
Supramolecular modification of nanoparticle surfaces through threading of cucurbit[7]uril (CB[7]) onto surface ligands is used to regulate protein-nanoparticle interactions.


ENLARGEMENT OF FOVEAL AVASCULAR ZONE IN DIABETIC EYES EVALUATED BY EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
To evaluate the area of the foveal avascular zone (FAZ) detected by en face OCTA (AngioVue, Avanti OCT; Optovue) in healthy and diabetic eyes. Retrospective chart review of patients who underwent fundus examination including en face OCTA. Eyes with proliferative diabetic retinopathy and history of laser photocoagulation were excluded. The FAZ area in the superficial and deep plexus layers were measured and evaluated using ImageJ software. The FAZ area in the superficial layer was 0.25 ± 0.06 mm² in healthy eyes (n = 19), whereas it was 0.37 ± 0.07 mm² in diabetic eyes without retinopathy (n = 24) and 0.38 ± 0.11 mm² in eyes with diabetic retinopathy (n = 20). Diabetic eyes showed statistically significant FAZ enlargement compared with healthy eyes, regardless of the presence of retinopathy (P < 0.01). The FAZ area in the deep plexus layer was also significantly larger in diabetic eyes than in healthy eyes (P < 0.01). Our data suggest that diabetic eyes show retinal microcirculation impairment in the macula even before retinopathy develops. En face OCTA is a useful noninvasive screening tool for detecting early microcirculatory disturbance in patients with diabetes.


The Gamblers Treatment Clinic of St. Vincent's North Richmond Community Mental Health Center: characteristics of the clients and outcome of treatment.
Data were analyzed from gamblers treated as outpatients: 128 for whom admission data were available and 88 for whom both admission and termination data were available. This group consisted mostly of White males. The average age of the clients was about 42 years. These clients were frequent and heavy bettors whose lives were deeply disrupted by gambling. The clients reported significantly less gambling at termination of treatment than they did at initiation. Improvements in social relations were reported at termination of treatment. There was some evidence that improvements in life-style were related to reports of less gambling at termination of treatment.


ATP competitive inhibitors of D-alanine-D-alanine ligase based on protein kinase inhibitor scaffolds.
D-Alanine-D-alanine ligase (DDl) is an essential enzyme in bacterial cell wall biosynthesis and an important target for developing new antibiotics. Here, we describe a new approach to identify new inhibitor scaffolds for DDl based on similarity in the ATP binding region of different kinases and DDl. After an initial screening of several protein kinase inhibitors, we found that the Brutons's tyrosine kinase inhibitor LFM-A13, an analog of the Leflunomide metabolite A771726, inhibits DDl with a K(i) of 185 microM. A series of malononitrilamide and salicylamide derivatives of LFM-A13 has been synthesized to confirm the validity of this scaffold as an inhibitor of DDl.


'A German Whore and no Money at that': Insanity and the Moral and Political Economies of German South West Africa.
While the links between colonial psychiatry and racism figure prominently in histories of the diagnosis, treatment and institutionalisation of the mentally ill in Africa, there is an absence of patient-centred accounts, in the analysis of the efforts of the colonial-era subjects themselves to be pro-active not merely as the mentally ill, by clinical or court definition, but as persons embedded in social relationships with their kin and significant others. Moreover, despite an emerging scholarship, little is known of the experience of European settlers. In this respect there is a need for a more balanced representation, one that shows the ambivalence of colonial psychiatry and its reach into the lives of colonial subjects, Africans and Europeans alike. In this paper I focus on the narratives of a settler in German South West Africa and her efforts to escape diagnosis and institutionalisation. In building on a feminist approach to illness narratives, in particular on the idea of bearing empathic witness, I will explore the ways in which illness narratives can reveal the complex moral and political economies of the colonial world.


Methods for studying prion protein (PrP) metabolism and the formation of protease-resistant PrP in cell culture and cell-free systems. An update.
Transmissible spongiform encephalopathies (TSE) or prion diseases result in aberrant metabolism of prion protein (PrP) and the accumulation of a protease-resistant, insoluble, and possibly infectious form of PrP, PrP-res. Studies of PrP biosynthesis, intracellular trafficking, and degradation has been studied in a variety of tissue culture cells. Pulse-chase metabolic labeling studies in scrapie-infected cells indicated that PrP-res is made posttranslationally from an apparently normal protease-sensitive precursor, PrP-sen, after the latter reaches the cell surface. Cell-free reactions have provided evidence that PrP-res itself can induce the conversion of PrP-sen to PrP-res in a highly species- and strain-specific manner. These studies have shed light on the mechanism of PrP-res formation and suggest molecular bases for TSE species barrier effects and agent strain propagation.


A novel in vitro prognostic model of bladder cancer based on urine-derived living tumor cells.
Bladder cancer (BLCA) remains a difficult malignancy to manage because of its high recurrence, intense follow-up, and invasive diagnostic and treatment techniques. Immune checkpoint inhibitors (ICIs) have forged a new direction for the treatment of BLCA, but it is currently challenging to predict whether an individual patient will be sensitive to ICIs. We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells (BCCs) culturing using our previously reported BCC culture platform. We used flow cytometry (FCM) to measure the expression levels of Programmed Death-Ligand 1 (PD-L1) on BCCs before and after interferon-gamma (IFN-γ) treatment and found that PD-L1 expression and the sensitivities to IFN-γ varied among patients. RNA-sequencing, western blotting, and programmed death-1 (PD-1) binding assays confirmed that the BCC FCM-based PD-L1 detection platform (BC-PD-L1) was reliable and was not hindered by the glycosylation of PD-L1. In the subsequent retrospective study, we found that IFN-γ-stimulated PD-L1 (sPD-L1) expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients. Importantly, the prognostic value was similar or even better in urine-derived BC-PD-L1 (UBC-PD-L1). Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix, cell-cell adhesion, and positive regulation of the immune system. In addition, the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients. In conclusion, as a novel personalized urine-detection method, UBC-PD-L1 may provide a rapid, accurate, and non-invasive tool for monitoring tumor progression, predicting therapeutic responses, and helping improve BLCA clinical treatment in future.


Bioaccumulation of trace elements and hydrocarbons in chondrichthyans of the western Arabian Gulf: Environmental and human health risk assessment and implications for conservation.
This is a first attempt to assess the levels of trace elements, PAHs, and TPHs in six elasmobranch species (Carcharhinus dussumieri, C. sorrah, Chiloscyllium arabicum, Gymnura poecilura, Sphyrna lewini, S. mokarran) from the Arabian Gulf. The chemical analysis showed that the concentrations of contaminants differed significantly between liver and muscle samples with both pelagic and benthic species and all families. For all species, contaminant concentrations were significantly higher in the liver than in the muscle. While muscle contaminant concentrations differed significantly with respect to species' lifestyles and families, those of liver showed no significant differences between pelagic and benthic species, neither between the four families nor between the six species. None of the analysed contaminants exceeded the internationally recognized standards in all studied species. These results enrich the knowledge on the bioaccumulation of contaminants in elasmobranchs and allow to assess the environmental status of the Arabian Gulf.


