Molecular identification of food-borne and water-borne protozoa.
Cryptosporidium and Giardia can be transmitted to humans by contaminated food and water, resulting in large outbreaks of diarrheal disease. Sensitive methods for detecting these parasites are needed to control and prevent infection. However, this issue is complicated by the fact that there is still uncertainty about the role played by different species/genotypes with respect to human disease. We are in the process of collecting samples from clinical cases (both sporadic and outbreak-related human infections) and from the environment (tap and waste water samples from different geographic regions), to test the efficacy of methods for detection and genotyping. Concerning Cryptosporidium parvum, we have developed new genotyping methods based on highly polymorphic microsatellite markers. The use of microsatellite markers allows the route of transmission to be traced; these methods can also be used not only to distinguish between anthroponotic and zoonotic transmission but also to identify the source(s) of infection. Regarding Giardia, which was found very frequently in environmental water samples, we are testing the beta-giardin gene as a marker to discriminate among species/genotypes.


Flaw-Containing Alumina Hollow Nanostructures Have Ultrahigh Fracture Strength To Be Incorporated into High-Efficiency GaN Light-Emitting Diodes.
In the present study, we found that α-alumina hollow nanoshell structure can exhibit an ultrahigh fracture strength even though it contains a significant number of nanopores. By systematically performing in situ mechanical testing and finite element simulations, we could measure that the fracture strength of an α-alumina hollow nanoshell structure is about four times higher than that of the conventional bulk size α-alumina. The high fracture strength of the α-alumina hollow nanoshell structure can be explained in terms of conventional fracture mechanics, in that the position and size of the nanopores are the most critical factors determining the fracture strength, even at the nanoscales. More importantly, by deriving a fundamental understanding, we would be able to provide guidelines for the design of reliable ceramic nanostructures for advanced GaN light-emitting diodes (LEDs). To that end, we demonstrated how our ultrastrong α-alumina hollow nanoshell structures could be successfully incorporated into GaN LEDs, thereby greatly improving the luminous efficiency and output power of the LEDs by 2.2 times higher than that of conventional GaN LEDs.


Increased cardiorespiratory coordination in preeclampsia.
Preeclampsia is one of the main sources of morbidity in pregnancy with a high mortality rate without a known ultimate cause. Using a corpus including 927 measurements of pregnant women with and without different hypertonic diseases at multiple stages of pregnancy, we utilised a new approach to analyse cardiorespiratory coordination. Since the recording quality of respiratory effort was limited due to a high signal to noise ratio, we applied an ECG derived respiration approach to create an ersatz respiratory signal. After applying the few available recordings with a sufficiently high quality of the respiratory signal to validate the substitute, coordigrams were calculated and quantified by utilising an epsilon method. We showed significant (p < 0.05) differences in the coordination in a matched (BMI, age, gestational week) comparison of preeclamptic and healthy subjects. Hopefully future applications of and improvements on these methods are able to create a fast and convenient prediction methodology to reduce the impact of this disease as well as help in the determination of its underlying cause.


Influence of aging on the carcinogen-induced protein kinase activity in rat liver cell nuclei.
A carcinogen-induced increase in a protein kinase activity was found in cell nuclei of rat liver. The enzyme was extracted from isolated nuclei with a hypotonic buffer, retained to an anion-exchange column, eluted with 0.15 M NaCl containing solution and to be measured for the activity with casein as the substrate, showing a nature of a casein kinase. The change in the activity during the course of aging was studied with 5-, 10-, and 50-week old Wistar male rats. The activity was highest in 5-week-old rat but decreased in 10- and 50-week-old animal. A hepatocarcinogen, thioacetamide, induced an increase in activity in 10-week old rats but rather decreased in 5- and 50-week-old rats. Aging suppresses the activity of this unique enzyme. Thioacetamide abolishes this suppression resulting in an increase in the activity of the enzyme at a certain stage of aging.


Dynamics of a delay turbidostat system with contois growth rate.
In this contribution, the dynamic behaviors of a turbidostat model with Contois growth rate and delay are investigated. The qualitative properties of the system are carried out including the stability of the equilibria and the bifurcations. More concretely, we exhibit the transcritical bifurcation by reducing the system without delay to a 1-dimensional system on a center manifold and find that Hopf bifurcation occurs by choosing the delay as bifurcation parameter. Also, using the normal form theory and the center manifold theorem we determine the direction and stability of the bifurcating periodic solutions induced by the Hopf bifurcation. Finally, numerical simulations are presented to support our theoretical results.


Evaluating the effects of common control measures for influenza A (H1N1) outbreak at school in China: A modeling study.
Influenza A (H1N1) outbreaks have become common at schools in China since 2009. However, the effects of common countermeasures for school influenza outbreak have not been quantified so far, including isolation, vaccination, antivirus and school closure. We conducted a mathematically modeling study to address this unsolved issue. We collected data of all small-scale school outbreaks caused by influenza A that occurred in Changsha city between January 2009 and December 2013. Two outbreaks (one was in 2009 and the other one was in 2013) were used for simulating the effects of single and combined use of common measures, including isolation (Iso), therapeutics (T), prophylactics (P), vaccinating 70% of susceptible individuals prior to the outbreak (VP70), vaccinating 70% of susceptible individuals every day during the outbreak (VD70) and school closure of one week (S1w). A susceptible-exposed-infectious/asymptomatic-recovered (SEIR) model was developed to implement the simulations based on the natural history of influenza A. When no control measures are taken, the influenza is expected to spread quickly at school for the selected outbreak in 2013; the outbreak would last 56 days, and the total attack rate (TAR) would reach up to 46.32% (95% CI: 46.12-46.52). Of all single control measures, VP70 is most effective to control the epidemic (TAR = 8.68%), followed by VP50, VD70, VD50 and Iso. The use of VP70 with any other measure can reduce TAR to 3.37-14.04% and showed better effects than any other combination of two kinds of measures. The best two-measure combination is 'S1w+VP70' (TAR = 3.37%, DO = 41 days). All combinations of three kinds of measures were not satisfactory when Vp70 and VD70 were excluded. The most effective three-intervention combination was 'Iso+S1w+VP70' (with TAR = 3.23%). When VP70 or VD70 is included, the combinations of four or five kinds of interventions are very effective, reducing TAR to lower than 5%. But the TAR of combination of 'T+P+Iso+S1w' is 23.20%. Similar simulation results were observed for the selected outbreak in 2009. Vaccinating no less than 70% of individuals prior to the outbreak and isolation are recommended as single measures to control H1N1outbreak at school. The combination of VP70+S1w can achieve very good control for school outbreak.


Quantitative analysis of the relationship between intra- axonal neurofilament compaction and impaired axonal transport following diffuse traumatic brain injury.
Traumatic axonal injury (TAI) following traumatic brain injury (TBI) contributes to morbidity and mortality. TAI involves intra-axonal changes assumed to progress to impaired axonal transport (IAT), disconnection, and axonal bulb formation. Immunocytochemical studies employing antibodies to amyloid precursor protein (APP), a marker of IAT and RMO14, a marker of neurofilament compaction (NFC), have shown that TAI involves both NFC and IAT, with the suggestion that NFC leads to IAT. Recently, new data has suggested that NFC may occur independently of IAT. The objective of this study was to determine quantitatively the precise relationship between NFC and IAT. Following TBI, rats were studied at 30 min, 3 h, and 24 h. Using single-label immunocytochemistry employing the antibodies RM014, APP, or a combined labeling strategy targeting APP/RMO14 in aggregate, the immunoreactive (IR) profiles were counted in the corticospinal tract (CSpT) and medial lemniscus (ML). In the CSpT, the number of axons demonstrating RMO14-IR approximated the number of axons showing APP-IR, with the APP-IR population showing a significant increase over 24 h (p < 0.05). The sum of both single-label counts equaled the aggregate APP/RMO14 numbers, demonstrating little relationship between NFC and IAT. In the ML, 75% of fibers demonstrated a separation of APP-IR and NFC-IR; however, 25% of the ML fibers showed co-localization of APP-IR and RMO14. The results of these studies indicate that, in the majority of damaged axons, NFC is not associated with IAT. Our findings argue for the use of multiple markers when evaluating the extent of TAI or the efficacy of therapies targeting the treatment of TAI.


Neurotransmitters regulating vestibular commissural inhibition in the cat.
The present study focuses on the transmitters which control the vestibular neural activity and, in particular, those which regulate commissural inhibition. Extracellular spike recordings were taken from single vestibular neurons of decerebrate cats. Seven-barreled electrodes were used. The barrels, except for the central one, were filled with several transmitter candidates and their specific inhibitors. After isolation of a type I neuron, the chemicals were iontophoretically applied to examine their effects on the activity of the neuron. The results were as follows: i) GABA and glycine markedly decreased spontaneous firing of the neurons, while serotonin did not change the activity. ii) Bicuculline abolished the inhibitory effects of GABA on the neurons. iii) Strychnine also abolished the effects of glycine, iv) Commissural inhibition caused by electrical stimulation of the contralateral labyrinth was not abolished by the application of strychnine but was abolished by bicuculline. We concluded that 1) vestibular type 1 neurons are controlled by GABAergic and glycinergic neurons, and that 2) the commissural inhibition is activated by the GABAA receptor, but not by the GABAB receptor.


Tranexamic Acid in Total Hip Arthoplasty: Management of Complications and Use.
Use of tranexamic acid for management of blood loss in total hip arthroplasty is growing. It is important for healthcare providers to be aware of the pharmacology, efficacy, management, complica- tions, and side effects of this medication.


A study of maximal oxygen consumption in Chinese males.
Maximal oxygen intake has been proposed as a standard for cardiovascular fitness. Measurement of maximal heart rate, blood pressure, oxygen consumption, and exercise duration can assess the individuals' functional aerobic capacity or reserve resulting from cardiac disease. The purpose of the present study is to evaluate the physiologic response to maximal treadmill exercise. The Chinese Air Force protocol (CAF protocol - a constant speed of 5.6 kmph with a 5% increase in grade every 3 min) was used in 202 healthy men of 30 to 57 years of age. Their mean maximal heart rate and maximal oxygen consumption are 181 b.m-1 and 40.4 ml.kg-1.m-1, respectively. The study revealed that aging bears a prominent influence on maximal heart rate and maximal diastolic pressure but not on systolic pressure. There are two major influences on max .Vo2, namely, age and habitual physical activity level. Activity had a more significant effect than the age factor. Maximal oxygen consumption was lower in sedentary than in physically active persons and diminished with age. It had a high correlation with duration of exercise by this standardized protocol. Accordingly by regression equations, average normal values from healthy persons could be predicted from activity status and age, and values expected on testing could be estimated from the duration of the exercise.


How Does the Optimism of Students Learning a Foreign Language Affect Their Creative Self-Efficacy? The Mediating Effects of Hope and Empathy.
Creative self-efficacy (CSE) is a core influencer of creative behavior and has a positive impact on well-being and development. However, the positive psychological processes that help to promote CSE in foreign-language learning (FLL) remain under-studied. Focusing specifically on FLL students, the present study examined the associations among optimism, hope, empathy, and CSE and investigated the possible mediating roles of hope and empathy in the relationship between optimism and CSE. A sample of 330 FLL students from two Chinese universities participated in this study. The results showed that (i) optimism, hope, and empathy were all positively related to CSE and that (ii) optimism did not directly predict CSE but indirectly and positively predicted CSE through hope and empathy. These findings suggest that optimism, empathy, and hope potentially play positive roles in facilitating CSE in FLL students. Based on the present results, some practical approaches are discussed that could help improve the CSE of FLL students, paying particular attention to the effects that potentially motivate their positivity.


The Prospective Prognostic Value of Biopsychosocial Indices of Sensitivity to Physical Activity Among People With Back Pain.
Many people living with musculoskeletal pain conditions experience a range of negative biopsychosocial responses to physical activity, referred to as increased sensitivity to physical activity (SPA), that may undermine successful rehabilitation. This exploratory study aims to provide the first prospective analysis of the potential prognostic value of 3 biopsychosocial indices of SPA in relation to rehabilitation outcomes. This study also aimed to shed light on the cross-sectional interrelationships between these 3 biopsychosocial indices of SPA. Adults with back pain were evaluated upon starting physical therapy and then again 3 months later. The initial testing session consisted of self-reported pain-related questionnaires and assessment of activity-related changes in pressure pain thresholds (SPA-Sensory), pain intensity ratings (SPA-Pain), and situational catastrophizing (SPA-Psych). The 3-month follow-up consisted of self-reported disability and pain questionnaires. Correlational and hierarchical linear regression analyses were conducted. A total of 97 participants completed both the initial visit and 3-month follow-up. The SPA-Pain index and the SPA-Psych index were significantly intercorrelated, but neither were correlated with the SPA-Sensory index. The SPA-Sensory index was not correlated with outcomes. The SPA-Pain index was correlated only with cross-sectional disability and pain outcomes. The SPA-Psych index was the only SPA index significantly correlated with outcomes both cross-sectionally and at 3-month follow-up. After controlling for baseline pain/disability and pain catastrophizing, SPA-Psych was no longer a significant prognostic factor for pain, but remained a significant prognostic factor for disability at 3-month follow-up (β=0.272, t=2.674, P=0.008, R2 Δ=5.60%). This study highlights the importance of conceptualizing and measuring SPA as a biopsychosocial (rather than unidimensional) construct and points toward the added prognostic value of this construct. Implications for future research and practice are discussed.


Hypermobility in women with fibromyalgia syndrome.
The purpose of this study was to evaluate the relationship between hypermobility and fibromyalgia syndrome (FS) in women. Ninety-three women with FS who met the American College of Rheumatology criteria for FS and 58 healthy women without FS were included in this study. All women were examined for hypermobility by blinded observers using the Beighton criteria. The mean age was 43.5+/-9.9 (21-68) and 40.2+/-11.1 (21-63) years in the FS and control groups, respectively, and the two groups were statistically similar (p>0.05). The mean Beighton total score was 4.7+/-2.1 and 2.9+/-2.4 in the FS and control groups, respectively (p<0.0001). The frequency of joint hypermobility was 64.2% in the FS group and 22% in the control group. In accordance with the Beighton criteria (p<0.05), we found that the joint hypermobility ratio was significantly higher in patients with FS than in subjects without FS. Additionally, we evaluated the correlation between the total Beighton score and the age and number of trigger points. There were negative correlations between the total Beighton score and the age (r=-0.42, p<0.001) and number of trigger points (r=-0.24, p=0.03) in all patients. Hypermobility syndrome is more common in women with FS than in those in the control group. Therefore, the relationship between hypermobility and FS should be taken into consideration in the diagnosis and follow-up of women, especially those with widespread pain.