A composite clinical motor score as a comprehensive and sensitive outcome measure for Parkinson's disease.
An unmet need remains for sensitive outcome measures in neuroprotective trials. The study aims to determine whether a composite clinical motor score, combining the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III motor examination score, Purdue Pegboard Test, and Timed Up and Go, provides greater sensitivity in detecting motor change in early disease than the MDS-UPDRS III alone. The Oxford Discovery longitudinal cohort study involves individuals with isolated rapid eye movement sleep behaviour disorder (iRBD) (n=272, confirmed polysomnographically, median follow-up: 1.6 years), idiopathic Parkinson's disease (PD) (n=909, median follow-up: 3.5 years, baseline: <3.5 years disease duration) and controls (n=316, age-matched and sex-matched, without a first-degree family history of PD). Motor and non-motor assessments were performed at each in-person visit. Compared with the MDS-UPDRS III, the composite clinical motor score demonstrated a wider score distribution in iRBD and controls, lower coefficient of variation (37% vs 67%), and higher correlation coefficients with self-reported measures of motor severity (0.65 vs 0.61) and overall health status (-0.40 vs -0.33). Greater score range in mild to moderate PD, higher magnitude of longitudinal change in iRBD and longitudinal score linearity suggest better sensitivity in detecting subtle motor change. The composite clinical motor score was more accurate than the MDS-UPDRS III in predicting clinical outcomes, requiring 64% fewer participants with PD and 51% fewer participants with iRBD in sample size estimations for a hypothetical 18-month placebo-controlled clinical trial. The composite clinical motor score may offer greater consistency and sensitivity in detecting change than the MDS-UPDRS III.


Efficacy of intensive CBT telehealth for obsessive-compulsive disorder during the COVID-19 pandemic.
Despite evidence for the effectiveness of cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD), many individuals with OCD lack access to needed behavioral health treatment. Although some literature suggests that virtual modes of treatment for OCD are effective, it remains unclear whether intensive programs like partial hospitalization and intensive outpatient programs (PHP and IOPs) can be delivered effectively over telehealth (TH) and within the context of a global pandemic. Limited extant research suggests that clinicians perceive attenuated treatment response during the pandemic. The trajectory and outcomes of two matched samples were compared using linear mixed modeling: a pre-COVID in-person (IP) sample (n = 239) and COVID TH sample (n = 239). Findings suggested that both modalities are effective at treating OCD and depressive symptoms, although the pandemic TH group required an additional 2.6 treatment days. The current study provides evidence that PHP and IOP treatment delivered via TH during the COVID-19 pandemic is approximately as effective as pre-pandemic IP treatment and provides promising findings for the future that individuals with complicated OCD who do not have access to IP treatment can still experience significant improvement in symptoms through TH PHP and IOP treatment during and potentially after the pandemic.


Differential hepatic avoidance radiation therapy: Proof of concept in hepatocellular carcinoma patients.
To evaluate the feasibility of a novel planning concept that differentially redistributes RT dose away from functional liver regions as defined by (99m)Tc-sulphur colloid (SC) uptake on patient SPECT/CT images. Ten HCC patients with different Child-Turcotte-Pugh scores (A5-B9) underwent SC SPECT/CT scans in treatment position prior to RT that were registered to planning CT scans. Proton pencil beam scanning (PBS) therapy plans were optimized to deliver 37.5-60.0Gy (RBE) over 5-15 fractions using single field uniform dose technique robust to range and setup uncertainty. Photon volumetrically modulated arc therapy (VMAT) plans were optimized to the same prescribed dose and minimum target coverage. For both treatment modalities, differential hepatic avoidance RT (DHART) plans were generated to decrease dose to functional liver volumes (FLV) defined by a range of thresholds relative to maximum SC uptake (43-90%) in the tumor-subtracted liver. Radiation dose was redistributed away from regions of increased SC uptake in each FLV by linearly scaling mean dose objectives during PBS or VMAT optimization. DHART planning feasibility was assessed by a significantly negative Spearman's rank correlation (RS) between dose difference and SC uptake. Patient, tumor, and treatment planning characteristics were tested for association to DHART planning feasibility using non-parametric Kruskal-Wallis ANOVA. Compared to conventional plans, DHART plans achieved a 3% FLV dose reduction for every 10% SC uptake increase. DHART planning was feasible in the majority of patients with 60% of patients having RS<-0.5 (p<0.01, range -1.0 to 0.2) and was particularly effective in 30% of patients (RS<-0.9). Mean dose to FLV was reduced by up to 20% in these patients. Only fractionation regimen was associated with DHART planning feasibility: 15 fraction courses were more feasible than 5-6 fraction courses (RS<-0.93 vs. RS>-0.60, p<0.02). Differential avoidance of functional liver regions defined on sulphur colloid SPECT/CT is achievable with either photon VMAT or proton PBS therapy. Further investigation with phantom studies and in a larger cohort of patients may validate the utility of DHART planning for HCC radiotherapy.


Aaron Klug and the revolution in biomolecular structure determination.
Aaron Klug's group was one of the first to use a combination of X-ray diffraction and electron microscopy to study the structures of macromolecules. He helped to provide the intellectual framework for understanding the self-assembly of regular viruses and developed methods for analyzing their three-dimensional structures from electron microscope images, as well as the structures of helical polymers. He and his coworkers established the basic features of chromatin organization, including the structure of the repeating units (nucleosomes) and how they are stacked together. He studied a variety of molecules that interact with DNA or RNA, including disks of tobacco mosaic virus protein, a tRNA and a ribozyme, and also discovered the zinc-finger motif in nucleic acid-binding proteins. Thus, he has played a major part in developing the ideas and techniques that established structural molecular biology as an exciting new science during the second half of the twentieth century.


Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.
The effect of a naturally occurring flavonoid apigenin on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body weight) every other day, and from week 16, s.c. injections of apigenin (0.75 or 1.5 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth patterns and labeling index, it was found to decrease significantly the incidence of cancer metastasis. Apigenin significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but not matrix metalloprotease (MMP)-9 expression. Our findings indicate that apigenin inhibits cancer metastasis through inhibition of phosphorylation of MAPK.


DNA looping and catalysis; the IHF-folded arm of Tn10 promotes conformational changes and hairpin resolution.
DNA loops and bends are common features of DNA processing machines. The bacterial transposon Tn10 has recruited integration host factor (IHF), a site-specific DNA-bending protein, as an architectural component for assembly of the higher-order nucleoprotein complex within which the transposition reaction takes place. Here, we demonstrate additional roles for the IHF loop during the catalytic steps of the reaction. We show that metal ion-dependent unfolding of the IHF-bent transposon arm is communicated to the catalytic center, inducing a substantial conformational change in the DNA. Partial disruption of the IHF loop shows that this step promotes resolution of the hairpin intermediate on one transposon end and initiation of catalysis at the other. Further evidence suggests that the molecular mechanism responsible may be mechanical stress in the IHF loop, related to a change in the relative position of the transposase contacts that anchor the loop on either side.


Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation.
Allergy is the result of a complex immune cascade leading to the dysregulated production of Th2 cytokines, the generation of allergen-specific IgE-producing B cells and the subsequent activation and degranulation of mast cells upon allergen challenge. Dendritic cells (DCs) play an important role in several models of allergy, but factors instructing DCs to induce a dysregulated Th2 response are currently unknown. In this review, we present recent evidence that human thymic stromal lymphopoietin (TSLP), a novel IL-7-like cytokine, might represent an early trigger of the allergic immune cascade. TSLP-activated human DCs produce Th2-attracting chemokines but no IL-12, and induce naive CD4(+) and CD8(+) T cell differentiation into effector cells with a typical pro-allergic phenotype. TSLP is produced by human epithelial, stromal, and mast cells. It is highly expressed by the keratinocytes of atopic dermatitis but not in other types of skin inflammation. Thus, epithelial- and stromal-cell-derived TSLP might represent one of the factors initiating the allergic responses, and could be a target for a curative therapeutic approach to allergy.


Alternative Management of the Capsule in the Bristow-Latarjet Procedure.
The Bristow-Latarjet procedure is considered the current gold standard for the management of anterior glenohumeral joint instability in which significant glenoid bone loss is present, and numerous techniques have been proposed for capsular management after the bony augmentation component of the procedure. These techniques for capsular management include excision of the capsule and labrum, 2-flap elevation, T-capsulotomy, or an L-shaped incision into the capsule. Capsular management during open shoulder procedures may vary among surgeons and may or may not include capsulolabral repair after the Bristow-Latarjet procedure. The purpose of this Technical Note was to illustrate an alternative approach to capsular management, focusing on the elevation of the capsulolabral complex as a sleeve along with augmentation using the coracoacromial ligament during the Bristow-Latarjet procedure in patients with anterior glenohumeral instability. The proposed technique provides the benefit of improvement in visualization to more reliably identify the ideal location for bone block placement and allows for the surgeon to perform a large inferior-to-superior capsular shift to prevent inferior subluxation or instability.


Hippocampal neuron number is unchanged 1 year after fractionated whole-brain irradiation at middle age.
To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of (137)Cs gamma rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus.


Association between High Serum Homocysteine Levels and Biochemical Characteristics in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis.
Elevated homocysteine levels have been observed in previous studies of PCOS; however, the nature of the associations between high homocysteine levels and the biochemical characteristics of polycystic ovarian syndrome (PCOS)-such as obesity, insulin resistance (IR), and androgen levels-is still uncertain. A systematic search was conducted electronically up to December 28, 2015 using specific eligibility criteria. Standardized mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were used as a measure of effect size. A total of 34 studies (with 1,718 cases and 1,399 controls) of homocysteine levels in PCOS were pooled in this meta-analysis. Significantly lower homocysteine levels were found in controls than in PCOS patients (SMD = 0.895, 95% CI = 0.643-1.146, P<0.001; I2 = 90.4% and P<0.001 for heterogeneity), regardless of the degree of obesity, IR, or androgen levels. Homocysteine levels in non-IR PCOS patients were significantly lower than those of PCOS patients with IR (SMD = 0.69, 95% CI = 0.37-1.01, P<0.01; I2 = 0% and P = 0.50 for heterogeneity). However, metformin treatment did not appear to cause any significant change in the homocysteine levels of PCOS patients (SMD = -0.17, 95% CI = -1.10-0.75, P = 0.71; I2 = 92% and P<0.01 for heterogeneity). High homocysteine levels in women with PCOS are not related to degree of obesity, IR, or androgen levels. Metformin treatment cannot decrease the homocysteine levels in PCOS patients.


Recognition of a novel HLA-DRB1*09 variant, HLA-DRB1*09:25, in a Taiwanese hematopoietic stem cell donor.
One nucleotide replacement at codon 91of the HLA-DRB1*09:01:02 results in a novel allele, HLA-DRB1*09:25.


a-b palmar interdigital ridge-count in the Basque population.
The a-b palmar interdigital ridge count was analyzed in a sample of 841 males and 911 females of Basque origin. Bimanual differences were not found, against that a significant sexual dimorphism. The mean ridge count value is in the lower lange of the variability among White populations.


Verifying the Indonesian version of the Child Behavior Checklist.
The Child Behavior Checklist for Ages 6-18 (CBCL/6-18) is widely used to assess emotional and behavioral problems in children in the USA and Europe. Given that Indonesia has a more traditional culture that is different from the USA and Europe, it is possible that the CBCL is not effective in assessing the emotional and behavioral problems of Indonesian children, due to a difference in culture. Moreover, the validity and reliability of the Indonesian version of the CBCL/6-18 have not been tested. The purpose of this study was therefore to test the validity and reliability of the Indonesian version of the CBCL/6-18. Three hundred and eight mothers of children attending public primary schools participated in this study by completing the self-administered questionnaire. All items of the CBCL were positively correlated with total score (0.15-0.59), and total problems score had high internal consistency (r = 0.94). The correlations between questionnaire items and the eight subscales of the CBCL ranged from 0.10 to 0.74 and from 0.12 to 0.64 for the internalizing and externalizing scales, respectively (P < 0.01). The eight subscales of the CBCL had good internal consistency (0.61-0.87). The CBCL/6-18 is a valid and reliable instrument to measure emotional and behavioral problems in Indonesian children aged 6-12 years.


Ultrastructure of alcoholic hyaline filaments in alcoholic hepatitis.
Ultrastructure of alcoholic hyaline (AH) in alcoholic hepatitis was observed to demonstrate the relationship between AH filaments and intermediate filaments (IFs). Type 1, Type 2 and Type 3 AH were noted in hepatocytes, and the filaments in these types of AH showed similar ultrastructural findings as already reported. Two different kinds of filaments were noted in the Type 2 AH. The large on showed 160 to 200 A in a diameter and the small one showed around 100 A in diameter. Of the 29 cases with alcoholic hepatitis, a new type of AH was noted in the rosette forming hepatocytes in 2 cases of alcoholic hepatitis. The filaments of this AH in rosette forming hepatocytes showed 40 to 60 A in diameter and shorter length compared with Type 2 AH. These filaments with 40 to 60 A diameter were quite different from IFs. Our results indicate that AH in alcoholic hepatitis is not induced by the simple accumulation of the IFs.