Rosa laevigata Michx. Polysaccharide Ameliorates Diabetic Nephropathy in Mice through Inhibiting Ferroptosis and PI3K/AKT Pathway-Mediated Apoptosis and Modulating Tryptophan Metabolism.
Diabetic nephropathy (DN) is a metabolic disease wherein chronic hyperglycemia triggers various renal cell dysfunctions, eventually leading to progressive kidney failure. Rosa laevigata Michx. is a traditional Chinese herbal medicine. Many studies have confirmed its antioxidative, anti-inflammatory, and renoprotective effects. However, the effects and mechanisms of Rosa laevigata Michx. polysaccharide (RLP) in DN remain unclear. In this study, a DN mouse model was established to investigate the therapeutic effect of RLP on DN mice. Then, nontargeted metabolomics was used to analyze the potential mechanism of RLP in the treatment of DN. Finally, the effects of RLP on ferroptosis and the PI3K/AKT pathway were investigated. The results demonstrated that RLP effectively alleviated renal injury and reduced inflammation and oxidative stress in the kidney. In addition, nontargeted metabolomic analysis indicated that RLP could modulate riboflavin metabolism and tryptophan metabolism in DN mice. Notably, ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney were also ameliorated following RLP treatment. In conclusion, this study confirmed that RLP had a significant therapeutic effect on DN mice. Furthermore, RLP treatment modulated tryptophan metabolism and inhibited ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney.


Peptide ladder sequencing by mass spectrometry using a novel, volatile degradation reagent.
A conceptually novel approach to protein sequencing involves the generation of ragged-end polypeptide chains followed by mass spectroscopic analysis of the resulting nested set of fragments. We report here on the synthesis and development of a volatile isothiocyanate (trifluoroethylisothiocyanate) that allows the identification of several consecutive residues starting with a few picomoles of peptide. The nested set of peptides is generated simply by adding equal aliquots of starting peptide each cycle and driving both the coupling and cleavage reactions to completion. No additional reagents are required to act as chain terminators and retention of the peptide terminal amine allows for subsequent modification with quaternary ammonium alkyl NHS esters to improve sensitivity. Complex washing procedures are not required each cycle, as reagents and by-products are efficiently removed under vacuum, eliminating extractive loss. Multiple peptide samples can be processed simultaneously, with each degradation cycle completed in 35-40 min. The inherent simplicity of the process should allow for easy automation and permit rapid processing of samples in parallel.


Human genetic susceptibility to Candida infections.
Infections with Candida spp. have different manifestations in humans, ranging from mucosal to bloodstream and deep-seated disseminated infections. Immunocompromised patients have increased susceptibility to these types of infections, due to reduced capacity to elicit effective innate or adaptive immunity. In addition, rare and common genetic variants in the human genome have been identified that influence susceptibility to Candida infections. Genetic determinants of primary immunodeficiencies leading to chronic mucocutaneous candidiasis have been reported, and polymorphisms in genes that are known to be involved in anti-Candida host defense are associated with increased susceptibility to systemic infection. These findings have greatly increased our understanding of pathways important for anti-Candida defense in humans, and patterns of prevalence of Candida infections. In addition, these pathways may offer novel therapeutic targets for treatment. This review provides an overview of the current insights in genetic susceptibility to Candida infections and their consequences for the immune response against Candida.


Tumor Differentiation as a Prognostic Marker in Clinically Staged T1bN0 Esophageal Adenocarcinoma.
Current guidelines recommend that clinically staged T1N0 esophageal cancers are to be referred to surgery or endoscopic resection. Using the National Cancer Database, we identified 733 individuals with clinically staged T1N0 esophageal carcinoma, who underwent upfront surgery and did not receive any prior treatment. We assessed upstaging, which was defined as ≥ T2 disease or positive lymph nodes. Poorly differentiated adenocarcinomas were associated with upstaging, whereas squamous cell carcinomas were not. Specifically, the percentage of upstaging among individuals with clinically staged T1b and poorly differentiated tumor was 33.8%. Therefore, clinically staged T1bN0 poorly differentiated esophageal adenocarcinomas are at high risk for upstaging following surgery.


Local noradrenaline release in acute myocardial ischemia: influence of catecholamine synthesis inhibition and beta-adrenoceptor blockade on ischemic injury.
Left coronary artery ligations or sham operations were performed on pentobarbitone-anesthetized rats. The rats were sacrificed at various times after artery occlusion or sham operation and the creatine kinase (CK), potassium (K+), and noradrenaline (NA) content was determined in the left and right ventricular myocardium and in the interventricular septum. One group of rats was pretreated with the NA synthesis inhibitor alpha-methyl-p-tyrosine methyl ester (alpha-MT), another group with d,l-propranolol, and a third group with saline. The NA level of the ischemic left ventricle fell rapidly after the onset of ischemia. This early NA reduction was attenuated after alpha-MT treatment, probably due to reduced transmitter release. Both CK and K+ decreased in a time-dependent manner in the ischemic area of the heart. The early reduction of CK tended to be attenuated after alpha-MT as well as after propranolol. The results support the theory of a detrimental effect of locally released NA. However, in this model the injury produced by the extensive and nearly total ischemia seems so severe that the additional effect of myocardial adrenoceptor activation may well be only marginal.


Prevalence of self-reported allergic rhinitis in eleven major cities in china.
Allergic rhinitis (AR) is a common disease and its prevalence is increasing worldwide. Data on the current prevalence of AR in China, one of the biggest countries in the world, with a population of around 1.3 billion citizens, are scarce. The aim of this study was to investigate the prevalence of self-reported AR in Chinese citizens. In a cross-sectional, population-based study, telephone interviews were conducted in 11 major cities in China after sampling target telephone numbers through the approach of random digital dialing. The questions for the telephone interviews were based on validated questionnaires. A total of 38,203 telephone interviews were conducted from September 2004 to May 2005. The response rate was 63.7%. After adjustment for age and gender, the self-reported prevalence of AR was lowest in Beijing (8.7%) and highest in Urumqi (24.1%). Among the subjects with self-reported AR, 25.6% were diagnosed with persistent AR and 74.4% suffered from intermittent AR. Less than half of the subjects with self-reported AR had presented at a health clinic. In 37.3% AR had previously been diagnosed by physicians, and 33.1% of subjects with self-reported AR had been treated. Comorbidities reported were asthma (9.2%), rhinosinusitis (13.3%) and atopic dermatitis (16.4%). This study demonstrates that the self-reported prevalence of AR in 11 cities across Mainland China has wide variations, ranging from <10% to >20%; 26% of the self-reported AR subjects were classified as suffering from persistent AR.


A focused approach to quality of care assessment in family planning.
An approach to quality of care assessment for family planning based on management-by-objectives has been tested in 18 clinics. Key indicator standards were developed by the family planning agencies themselves and objective survey instruments designed to measure performance against the standards. Results were made available quickly to each clinic and led to operational changes in the majority, with evidence of improved performance and willingness to use evaluation of care as a means for clinic management. Analyses of the aggregated data showed wide variations in performance over several indices of care.


Comparison of 2D and 3D modeled tumor motion estimation/prediction for dynamic tumor tracking during arc radiotherapy.
Many real-time imaging techniques have been developed to localize a target in 3D space or in a 2D beam's eye view (BEV) plane for intrafraction motion tracking in radiation therapy. With tracking system latency, the 3D-modeled method is expected to be more accurate even in terms of 2D BEV tracking error. No quantitative analysis, however, has been reported. In this study, we simulated co-planar arc deliveries using respiratory motion data acquired from 42 patients to quantitatively compare the accuracy between 2D BEV and 3D-modeled tracking in arc therapy and to determine whether 3D information is needed for motion tracking. We used our previously developed low kV dose adaptive MV-kV imaging and motion compensation framework as a representative of 3D-modeled methods. It optimizes the balance between additional kV imaging dose and 3D tracking accuracy and solves the MLC blockage issue. With simulated Gaussian marker detection errors (zero mean and 0.39 mm standard deviation) and ~155/310/460 ms tracking system latencies, the mean percentage of time that the target moved >2 mm from the predicted 2D BEV position are 1.1%/4.0%/7.8% and 1.3%/5.8%/11.6% for the 3D-modeled and 2D-only tracking, respectively. The corresponding average BEV RMS errors are 0.67/0.90/1.13 mm and 0.79/1.10/1.37 mm. Compared to the 2D method, the 3D method reduced the average RMS unresolved motion along the beam direction from ~3 mm to ~1 mm, resulting in on average only <1% dosimetric advantage in the depth direction. Only for a small fraction of the patients, when tracking latency is long, the 3D-modeled method showed significant improvement of BEV tracking accuracy, indicating potential dosimetric advantage. However, if the tracking latency is short (~150 ms or less), those improvements are limited. Therefore, 2D BEV tracking has sufficient targeting accuracy for most clinical cases. The 3D technique is, however, still important in solving the MLC blockage problem during 2D BEV tracking.


Prevalence and emerging resistance of Moraxella catarrhalis in lower respiratory tract infections in Karachi.
To determine the prevalence of Moraxella catarrhalis in sputum cultures from patients with lower respiratory tract infection and their antimicrobial sensitivity profiles. The study comprised sputum specimens of 776 patients at various branches of Dr Essa's Diagnostic Lab, Karachi. The specimens were cultured on blood, chocolate, and eosin methylene blue agars between October 2010 and October 2011. The isolates were identified by conventional methods and anti-biograms were determined by the Kirby-Bauer Agar Disc Diffusion Method. Moraxella catarrhalis was isolated from 39 (5.02%) sputa of which 18 (46.15%) belonged to males. The bimodal age prevalence was 238 (30.7%) in age group 20-29 years, and 180 (23.1%) in 70 years and above. Amoxicillin/clavulanate, cefotaxime, and ceftriaxone were most effective (100%). Very high resistance was seen with amikacin (92.3%), cefixime (92.3%), fosfomycin (84.6%), cefuroxime (84.6%), erythromycin and amoxicillin (76.9%), cotrimoxazole (90%) and doxycycline (76.9%). The incidence of Moraxella catarrhalis in sputum encourages routine culture and sensitivity of sputa from patients suffering from lower respiratory tract infection, especially the elderly and immunocompromised, for tailored drug prescription.


Respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the United States and Finland.
We investigated whether children with a higher respiratory syncytial virus (RSV) genomic load are at a higher risk of more-severe bronchiolitis. Two multicenter prospective cohort studies in the United States and Finland used the same protocol to enroll children aged <2 years hospitalized for bronchiolitis and collect nasopharyngeal aspirates. By using real-time polymerase chain reaction analysis, patients were classified into 3 genomic load status groups: low, intermediate, and high. Outcome measures were a length of hospital stay (LOS) of ≥3 days and intensive care use, defined as admission to the intensive care unit or use of mechanical ventilation. Of 2615 enrolled children, 1764 (67%) had RSV bronchiolitis. Children with a low genomic load had a higher unadjusted risk of having a length of stay of ≥3 days (52%), compared with children with intermediate and those with high genomic loads (42% and 51%, respectively). In a multivariable model, the risk of having a length of stay of ≥3 days remained significantly higher in the groups with intermediate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.20-1.69) and high (OR, 1.58; 95% CI, 1.29-1.94) genomic loads. Similarly, children with a high genomic load had a higher risk of intensive care use (20%, compared with 15% and 16% in the groups with low and intermediate genomic loads, respectively). In a multivariable model, the risk remained significantly higher in the group with a high genomic load (OR, 1.43; 95% CI, 1.03-1.99). Children with a higher RSV genomic load had a higher risk for more-severe bronchiolitis.


Long-Term Gestational Hypoxia Modulates Expression of Key Genes Governing Mitochondrial Function in the Perirenal Adipose of the Late Gestation Sheep Fetus.
We previously reported that long-term hypoxia (LTH) increases expression of brown adipose tissue (BAT) genes in the perirenal adipose in the ovine fetus. The mechanisms with which hypoxia mediates the enhanced BAT phenotype are unresolved. This study was designed to examine the effects of LTH on (1) the expression of endothelial cell nitric oxide synthase (eNOS) and (2) indicators of mitochondrial biogenesis (transcription factors mitochondrial transcription factor A (mtTFA), nuclear respiratory factor (NRF) 1, and NRF-2; cytochrome c oxidase (COX) I, II, and IV and mitochondrial DNA content). Pregnant ewes were maintained at high altitude (3820 m) from ∼40 to 137 to 140 days of gestation and perirenal adipose was collected from normoxic control and LTH fetuses. There was no effect of LTH on fetal body weight or perirenal adipose mass. Long-term hypoxia increased (P < .05) perirenal eNOS and phospho-eNOS, messenger RNA (mRNA) for NRF1, NRF-2, mtTFA as well as COX-I, COX-II, and COX-IV mRNA. In contrast, mRNA for 2 markers for cellular proliferation (Ki67 and proliferating cell nuclear antigen [PCNA]) was lower in perirenal adipose from LTH fetuses compared to controls (P < .05), while mitochondrial to nuclear DNA ratio did not differ between groups. In conclusion, nitric oxide may function as a mechanism via which LTH enhances the BAT phenotype in fetal sheep prior to birth. Although there is an apparent increase in genes supporting mitochondrial function and adaptive thermogenesis in response to LTH, there does not appear to be an increased mitochondrial biogenesis per se. Such adaptive changes may provide a mechanism for the prominence of the BAT phenotype observed in the late gestation LTH fetus.


Atrial shunts: presentation, investigation, and management, including recent advances in magnetic resonance imaging.
Atrial shunts are a common finding in both paediatric and adult populations. Recent developments in advanced imaging have widened the options for diagnosis and evaluation of such shunts. This paper reviews the various types of interatrial communications, discusses the features of clinical presentation in adults and children, and provides an overview of the clinical assessment including physical examination, electrocardiography, echocardiography, cardiac catheterisation, computed tomography, and magnetic resonance imaging. Focus will be placed on recent developments in magnetic resonance imaging that may improve the non-invasive evaluation of atrial shunts.