Race, deprivation, and immigrant isolation: The spatial demography of air-toxic clusters in the continental United States.
This article contributes to environmental inequality outcomes research on the spatial and demographic factors associated with cumulative air-toxic health risks at multiple geographic scales across the United States. It employs a rigorous spatial cluster analysis of census tract-level 2005 estimated lifetime cancer risk (LCR) of ambient air-toxic emissions from stationary (e.g., facility) and mobile (e.g., vehicular) sources to locate spatial clusters of air-toxic LCR risk in the continental United States. It then tests intersectional environmental inequality hypotheses on the predictors of tract presence in air-toxic LCR clusters with tract-level principal component factor measures of economic deprivation by race and immigrant status. Logistic regression analyses show that net of controls, isolated Latino immigrant-economic deprivation is the strongest positive demographic predictor of tract presence in air-toxic LCR clusters, followed by black-economic deprivation and isolated Asian/Pacific Islander immigrant-economic deprivation. Findings suggest scholarly and practical implications for future research, advocacy, and policy.


Subchondral bone overgrowth in the presence of full-thickness cartilage defects in the knee.
Between October 2000 and December 2003, 252 autologous chondrocyte implants were performed in 183 patients. Eighty lesions showed overgrowth of the subchondral bone plate under the chondral lesion, this was termed a "bone boss." Thirty-seven were on the medial femoral condyle (MFC), 18 on the lateral femoral condyle (LFC), 21 in the trochlea and 4 on the patella. There was a statistically significant association between the LFC and "bone boss." The lesions showing this finding were of a larger area (3.4 cm2 and 2.8 cm2 respectively, p=0.006), and had more diffuse chondral changes than lesions without. The patients with a "bone boss" had a tendency to longer duration of symptoms (85.3 months and 64.3 months respectively, p=0.089). The "bone bosses" were resected back to the level of the surrounding subchondral bone prior to implantation. Radiological and clinical follow-up showed no statistical difference between the two groups. A discussion of the possible aetiology of the "bone boss" is made.


Smoking history and pulmonary arterial hypertension: Demographics, onset, and outcomes.
Smoking prevalence and its association with pulmonary arterial hypertension (PAH) outcomes have not been described in patients in the United States. Using the US-based Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), the prevalence, demographics, and outcomes in ever- versus never-smokers with PAH were determined. Ever-smoking status was more prevalent in males (61.7%) than in females (42.9%) enrolled in REVEAL. Ever-smokers were older than never-smokers at the time of PAH diagnosis and REVEAL enrollment. The time to first hospitalization, transplant-free survival, and survival did not differ between ever- and never-smokers overall; however, in newly diagnosed males, ever-smoking was associated with earlier death (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.1-3.0; p = 0.0199), the composite of transplant or death (HR 2.2, 95% CI 1.4-3.6; p = 0.0008), and first hospitalization (HR 1.8, 95% CI 1.2-2.7; p = 0.0063), though smoking exposure (pack-years) did not differ between newly and previously diagnosed males. REVEAL PAH data demonstrate that smoking prevalence in male PAH patients is disproportionate. The prevalence of cigarette smoking was significantly higher in males than females enrolled in REVEAL. Ever-smoking status was associated with increased age at PAH diagnosis and, in newly diagnosed male PAH patients, earlier time to hospitalization and shorter survival after PAH diagnosis.


Recurrence in meningeal hemangiopericytomas.
Meningeal hemangiopericytomas are more aggressive than typical meningiomas, with a high rate of recurrence and distant metastases. The question of whether a correlation exists between prognosis and histologic features remains controversial. We report two cases of recurrent meningeal hemangiopericytomas. Although local growth control of the tumor was obtained by tumor removal and irradiation in a 38-year-old male patient (Case 1) with a recurrent tentorial tumor, the tumor disseminated and metastasized extracranially within a short period after treatment, leading to rapid deterioration. Another 38-year-old female patient (Case 2) with a recurrent orbital tumor had a favorable outcome after tumor removal. The Ki-67 proliferative index using the MIB-1 monoclonal antibody increased as the tumor recurred in Case 1 (2.5%, 7.9%, and 15.7%), but did not change between primary and recurrent tumors of Case 2 (4.2%, 3.1%). Immunostaining for p53 protein in Case 1 was negative at the first resection, and became positive at the second and third resections, whereas in Case 2, it was negative in both the primary and recurrent tumors. Our results suggest that p53 protein accumulation with a high proliferative potential is a useful marker to estimate malignant progression in meningeal hemangiopericytomas.


Photosynthetic and Chlorophyll Fluorescence Characteristics of Isodon rubescens (Hemsley) H. Hara.
The ecological and economic cultivation of Isodon rubescens is currently being carried out. The demand of I. rubescens for light intensity should be made clear to estimate whether the environmental conditions of an area are suitable for cultivating I. Rubescens and improve cultivation techniques. The photosynthetic and chlorophyll fluorescence characteristics of I. rubescens were determined with a Li-6400 photosynthesis system and PAM-2500 portable chlorophyll fluorescence apparatus. The results showed that there was no obvious midday depression of photosynthesis in I. rubescens leaves. The light compensation point and light saturation point of I. rubescens leaves were 21.83482 µmol·m-2·s-1 and 802.262 µmol·m-2·s-1, respectively. The CO2 compensation point and CO2 saturation point of I. rubescens leaves were 101.7199 µmol·mol-1 and 1674.514 µmol·mol-1, respectively. The maximal photochemical efficiency of photosystem II ((Fm-Fo)/Fm) in I. rubescens leaves reached 0.7. The electron transport rate of photosystem II in I. rubescens leaves reached 20 μmol electrons/(m2·s). I. rubescens can tolerate intense light above the light compensation point and utilize low light. I. rubescens leaves have a strong photoprotective capacity. I. rubescens can grow in both sunny and shady places. The most important factor affecting photosynthetic efficiency in I. rubescens leaves is the concentration of CO2 in air.


People with intellectual disabilities and harmful sexual behaviour: Professionals' views on the barriers to prevent harm.
People with intellectual disabilities can be exposed to sexual abuse and they can display harmful sexual behaviour. This study aimed to identify barriers to preventing harmful sexual behaviour in people with intellectual disabilities within the support sector and the justice system. We conducted focus group interviews with 20 participants from hospital-based habilitation centres, community residences, schools and the criminal justice system. The interviews identified a lack of education and guidelines for stakeholders or carers on regulating the sexual behaviour of people with intellectual disabilities. The criminal justice system faces challenges related to prioritising, understanding and communicating. People with intellectual disabilities may lack an understanding of the concepts of sexual consent and acceptable sexual behaviour. There is a need to improve knowledge about intellectual disability and how to prevent harmful sexual behaviour for professional caregivers in the support sector and the criminal justice system.


House dust microbiome and human health risks.
People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.


Lipoprotein (a) is not a metabolic product of other lipoproteins containing apolipoprotein B.
125I-Labeled autologous very low density lipoprotein (VLDL) was injected intravenously into three lipoprotein (a) positive individuals. One other lipoprotein (a) positive subject received 125I-labeled VLDL from a a lipoprotein (a) negative donor. Specific activity of apolipoprotein B in VLDL, low density lipoprotein (LDL) and lipoprotein (a) was measured for 5 days. In the lipoprotein (a) fraction only traces of radioactivity could be detected, which were caused by contamination with labeled LDL. No precursor-product relationship existed between apolipoprotein B in VLDL or LDL and apolipoprotein B in lipoprotein (a). One lipoprotein (a)-positive individual was kept on a fat-free diet for 4 days to prevent chylomicron formation; no change in the serum level of lipoprotein (a) could be detected under these conditions. The data of this study indicate that lipoprotein (a) is not a metabolic product of VLDL or LDL. Also chylomicrons are not likely to play role as a precursor for lipoprotein (a). It is concluded that lipoprotein (a) is synthesized as a separate lipoprotein.


A cast-iron guarantee of ataxia and deafness.
Superficial siderosis of the central nervous system (CNS) is a rare condition that is thought to be caused by repeated subarachnoid haemorrhages. The major clinical features are progressive bilateral hearing loss, cerebellar ataxia and pyramidal dysfunction. Ante-mortem diagnosis is now possible due to MRI and post mortem reports of this condition are becoming rare. Despite the occurrence of typical clinical features the diagnosis is often missed during life if CT scanning alone is performed. We describe a case of superficial siderosis of the CNS with clinical and post mortem findings as a reminder of this unusual condition.


Detection of DNA damage in mouse peripheral blood leukocytes by the comet assay after oral administration of monocrotophos.
The objective of this study was to determine if single/double strand DNA breaks could be induced by monocrotophos (organophosphorus pesticide) in mice in vivo using the comet assay. Mice were dosed orally with 0.046, 0.093, 0.186, 0.373 and 0.746 mg/kg body weight of monocrotophos, and the assay was performed on whole blood after 24, 48 and 72 h. A significant increase in mean comet tail length indicating DNA damage was observed at 24 and 48 h post-treatment with monocrotophos when compared to controls. A decrease in the mean tail length was observed at 72 h post-treatment indicating repair of the damaged DNA. The mean tail length showed a dose-related increase and time dependent decrease. The study reveals that comet assay is a sensitive and rapid method to detect genotoxicity of monocrotophos.


In silico analyses of Wilms׳ tumor protein to designing a novel multi-epitope DNA vaccine against cancer.
Predefined and pre-weighted objective criteria and essential role of Wilms׳ tumor wild type gene (WT1) for maintaining transformed features of cancer cells confirm the high potency of WT1 as a valuable cancer antigen. The antigen was at the top of the ranking among 75 representative cancer antigens. In the present study, an in silico approach was launched to characterized novel CTL epitopes and design a novel multi-epitope DNA vaccine to elicit a desirable immune response against cancers over expressing WT1. Forty-four novel epitopes were described. A multi-epitope construct was designed based on predicted epitopes which is 310 residues in length. The vaccine candidate designed here displays acceptable population coverage (>65%) in different ethnicities as well as high probability of eliciting WT1 antibodies which both are pertinent goals in the context of appropriate multi-epitope vaccines. Various in silico analyses indicate that final vaccine is a qualified immunotherapy candidate capable of eliciting both CD4+ and CD8+ T cell responses.


Ral-GTPases: approaching their 15 minutes of fame.
Andy Warhol, the famous pop artist, once claimed that "in the future everyone will be famous for 15 minutes". The same, it seems, can be said of proteins, because at any given time some proteins become more "fashionable" to study than others. But most proteins have been highly conserved throughout millions of years of evolution, which implies that they all have essential roles in cell biology. Thus, each one will no doubt enter the limelight if the right experiment in the right cell type is done. A good example of this is the Ras-like GTPases (Ral-GTPases), which until recently existed in the shadow of their close cousins--the Ras proto-oncogenes. Recent studies have yielded insights into previously unappreciated roles for Ral-GTPases in intensively investigated disciplines such as vesicle trafficking, cell morphology, transcription and possibly even human oncogenesis.


Purification of BmR1 recombinant protein.
This paper describes a refinement in the purification step that facilitated the downstream recovery of high purity BmR1 recombinant protein, which is a protein used as a test reagent in the commercialized rapid tests for detection of lymphac filariasis i.e. Brugia Rapid™ and panLF rapid™. Purification was performed by immobilized metal affinity chromatography (IMAC), followed by ion exchange chromatography (IEX). Results showed that a total of 10.27 mg of BmR1 was obtained when IMAC was performed using 20 mM of imidazole and 5 column volume of wash buffer containing 500 mM of NaCl. Purity of the target protein was enhanced when buffer at pH 5.8 was used during the IEX. Two proteins that recurrently appeared below the BmR1 recombinant protein were identified by mass-spectrometry analysis as the same protein, thus they were probably degradation products of BmR1. These strategies improve purity of the target protein to be used in applications such as production of aptamers and monoclonal antibodies.


Characterization of Key Odorants in Scallion Pancake and Investigation on Their Changes during Storage.
To characterize key odorants in scallion pancake (SP), volatiles were extracted by solvent extraction-solvent assisted flavor evaporation. A total of 51 odor-active compounds were identified by gas chromatography-olfactometry (GC-O) and chromatography-mass spectrometry (GC-MS). (Z/E)-3,6-Diethyl-1,2,4,5-tetrathiane was detected for the first time in scallion food. Application of aroma extract dilution analysis to extracts showed maltol, methyl propyl disulfide, dipropyl disulfide and 2-pentylfuran had the highest flavor dilution (FD) factor of 4096. Twenty-three odorants with FD factors ≥ 8 were quantitated, and their odor active values (OAVs) were calculated. Ten compounds with OAVs ≥ 1 were determined as the key odorants; a recombinate model prepared from the key odorants, including (E,E)-2,4-decadienal, dimethyl trisulfide, methyl propyl disulfide, hexanal, dipropyl trisulfide, maltol, acetoin, 2-methylnaphthalene, 2-pentylfuran and 2(5H)-furanone, successfully simulated the overall aroma profile of SP. The changes in odorants during storage were investigated further. With increasing concentrations and OAVs during storage, hexanal became an off-flavor compound.


[Transplacental infection by lymphocytic choriomeningitis virus. Results of a retrospective serological study in France (author's transl)].
A study was made on the presence of antibodies against lymphocytic choriomeningitis virus in 452 children in the Lyon area who had suffered from either a major pathological condition or a congenital malformation at birth. Of 34 cases of congenital hydrocephalus, only one could be definitely attributed to a maternal infection with the virus, occurring between the 5th and 6th months of pregnancy. Lymphocytic choriomeningitis virus should thus be added to the list of those which are potentially teratogenic for the human species.


[Case studies of bacterial species responsible for urinary tract infections and their sensitivity to antibiotic treatment].
A microbiological assessment was made of 829 urine specimens to determine the percentage incidence of different bacterial species and their susceptibility to antibiotic treatment. It was found that E. coli was most common, followed by Pseudomonas, Proteus, Staphylococcus, Candida, faecal Streptococcus, and Shigella. The results suggest that the aetiological agent should be systematically ascertained and an antibiogram run before a treatment programme is laid down.