Near-Infrared Light-Responsive Semiconductor Polymer Composite Hydrogels: Spatial/Temporal-Controlled Release via a Photothermal "Sponge" Effect.
Near-infrared (NIR) light-responsive hydrogels are important for biomedical applications, such as remote-controlled release, but the NIR agents previously used were largely limited to heavy-metal inorganic materials such as gold nanoparticles. In this article, we report a new type of NIR photothermal-responsive hydrogel that can undergo structural changes in response to NIR light for biomedical applications in drug delivery and controlled release. The hydrogels synthesized by integrating a narrow-bandgap semiconductor polymer poly(diketopyrrolopyrrole-alt-3,4-ethylenedioxythiophene) with the polymerization of N-isopropylacrylamide show rapid and reversible mechanical shrinkage upon NIR light irradiation and can serve as carriers for anticancer drug loading and spatial/temporal control of drug release. These stimuli-responsive hydrogels, which can be prepared in different sizes and shapes, integrate photothermal properties and hydrogel characteristics and can provide on-demand, repeated, remote-controlled drug delivery for biomedical applications such as cancer treatment.


The primary preventive study in Uppsala. Fatal and non-fatal myocardial infarction during a 10-year follow-up of a middle-aged male population with treatment of high-risk individuals.
A health survey of middle-aged men was carried out in 1970-73 in the municipality of Uppsala. Subjects with hypertension, hyperlipidaemia, reduced glucose tolerance, and smokers were invited to join various therapy groups. By 1980 this multifactorial intervention programme had thus been running for 10 years. This report describes the results of a follow-up undertaken to evaluate the efficacy of the programme. The annual rate of fatal myocardial infarction (MI) was lower among the participants (n = 2322) in the health examination as well as among participants and non-participants (n = 446) combined than among the male Swedish population of the same age (162 and 187 compared with 296 per 100 000 men, respectively). The annual rate of non-fatal MI among participants and non-participants combined was 295 per 100 000 men, which is lower than in other Swedish cities. In the hypertensive group (n = 126), six men had fatal and seven non-fatal MI. These 13 men had higher blood pressures (BPs) from the start than the other hypertensives. In addition, their BP reduction was smaller than in a control group randomly selected among the hypertensive subjects. In the hyperlipidaemic treatment group (n = 363) there were eight fatal and 10 non-fatal MIs. Nine of these events occurred in individuals who had dropped out from therapy. It is suggested that the low total mortality and the low rates of fatal and non-fatal MI in this middle-aged male population may be related to the multifactorial intervention programme, as the incidences were also low among the treated high-risk groups.


Three new xanthones from Garcinia xanthochymus.
To study xanthones from the barks of Garcinia xanthochymus, the constituents were isolated by normal-phase and reverse-phase silica gel column chromatography from the EtOAc extract. Their structures were elucidated by spectral analysis. Three new xanthones were purified and identified as 1,2,5-trihydroxy-6-methoxyxanthone (1), 1,4,6-trihydroxy-5-methoxyxanthone (2), 1,2,7-trihydroxy-4-(1,1-dimethylallyl) xanthone (3).


Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment.
Tissue engineering aims at resolving problems such as donor shortage and immune rejection faced by transplantation. Scaffolds (artificial extracellular matrices) have critical roles in tissue engineering. Recently, we developed nano-fibrous poly(L-lactic acid) scaffolds under the hypothesis that synthetic nano-fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano-fibrous architecture built in three-dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano-fibrous pore walls adsorbed four times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano-fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same poly(L-lactic acid) material. Furthermore, nano-fibrous scaffolds also allowed >1.7 times of osteoblastic cell attachment than scaffolds with solid pore walls. These results demonstrate that the biomimetic nano-fibrous architecture serves as superior scaffolding for tissue engineering.


Auditory DUM neurons in a bush-cricket: A filter bank for carrier frequency.
In bush-crickets the first stage of central auditory processing occurs in the prothoracic ganglion. About 15 to 50 different auditory dorsal unpaired median neurons (DUM neurons) exist but they have not been studied in any detail. These DUM neurons may be classified into seven different morphological types, although, there is only limited correlation between morphology and physiological responses. Ninety seven percent of the stained neurons were local, 3% were intersegmental. About 90% project nearly exclusively into the auditory neuropile, and 45% into restricted areas therein. Lateral extensions overlap with the axons of primary auditory sensory neurons close to their branching point. DUM neurons are typically tuned to frequencies covering the range between 2 and 50 kHz and thereby may establish a filter bank for carrier frequency. Less than 10% of DUM neurons have their branches in adjacent and more posterior regions of the auditory neuropile and are mostly tuned to low frequencies, less sensitive than the other types and respond to vibration. Thirty five percent of DUM show indications of inhibition, either through reduced responses at higher intensities, or by hyperpolarizing responses to sound. Most DUM neurons produce phasic spike responses preferably at higher intensities. Spikes may be elicited by intracellular current injection. Preliminary data suggest that auditory DUM neurons have GABA as transmitter and therefore may inhibit other auditory interneurons. From all known local auditory neurons, only DUM neurons have frequency specific responses which appear suited for local processing relevant for acoustic communication in bush crickets.


Tropomodulin 1 controls erythroblast enucleation via regulation of F-actin in the enucleosome.
Biogenesis of mammalian red blood cells requires nuclear expulsion by orthochromatic erythoblasts late in terminal differentiation (enucleation), but the mechanism is largely unexplained. Here, we employed high-resolution confocal microscopy to analyze nuclear morphology and F-actin rearrangements during the initiation, progression, and completion of mouse and human erythroblast enucleation in vivo. Mouse erythroblast nuclei acquire a dumbbell-shaped morphology during enucleation, whereas human bone marrow erythroblast nuclei unexpectedly retain their spherical morphology. These morphological differences are linked to differential expression of Lamin isoforms, with primary mouse erythroblasts expressing only Lamin B and primary human erythroblasts only Lamin A/C. We did not consistently identify a continuous F-actin ring at the cell surface constriction in mouse erythroblasts, nor at the membrane protein-sorting boundary in human erythroblasts, which do not have a constriction, arguing against a contractile ring-based nuclear expulsion mechanism. However, both mouse and human erythroblasts contain an F-actin structure at the rear of the translocating nucleus, enriched in tropomodulin 1 (Tmod1) and nonmuscle myosin IIB. We investigated Tmod1 function in mouse and human erythroblasts both in vivo and in vitro and found that absence of Tmod1 leads to enucleation defects in mouse fetal liver erythroblasts, and in CD34+ hematopoietic stem and progenitor cells, with increased F-actin in the structure at the rear of the nucleus. This novel structure, the "enucleosome," may mediate common cytoskeletal mechanisms underlying erythroblast enucleation, notwithstanding the morphological heterogeneity of enucleation across species.


Decision Making as a Learned Skill in Mice and Humans.
Attention is a necessary component in many forms of human and animal learning. Numerous studies have described how attention and memory interact when confronted with a choice point during skill learning. In both animal and human studies, pathways have been found that connect the executive and orienting networks of attention to the hippocampus. The anterior cingulate cortex, part of the executive attention network, is linked to the hippocampus via the nucleus reuniens of the thalamus. The parietal cortex, part of the orienting attention network, accesses the hippocampus via the entorhinal cortex. These studies have led to specific predictions concerning the functional role of each pathway in connecting the cortex to the hippocampus. Here, we review some of the predictions arising from these studies. We then discuss potential methods for manipulating the two pathways and assessing the directionality of their functional connection using viral expression techniques in mice. New studies may allow testing of a behavioral model specifying how the two pathways work together during skill learning.


Knowledge and attitudes about attention-deficit hyperactivity disorder (ADHD): a comparison between practicing teachers and undergraduate education students.
The knowledge and attitudes of practicing teachers regarding ADHD were compared with those of undergraduate education students. Key elements of studies of American and Canadian teachers by Jerome, Gordon, and Hustler (1994) and Jerome, Washington, Laine, and Segal (1999) were replicated. Information was gathered about participants' demographic background (training in ADHD), attitudes towards ADHD, and knowledge about its diagnosis and treatment. Results confirmed the existence of some knowledge gaps, although both practicing teachers and undergraduate education students possessed sound information about ADHD. Misconceptions about ADHD primarily concerned dietary treatment. Attitudes and knowledge were significantly correlated and most participants regarded ADHD as a valid diagnosis with implications for the school setting, and expressed a desire for comprehensive training. Despite similar results for both samples, teachers achieved higher accuracy on knowledge-based questions. These results are discrepant from those of Jerome et al. (1999) who found teachers and students to be similar in factual knowledge. Implications of these findings for curriculum development in academia and in-service teacher training are highlighted.


How fast is protein hydrophobic collapse?
One of the most recurring questions in protein folding refers to the interplay between formation of secondary structure and hydrophobic collapse. In contrast with secondary structure, it is hard to isolate hydrophobic collapse from other folding events. We have directly measured the dynamics of protein hydrophobic collapse in the absence of competing processes. Collapse was triggered with laser-induced temperature jumps in the acid-denatured form of a simple protein and monitored by fluorescence resonance energy transfer between probes placed at the protein ends. The relaxation time for hydrophobic collapse is only approximately equal to 60 ns at 305 K, even faster than secondary structure formation. At higher temperatures, as the protein becomes increasingly compact by a stronger hydrophobic force, we observe a slowdown of the dynamics of collapse. This dynamic hydrophobic effect is a high-temperature analogue of the dynamic glass transition predicted by theory. Our results indicate that in physiological conditions many proteins will initiate folding by collapsing to an unstructured globule. Local motions will presumably drive the following search for native structure in the collapsed globule.


Corticotropin-releasing factor-like immunoreactivity, arginine vasopressin-like immunoreactivity and ACTH-releasing bioactivity in hypothalamic tissue from fetal and neonatal sheep.
Corticotropin-releasing factor-like immunoreactivity (CRF-LI), arginine vasopressin-like immunoreactivity (AVP-LI) and ACTH-releasing bioactivity of hypothalamic tissue from 63- to 143-day-old ovine fetuses and from 7- and 150-day-old lambs have been assessed. CRF-LI and AVP-LI contents and concentrations increased steadily between 63 and 138 days of gestation, decreased at day 143 then rose again in postpartum animals. In terms of concentration, the AVP-LI/CRF-LI ratio remained close to 5 between 63 and 123 days of intrauterine life, decreased steadily in late gestation down to 1.2 at day 143 increased again in lambs. The total hypothalamic ACTH-releasing bioactivity increased 26-fold between 63 and 138 days of gestation and remained constant until day 143. The highest values were observed in 150-day-old-lambs. These data support the view that AVP and oCRF1-41 might be important hypothalamic factors involved in the regulation of ACTH release by the pituitary gland of the sheep fetus. In addition, they suggest that AVP is more important in young fetuses and lambs than in prepartum animals.


Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics.
Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives.


One-step embedding method for maintaining orientation of pathological tissue specimens using agar thin films.
Pathological histology examination involves handling a variety of specimens that are cut according to regulations and placed in cassettes. Tissue fragments in the cassettes are then diagnosed after processing, embedding, thin sectioning, staining and other procedures using a processing machine. Maintaining tissue fragment order and orientation during these processes is important for accurate diagnosis. In this study, we present a method of maintaining tissue fragment order and orientation using a thin film of ultra-high-strength agar and evaluate its usefulness during tissue sectioning.Cassettes were prepared, each containing three pieces of porcine liver, and compared embedding time with and without agar thin films (ATFs). Embedding was performed by three medical laboratory scientists with different levels of experience.To enable one-step tissue sample embedding, ATFs were integrated with samples in the cassettes. This resulted in an average reduction of 6.22 s of embedding time per cassette compared with traditional embedding methods.Through the use of ATFs, tissue fragment order and orientation is maintained, and embedding process time shortened. Additionally, ATFs are easily prepared and stored in 10% neutral buffered formalin over extended periods, allowing for immediate use during sectioning. This method is ideal to implement in busy pathology laboratories.


Atmospheric ozone profiles from high resolution UV spectra obtained with a balloon-borne spectrometer.
High resolution solar spectra at high and low sun angles in the 3200-3400-A region were obtained during balloon flights on 9 Feb. 1977 (altitude 41 km) and 17 Feb. 1977 (altitude 29 km). These data were analyzed using a layer-by-layer three-wavelength differential absorption method. Ozone volume-mixing ratio profiles, which agree with standard profiles, were derived. Suggestions are made for improving the accuracy of the results in future measurements.


[Repair of heel defect with a free medial plantar flap].
The results of reconstruction of plantar heel defects with a local random flap or an island medial plantar flap have in a majority of cases been satisfactory. However, in cases of extensive plantar defects, local tissue transfers are almost impossible. Since 1988, 8 cases with extensive plantar defects have been treated using free medial plantar cutaneous or musculocutaneous flaps. All flaps survived. Six weeks postoperatively, full weight-bearing was obtained and normal activities were resumed. No ulceration in the flaps has been noted in the follow up period between 6 and 24 months, and the two point discrimination was from 20 to 24 mm. The paper particularly points out the importance of nerve repair in the reconstruction, because recovery of the protective sensation is the most important factor to prevent plantar ulceration, and is the basis for good operative results.


Abnormal glucose homeostasis and fasting intolerance in patients with congenital porto-systemic shunts.
In physiological glucose homeostasis, the liver plays a crucial role in the extraction of glucose from the portal circulation and storage as glycogen to enable release through glycogenolysis upon fasting. In addition, insulin secreted by the pancreas is partly eliminated from the systemic circulation by hepatic first-pass. Therefore, patients with a congenital porto-systemic shunt present a unique combination of (a) postabsorptive hyperinsulinemic hypoglycaemia (HH) because of decreased insulin elimination and (b) fasting (ketotic) hypoglycaemia because of decreased glycogenolysis. Patients with porto-systemic shunts therefore provide important insight into the role of the portal circulation and hepatic function in different phases of glucose homeostasis.