Ecological niche modeling of rabies in the changing Arctic of Alaska.
Rabies is a disease of global significance including in the circumpolar Arctic. In Alaska enzootic rabies persist in northern and western coastal areas. Only sporadic cases have occurred in areas outside of the regions considered enzootic for the virus, such as the interior of the state and urbanized regions. Here we examine the distribution of diagnosed rabies cases in Alaska, explicit in space and time. We use a geographic information system (GIS), 20 environmental data layers and provide a quantitative non-parsimonious estimate of the predicted ecological niche, based on data mining, machine learning and open access data. We identify ecological correlates and possible drivers that determine the ecological niche of rabies virus in Alaska. More specifically, our models show that rabies cases are closely associated with human infrastructure, and reveal an ecological niche in remote northern wilderness areas. Furthermore a model utilizing climate modeling suggests a reduction of the current ecological niche for detection of rabies virus in Alaska, a state that is disproportionately affected by a changing climate. Our results may help to better inform public health decisions in the future and guide further studies on individual drivers of rabies distribution in the Arctic.


Cervical spine stabilization in pediatric patients: evaluation of current techniques.
We evaluated the performance of commercially available infant and pediatric cervical collars, both alone and in combination with commonly used supplemental devices (eg, Kendrick Extrication Device, half-spine board). One infant and 11 pediatric-sized collars were tested on mannequins representing an infant and a 5-year old child. Maximum forces generated by cooperative children were measured, then applied to the mannequins to reproduce head and neck flexion, extension, rotation, and lateral motion. Limitation of motion was measured in each direction for each collar and combination method. In general, collars of rigid plastic construction performed better than did foam types. However, when used alone none of the collars provided acceptable immobilization, with even the best allowing 17 degrees flexion, 19 degrees extension, 4 degrees rotation, and 6 degrees lateral motion. When combined with supplemental devices, immobilization to 3 degrees or less in any direction could be achieved. Findings were verified using cooperative children and selected collars. Overall, combination methods were more effective than cervical collars alone (P less than .001) or supplemental devices alone (P less than .05). The modified half-spine board used with a rigid collar and tape was the most effective combination method. We conclude that prehospital cervical spine stabilization in pediatric patients is best accomplished using a rigid-type cervical collar in combination with supplemental devices as described.


Mass Spectrometric Analysis of Mitochondrial RNA Modifications.
Mitochondrial RNAs are modified posttranscriptionally. These modifications are required for proper functioning of RNA molecules, and thereby contribute to essential mitochondrial processes. Herein, we describe our latest mass spectrometry-based platform for analysis of posttranscriptional modifications of mitochondrial tRNAs, and measuring the in vitro activity of mitochondrial RNA-modifying enzymes.


Protease activity in cells of Bacillus megaterium during derepression.
A proteolytic activity hydrolyzing denatured proteins of Bacillus megaterium labelled with 35S or 14C amino acids was detected in cells of the asporogenic strain of Bacillus megaterium. The substrate is hydrolyzed by the enzyme or enzymes at optimum pH around 7, their activity being almost completely inhibited by EDTA and o-phenanthroline. PMSF, the inhibitor of serine proteases, is slightly inhibitory. Gel filtration on a Sephadex column separated the protease activity to two or three fractions. The protease activity in cells with the repressed synthesis of protease corresponds to 5-20 mug of substrate degraded per hour by 1 mg of protein at 37 degrees C. It increases five to ten-fold during the derepression. When the intracellular protease activity increases the extracellular enzyme begins to be excreted into the medium. The intracellular protease activity rapidly decreases after the addition of chloramphenicol or of a mixture of amino acids to the derepressed culture. Half or even more of the protease activity is released from the cells during their conversion to protoplasts by means of lysozyme. This "periplasmic" activity remains mostly in the supernatant also after mesosomes have been centrifuged down from the periplasm. A portion of the activity bound in protoplasts sediments together with membrane fraction after their lysis.


Thermostabilization of indigenous multiplex polymerase chain reaction reagents for detection of enterotoxigenic Staphylococcus aureus.
Among DNA-based techniques, polymerase chain reaction (PCR) is the most widely accepted molecular tool for the detection of pathogens. However, the technique involves several reagents and multiple pipetting steps that often lead to error-prone results. Additionally, the reagents entail a cold-chain facility to maintain their stability during storage and transportation. The main aim of the present study was to simplify the utility of a pre-optimized multiplex PCR format that was developed to detect toxigenic strains of Staphylococcus aureus by providing stable, pre-mixed, and ready-to-use master mix in a lyophilized formulation. Master mix containing all reagents except the template was lyophilized in the presence of an excipient lyoprotectant to achieve long-term stability without altering the sensitivity, specificity and PCR performance. Bromophenol blue was also included in the master mix to reduce the risk of external contamination during gel loading. The stability of lyophilized master mix was analyzed at different temperatures. The PCR performance was also examined after exposure of master mix to notable temperature fluctuations during transportation. The shelf-life of lyophilized master mix was estimated to be 1.5 months at ambient temperature and 6 months at 4°C. Stability was unaffected by temperature fluctuations during transportation even in cold-chain-free conditions, thus reducing the cost required for cold storage. The sensitive, cost-effective, ready-to-use, and ambient temperature stable formulation could be implemented as a detection tool in food analysis and diagnostic laboratories and hospitals and for on-field application outside the laboratories, as well as for detection of toxigenic strains of S. aureus.


Phenotypic characteristics of lymphocyte populations isolated from middle gestation human placenta.
In order to characterize the phenotypic composition of populations of lymphoid cells in maternal and fetal tissues during the period of middle gestation, mononuclear cells were isolated from maternal peripheral blood, fetal spleen, fetal thymus and placenta of 18-24 week pregnancies. Peripheral blood and placental isolates were stained for a number of lymphoid cell markers by indirect immunofluorescence and analyzed by flow cytometry. Studies were performed on both freshly isolated mononuclear cell preparations and in vitro cultured cells after selective expansion in interleukin 2 (IL2). Fresh placental mononuclear cell isolates were an average 20% CD3+; their CD4/CD8 ratios varied among individuals. An average of 68% of the lymphocytes isolated from maternal peripheral blood were CD3+. Placental and maternal peripheral blood isolates had comparable percentages of CD16+ and CD20+ cells, while CD56+ cells were present at significantly greater numbers in the lymphocyte compartment of placenta (17%) than in peripheral blood (3%; P < 0.01). Lymphocyte isolates were expanded by culture with IL2 and PHA and stained to determine if propagated lymphocyte populations are representative of initial isolates. Expansion of all lymphocyte isolates favored CD3 phenotypes and CD8 phenotypes. Compared to expanded placenta-derived populations, expanded peripheral blood lymphocytes were similar with regard to percentages of all phenotypes except gamma/delta T cells which represented more of placental lymphocytes (10%) than peripheral lymphocytes (5%; P < 0.01). Surface HLA typing determined propagated placenta-derived lymphocytes to be of maternal and not fetal origin. In vitro propagation of placental mononuclear cell isolates may therefore provide populations of maternal CD3+ lymphocytes for assessment of function and specificity.


Effect of dietary supplement on nutritional status and clinical outcome in 501 geriatric patients--a randomised study.
The present study was designed to evaluate to the effect of dietary supplements on clinical outcome and nutritional status in a large group of geriatric patients (n = 501). The patients were randomised into an experimental group which received nutritional supplementation (400 kcal) as well as a standard hospital diet, and a control group on hospital diet alone. The nutritional state was measured on admission and after 8 and 26 weeks by anthropometry, serum protein analysis and a delayed hypersensitivity skin test. Protein energy malnutrition was defined as the presence of three or more abnormal parameters. 28.5% of patients showed evidence of malnutrition on admission. Hospitalisation itself resulted in a gradual deterioration in nutritional status. Nutritional supplementation generally improved nutritional state. Among those patients who were well nourished on admission, and subsequently receiving dietary supplementation, 8.3% fulfilled malnutrition criteria after 26 weeks, while 21.1% were considered malnourished in the control group (p < 0.05). The improvement observed in transport proteins was probably related to nutritional support and not just to the reversal of inflammation. In the initially well nourished group of more than 300 patients, the mortality rate was 8.6% in those given nutritional support compared to 18.6% in the control group (p < 0.02).


Pancreatic secretory response to ordinary meals: studies with pure pancreatic juice.
We have studied the pancreatic secretory response to a normal meal in 5 subjects with an external drainage of the main pancreatic duct carried out after biliary tract surgery. Pancreatic juice was collected at 60-min intervals from 10 AM to 7 PM, starting 2 h before and ending 7 h after lunch, and was analyzed for volume, bicarbonate content, and protein content. Large doses of pancreatic extract were given between and during meals. Both bicarbonate and protein output increased rapidly after the beginning of the meal and the increase persisted, with minor fluctuations, for the entire 7-h study period between lunch and dinner. The peak postprandial bicarbonate and protein outputs were higher (on average by 20% and 26%, respectively) than bicarbonate and protein outputs induced by exogenous infusion of submaximal doses of secretin and cerulein. The profile and magnitude of the bicarbonate secretory pattern elicited by food were not substantially different from those of protein secretion. In an additional patient who had undergone a duodenocephalopancreatectomy plus two-thirds distal gastrectomy before the study, the pancreatic response to meals showed an initial phase characterized by an increase in pancreatic secretion during the first postprandial hour followed by a tendency to decrease in the subsequent 2 h, and a later phase (from the fourth postprandial hour to the end of the study) characterized by a more marked and more persistent increase in pancreatic secretion than occurred in the initial 3 h. These data indicate that (a) the pancreatic secretory response to ordinary meals is much more prolonged than is generally believed. The late phase of the response is not dependent on gastric emptying of food into the duodenum, but is probably related to the arrival of chyme in the distal ileum. (b) The pancreatic secretory response to a normal meal is quantitatively slightly higher than that produced by exogenous pancreatic stimulation with submaximal doses of secretin and cerulein. (c) The pattern of postprandial bicarbonate secretion is similar to that for protein.


Effect on 30-Day Readmissions after Early Versus Delayed Discharge after Uncomplicated Transcatheter Aortic Valve Implantation (from the Nationwide Readmissions Database).
Early discharge after transcatheter aortic valve implantation has been shown to be safe in single-center studies and trials, but outcomes in broader clinical practice are unknown. Using the National Readmission Databases (1/2014 to 9/2015), we compared 30-day readmission rates between early (<3 days) and late (≥3 days) discharges after uncomplicated endovascular TAVR in a propensity-matched cohort. We examined factors associated with failure of early discharge by testing for interactions of patient factors with discharge strategy. Among 4,955 hospitalizations for uncomplicated TAVR, 1,857 (37%) were discharged early with substantial site-level variability (range 0% to 87%; median odds ratio 3.69). In the propensity matched cohort (n = 3,346), there were similar rates of 30-day readmission by discharge strategy (early vs late: 10.3% vs 10.6%; stratified log-rank p = 0.555). There was a statistically significant interaction between discharge strategy and number of chronic conditions (p = 0.007), where readmission rates were lower in patients discharged early in those with 0 to 4 chronic conditions, but not in those with 5 to 10 or >10. In conclusion, in a large "real-world" cohort, early discharge after uncomplicated TAVR was not associated with a higher rate of 30-day rehospitalization, yet there was significant variability across US hospitals. No patient characteristics were associated with increased risk of readmission with early discharge.


Association between alanine aminotransferase within the normal range and all-cause and cause-specific mortality: A nationwide cohort study.
We sought to determine the association between alanine aminotransferase (ALT) in the normal range and mortality in the absence of liver dysfunction to better understand ALT's clinical significance beyond liver injury and inflammation. A cohort of 2,708 male and 3,461 female adults aged 20-75 years without liver dysfunction (ALT<30 in males & <19 in females, negative viral serologies, negative ultrasound-based steatosis, no excess alcohol consumption) from the National Health and Nutrition Examination Survey (NHANES)-III (1988-1994) were linked to the National Death Index through December 31, 2015. Serum ALT levels were categorized into sex-specific quartiles (Females: <9, 9-11, 11-14, ≥14 IU/L, Male: <12, 12-15, 15-20, ≥20 U/L). The primary outcome was all-cause mortality. Hazard ratios (HRs) were estimated, adjusting for covariates and accounting for the complex survey design. Relative to males in the lowest quartile (Q1), males in the highest quartile (Q4) had 44% decreased risk of all-cause mortality (aHR [95% CI]: 0.56 [0.42, 0.74]). Females in Q4 had 45% decreased risk of all-cause mortality (aHR [95% CI]: 0.55 [0.40, 0.77]). Males with BMI <25 kg/m2 in Q4 had significantly lower risk of all-cause mortality than Q1; however, this association did not exist in males with BMI ≥25 (BMI<25: 0.36 [0.20, 0.64], BMI≥25: 0.77 [0.49, 1.22]). Risk of all-cause mortality was lower in males ≥50 years than in males<50 (age≥50: 0.55 [0.39, 0.77], age<50: 0.81 [0.39, 1.69]). These age- and BMI-related differences were not seen in females. ALT within the normal range was inversely associated with all-cause mortality in U.S. adults.


Late occurrence of perineal wound abscess years after total colectomy.
Seven patients presented with a large perineal abscess eight months to seven years after complete healing of the perineal wound following proctocolectomy. Six patients had had total proctocolectomies for ulcerative colitis and a seventh had undergone abdominoperineal resection for cancer. A typical clinical picture of perineal pain, fever, urinary tract complaints (including retention), and minimal local perineal findings was present. Prostatitis or a urinary tract infection was considered in five patients, but none of them responded to antibiotics. Ultrasound examination of the perineum may confirm the diagnosis; however, diagnostic and therapeutic surgical exploration of the healed perineum is recommended when this diagnosis is unclear.