Target cell of the polycythemia-inducing Friend virus: studies with myleran.
A single injection of Myleran reduced the pluripotent hematopoietic stem cell, i.e., colony forming unit(s) (CFU), and the erythropoietin-responsive cell (ERC) in polycythemic mice to around 0.5% that of the controls. Repeated injections of erythropoietin (EP) restored ERC populations, whereas the CFU remained at very low levels. This selective action of Myleran and EP in polycythemic mice seemed to be a good approach for the study of oncogenic action of Friend virus on target cells. When the CFU and ERC compartments were decreased, practically no response to the virus was obtained. When there was an appreciable ERC population present with decreased CFU, leukemogenesis still occurred (as judged by the increased spleen weight). This result was in proportion to the dose of EP, i.e., stimulation of the ERC or closely related cells.


A Review of Corneal Transplantation: An Insight on the Overall Global Post-COVID-19 Impact.
The coronavirus disease 2019 (COVID-19) pandemic made us reframe a lot of the strategies followed in medical practice and ophthalmological services and procedures were also not spared, including corneal transplantation or keratoplasty, the most routine procedure performed worldwide. The prevalence of viral presence in the ocular tissue necessitates a focus on the handling of donor ocular tissue and the functioning of eye banks, ensuring it doesn't risk the patient and the doctor's safety. Restrictions in the movement of people during the pandemic limited the number of donations, causing a shortage of tissues, with a large number of people already waitlisted for tissue needs. The lesson from the COVID-19 pandemic directs us to look for long-term corneal storage techniques taking into consideration the tissue viability time and the possibility of post-pandemic shortages. Although there is not a significant number of reports, the cases of corneal graft rejection post-vaccination against COVID-19 are highlighted and thus should form a part of the lookout while evaluating the possible cause of rejection of grafts. This article summarises the overall impact of the pandemic on corneal transplantation and the possible future of storage techniques, which need to evolve and be adapted.


Prevalence of ETV6-RUNX1 fusion gene in children with acute lymphoblastic leukemia in China.
A series of 92 Chinese children newly diagnosed with acute lymphoblastic leukemia (ALL) were examined for the ETV6-RUNX1 (previously TEL-AML1) fusion gene by using a nested reverse transcriptase-polymerase chain reaction. ETV6-RUNX1 fusion transcripts were detected in 21 of 92 patients (22.8%): 16 with common ALL, 4 with precursor B-cell ALL, and 1 with T-ALL. The prevalence of ETV6-RUNX1 positivity was 24.7% (20/81) in childhood B-lineage ALL. The prevalence of ETV6-RUNX1 in Chinese pediatric ALL patients proved to be similar to that found in other countries.


Sediment metal contamination in a creek flowing from a pristine to an industrial area of Trieste Province (Italy).
The following metals: Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined by inductively coupled plasma - atomic emission spectroscopy (ICP-AES) in fluvial sediments of Rosandra Creek, using two different, strong and mild sediment decomposition methods. The purpose was to obtain information about the contamination by metals and distribution paths of pollutants in the area crossed by Rosandra Creek: this little river is the unique epigeous watercourse in the Italian Karst and very few data can be found in literature. In this area, we can find a natural park, but also agricultural activities and an industrial district that was recently defined as "polluted site of national interest". By comparing the results of the strong and mild extraction we have obtained the percentage of extraction and enrichment factors for each metal in the different sediments of the sites R2 and R3 exposed to pollution, while the site R1 was considered as a pristine one because situated in the natural park. The computed enrichment factors are generally not very high, but copper, lead and zinc have factors that require attention. The principal component analysis (PCA) shows that the typically anthropogenic metals (as Cr, Pb, Cu and Zn) constitute the first factor, while the lithogenic metals, as Fe and Ni, constitute the second one; moreover the score plots permit to classify and distinguish the 3 sites: site R3, possibly the more exposed to contamination, has high scores both for anthropogenic and lithogenic metals.


The anaerobic threshold measurement in exercise testing.
The exercise intensity (VO2) above which aerobic energy production starts to be supplemented by anaerobic mechanisms is termed the anaerobic threshold (AT). Lactic acid is produced at an increased rate above this work level. Since this acid is almost completely buffered by HCO-3, the rate of CO2 production increases in excess of that being derived from oxidative metabolism. Thus measurement of this excess CO2, or some reflection of it, can be used during exercise to measure the AT noninvasively. The AT has great physiologic significance, as it demarcates the work rate that the subject can perform for a prolonged period and above which a metabolic acid occurs.


[Bone marrow examination of inherited diseases in children].
Inherited diseases and metabolism inborn errors with hematologic abnormalities such as cytopenias are observed early in the infant or childhood. Most of them require an acute observation of the bone marrow to determine quantitative and qualitative morphological peculiarities of each cell line in order to charatherize cytological signs of these childhood hereditary diseases and differentiate them from acquired disorders, which are particularly frequent in pediatric. So, after a brief review of hematopoietic physiology in healthy neonates and infant, we'll consider the physiopathology and bone marrow aspect of the erythroid (Blackfan-Diamond anemia, congenital dyserythropoietic...), megacaryocytic (Wiskott-Aldrich syndrome, congenital amegakaryocytic thrombocytopenia...) and granulocytic cell line (Kostmann syndrome, WHIM syndrome...) in hereditary disorder. Considering the hematologic consequences of metabolism inborn errors and storage diseases, the last part of this review will be dedicated to the examination of the bone marrow encountered in those diseases such as mitochondrial cytopathy, orotic aciduria or lysinuric aciduria intolerance.


Urinary leakage during sexual intercourse among women with incontinence: Incidence and risk factors.
Coital incontinence is an under-reported disorder among women with urinary incontinence. Women seldom voluntarily report this condition, and as such, related data remains limited and is at times conflicting. To investigate the incidence and quality of life in women with coital incontinence and to determine associated predictors. This observational study involved 505 sexually active women attending the urogynecologic clinic for symptomatic urinary incontinence at a tertiary medical center. All of the patients were consulted about the experience of coital incontinence and completed evaluations including urodynamics, and valid questionnaires including the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, the Urogenital Distress Inventory and the Incontinence Impact Questionnaire. Of these women, 281 (56%) had coital incontinence, while 224 (44%) did not. Among women with coital incontinence, 181 (64%) had urodynamic-proven stress incontinence, 29 (10%) had mixed incontinence, and 15 (5%) had detrusor overactivity. Only 25 (9%) sought consultation for this disorder before direct questioning. Fifty percent (84/281) of the women rarely or sometimes had incontinence during coitus, while 33% (92/281) often had incontinence, and 17% (48/281) always had incontinence. The frequency of coital incontinence was not different regarding the types of incontinence (p = 0.153). Women with mixed incontinence had the worst sexual quality of life and incontinence-related symptom distress. Based on univariate analysis, higher body mass index (OR 2.47, p = 0.027), and lower maximal urethral closure pressure (≤ 30 cmH2O) (OR 4.56, p = 0.007) were possible predictors for coital incontinence. Multivariate analysis showed lower MUCP was independently significant predictors (OR3.93, p = 0.042). The prevalence of coital intercourse in urinary incontinence women was high. Coital incontinence in these women was associated with abnormal urodynamic diagnosis and urethral dysfunction.