A case of adrenal infarction in a patient with COVID 19 infection.
This case report highlights an unusual presentation of acute adrenal infarction in a Covid-19 patient who presented with abdominal symptoms and hyponatraemia. We discuss the recent literature reviewing how Covid-19 creates a hypercoaguable state, with acute adrenal infarction as a possible prothrombotic complication.


Development of a subdural vein thrombosis following aggressive factor VII replacement for postnatal intracranial haemorrhage in a homozygous factor VII-deficient infant.
Congenital factor VII deficiency is a rare (1:500,000) autosomally recessive coagulopathy with variable expression and high penetration. In infants the most devastating presentation is that of intracranial haemorrhage. An infant is described with severe factor VII deficiency who developed postnatal intracranial haemorrhage. The baby was treated with factor VII concentrate (ImmunoA.G., Vienna, Austria). Three weeks after the haemorrhage he developed a dural venous sinus thrombosis. Although factor VII-deficient patients may need treatment with factor VII concentrate, this needs to be carefully monitored because of the thrombotic risk.


Eosinophilic polymyositis presenting as a pseudotumour in the hypereosinophilic syndrome.
This report describes an unusual case of pseudotumour of muscle caused by an eosinophilic myositis associated with peripheral blood eosinophilia, systemic illness and a pericardial effusion. The relationship of this case to other reported cases of eosinophilic myositis and the hypereosinophilic syndrome is discussed briefly.


Effects of prenatal exposure to (es)citalopram and maternal depression during pregnancy on DNA methylation and child neurodevelopment.
Studies assessing associations between prenatal exposure to antidepressants, maternal depression, and offspring DNA methylation (DNAm) have been inconsistent. Here, we investigated whether prenatal exposure to citalopram or escitalopram ((es)citalopram) and maternal depression is associated with differences in DNAm. Then, we examined if there is an interaction effect of (es)citalopram exposure and DNAm on offspring neurodevelopmental outcomes. Finally, we investigated whether DNAm at birth correlates with neurodevelopmental trajectories in childhood. We analyzed DNAm in cord blood from the Norwegian Mother, Father and Child Cohort Study (MoBa) biobank. MoBa contains questionnaire data on maternal (es)citalopram use and depression during pregnancy and information about child neurodevelopmental outcomes assessed by internationally recognized psychometric tests. In addition, we retrieved ADHD diagnoses from the Norwegian Patient Registry and information on pregnancies from the Medical Birth Registry of Norway. In total, 958 newborn cord blood samples were divided into three groups: (1) prenatal (es)citalopram exposed (n = 306), (2) prenatal maternal depression exposed (n = 308), and (3) propensity score-selected controls (n = 344). Among children exposed to (es)citalopram, there were more ADHD diagnoses and symptoms and delayed communication and psychomotor development. We did not identify differential DNAm associated with (es)citalopram or depression, nor any interaction effects on neurodevelopmental outcomes throughout childhood. Trajectory modeling identified subgroups of children following similar developmental patterns. Some of these subgroups were enriched for children exposed to maternal depression, and some subgroups were associated with differences in DNAm at birth. Interestingly, several of the differentially methylated genes are involved in neuronal processes and development. These results suggest DNAm as a potential predictive molecular marker of later abnormal neurodevelopmental outcomes, but we cannot conclude whether DNAm links prenatal (es)citalopram exposure or maternal depression with child neurodevelopmental outcomes.


[Surgical treatment of combined vertical tropias: dissociated vertical deviation and primary hyperfunction of the inferior oblique ocular muscles].
We have treated 27 children with DVD and primary overaction of the inferior oblique muscles in the same time. In all of them we have done recession of the inferior oblique muscles (for 4, 6, 8 or 10 mm). In only seven of them we did recession of the superior recti (for 7, 8 or 9 mm) simultaneously. DVD doesn't need to be operated in every child. Large recession of the superior rectus muscles very significantly and adequately ameliorate the DVD in 79% of children. Hypocorrection of the DVD we have in another 21% of the operated eyes. We get valid results one month after the surgery. They were constant after six months too.


Labeling fibroblasts with biotin-BSA-GdDTPA-FAM for tracking of tumor-associated stroma by fluorescence and MR imaging.
Fibroblasts at the tumor-host interface can differentiate into myofibroblasts and pericytes, and contribute to the guidance and stabilization of endothelial sprouts. After intravenous administration of biotin-BSA-GdDTPA-FAM in mice with subcutaneous MLS human ovarian carcinoma tumors, the distribution of the macromolecular MRI/optical contrast material was confined to blood vessels in normal tissues, while it co-registered with alphaSMA-positive stroma tracks within the tumor. These alphaSMA-positive tumor-associated myofibroblasts and pericytes showed uptake of the contrast material into intracellular granules. We evaluated the use of this contrast material for in vitro labeling of tumor fibroblasts as an approach for tracking their involvement in angiogenesis. Fluorescence microscopy demonstrated internalization of the contrast material, and MRI revealed a significant increase in the R(1) relaxation rate of labeled fibroblasts. R(1) not only remained elevated for 2 weeks in culture, it also increased with cell proliferation, indicating prolonged retention of the contrast material and subsequent intracellular processing and redistribution of the material, and thereby enhancing MR contrast. Moreover, cells that were labeled ex vivo with MR contrast material and co-inoculated with tumor cells in mice were detected in vivo by MRI. Uptake of the contrast material was suppressed by nystatin, suggesting internalization by caveolae-mediated endocytosis. This study shows that labeling of fibroblasts with biotin-BSA-GdDTPA-FAM is feasible and would allow noninvasive in vivo tracking of fibroblasts during tumor angiogenesis and vessel maturation.


Thromboxane molecules do not adopt the prostaglandin hairpin conformation.
The hairpin conformational hypothesis has been proposed to rationalise much of the structure-activity and receptor-binding data which have accumulated for the prostaglandin (PG) hormones. The hairpin conformation, thought to be necessary for PG activity, requires that the alpha- and omega-chains of the molecule be extended and in parallel alignment, separated by a van der Waals contact distance for the full length of the chains, with the ends of the chains approximately 5.5 A apart. The similarity between the structures of the thromboxanes (TXs) and the PGs suggests that the profile of activity of TXs, like that of PGs, centres on subtle conformational variation of the hairpin geometry. Thromboxane B2 (TXB2) is a stable hydrolysis product of a highly reactive, short-lived intermediate, thromboxane A2 (TXA2), which is formed from the prostaglandin endoperoxide (PGH2) as indicated in Fig. 1. An examination of molecular models of TXA2 and TXB2 suggests that the structural differences between the ring moieties may have much less influence in altering the side-chain conformation of TXs than do substitutents on the relatively more flexible cyclopentane ring of a PG molecule. We report here the first diffraction analysis of a thromboxane structure and note that the molecular conformation is not hairpin shaped.