Pulmonary manifestations of blastomycosis. Radiological support of a new concept.
The pulmonary manifestations of blastomycosis were observed in 51 patients and correlated with their location in the lungs and the clinical appearance of the patient. Blastomycosis is primarily an airbone infection that occurs in both acute and chronic forms and follows a specific pathway within the lungs. It must be strongly considered in the differential diagnosis of pulmonary lesions in geographical areas endemic to the disease.


Effect of complicated ocular surgery in stress-related parameters: A novel outlook into surgeon's health.
To assess the stress-related physiological parameters of ophthalmic surgeons during complicated cataract surgery and compare them with uncomplicated routine cataract surgery. In this cross-sectional observational study, 110 patients of various types of cataract were divided into two groups: Group 1 included 55 patients with simple cataract (Grade ≤3) with no ocular or systemic comorbidities, whereas Group 2 included 55 patients with complicated cataracts (Grade >3) and ocular/systemic comorbidities. All patients underwent phacoemulsification with intraocular lens implantation in the right eye only. The outcome measures were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and saturation of peripheral oxygen (SpO2). The average SBP, DBP, MAP, and HR were significantly higher in the surgeon operating Group 2 (complicated cataract) compared with Group 1 (uncomplicated cataract; P < 0.05). The average SBP of the surgeon while operating Group 1 patients preoperatively and postoperatively was 125.42 ± 2.49 mmHg and 122.45 ± 2.10 mmHg, respectively, whereas in Group 2, the average SBP of the surgeon taken preoperatively and postoperatively was 145.98 ± 3.80 mmHg and 137.44 ± 3.45 mmHg, respectively (P < 0.05). The surgeon's SpO2 showed no significant difference between the two groups. There is a significant level of increase in stress-related parameters of operating surgeons while doing complicated cataract surgery.


[Management of pure teratoma of the testis in adult, results of a multicenter study over 15 years].
To analyze cases of pure teratoma of the testis (PTT) of a large population-based study, as such tumors are rare, and to make an update on the topic. We retrospectively reviewed the records of patients treated for PTT from 1987 to 2003 in the French Midi-Pyrenees region (southwestern France) and in the Val-de-Grâce military hospital, Paris. Among more than 1000 cases of testis cancer, we identified 20 cases of PTT (4% of the whole population). For each patient, the orchiectomy specimen was reviewed and a clinical and imaging re-evaluation was performed. The pathological re-evaluation revealed non-teratomatous components in three patients (excluded from a following analysis). For the localized PTT patients, four out of eight out of 8 were on surveillance only after the orchiectomy, and the remaining four received adjuvant chemotherapy. None of them received any lymphadenectomy for staging. All patients with the metastatic disease were treated by chemotherapy followed by surgical removal of residual tumor masses. With a mean of 125 months follow-up, 85% of the population did not relapse after treatment. At the last contact, all were alive, without the disease. We confirm that PTT is a malignant disease with a good prognosis. As its management differs from the other non-seminomatous germ cell tumors, the diagnosis of PTT must be with certainty. The retrospective analysis of a series over two decades highlights the deviations from current guidelines. We propose that this rare tumor of young man should be treated in specialized centers to get the optimal management.


[Lichen ruber ulcerosus. Differentiation from Graham-Little syndrome. Pathogenesis and therapy].
A 61-year-old female patient having suffered for several years from typical Graham-Little's syndrome developed lichen ulcerosus after a period of 9 years. We discuss the relationship between these clinical manifestations with special reference to the pathogenesis and distribution of skin lesions in lichen rubber ulcerosus. Among the numerous therapeutic approaches, treatment with chloroquine or dapsone as well as skin grafting seem to be most promising.


Assessment of clinical manifestations, disease activity and organ damage in 996 Korean patients with systemic lupus erythematosus: comparison with other Asian populations.
To describe the clinical manifestations, disease activity and organ damage in Korean patients with systemic lupus erythematosus (SLE). American College of Rheumatology (ACR) criteria, SLE Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinics/ACR damage index (SDI) were assessed in patients with SLE from 1998 to 2012. A total of 996 SLE patients were analyzed. The common accrual of ACR criteria included: immunologic (93%), hematologic (93%), arthritic (66%) and nephritic (50%). In the inception cohort over 10 years of follow-up (n = 120), the number of ACR criteria increased significantly (5.0 ± 1.2 to 5.7 ± 1.3), and nephritis, serositis and neuropsychiatric symptoms tended to increase continuously over time. SLEDAI-2K decreased significantly (5.6 ± 3.4 to 4.1 ± 1.2), but the percentage of patients with SLEDAI scores ≥ 12 did not decrease over time. The common organ damages were musculoskeletal (14.9%) and renal (11.1%). The mean SDI score increased significantly (0.4 ± 0.8 to 1.1 ± 1.6) and renal damage had two peaks in 1 and 6-10 years, musculoskeletal and neuropsychiatric damage were predominant from 1 to 5 years, and ophthalmic damage increased sharply over 10 years. Compared to other Asian cohorts, disease activity was lower and organ damage was less in our Korean cohort. Nephritis, serositis and neuropsychiatric symptoms increased continuously over time. Overall disease activity decreased significantly, but a small portion of severe disease activity continued during the disease course. The most common organ damage was musculoskeletal. The time in organ damage development varied, which reflects the possible causality, such as disease itself and/or treatment.


Variant differentiation patterns in primary liver carcinoma.
Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are two distinct forms of primary liver carcinoma recognizable at the microscope by their architectural and cytological characteristics, as well as specific immunohistochemical profiles. This straightforward concept however, is increasing imperiled by the recognition of primary liver carcinomas that do not subscribe to a dichotomous paradigm of differentiation, and instead demonstrate biphenotypic differentiation, stem/progenitor cell like features or other variant patterns of differentiation. Appropriate nomenclature, diagnostic criteria, prognostic significance and optimal therapeutic approach for these variant tumors are not completely defined, not leasyt because they are not always identified correctly and when they are, lack of uniform terminology hinders collection of adequate number of cases to facilitate their study. Similar to hepatocellular carcinoma and in contrast with intrahepatic cholangiocarcinoma, primary liver tumors showing biphenotypic differentiation, stem/progenitor cell features or variant differentiation occur mainly, but not always, on a background of chronic liver disease. They are particularly frequent after neo-adjuvant therapy. Whether they represent trans-differentiation of malignant cells, or whether they derive from a stem/progenitor cell that gives rise to divergent differentiation remains yet another area of uncertainty.


European definitions, current use, and EMA stance of platelet-rich plasma in sports medicine.
Platelet-rich plasma has been the focus of much attention over the last few years as an appealing biological approach to favor the healing of tissues otherwise doomed by a low healing potential. In Europe, the regulatory framework concerning the blood system is currently disciplined by Directive 2002/98/EC of the European Parliament and Council of January 27, 2003, which sets out quality and safety rules for collecting, controlling, processing, preserving, and distributing human blood and its components, acknowledged in the various States of the Union with internal regulations. This lack of homogeneity in the European legal landscape will probably lead the Community legislature to intervene in the near future, to even out the "rules of engagement" of this peculiar class of biomaterials.


Managing device infections: are we progressing or is infection an insurmountable obstacle?
This article reviews infections that occur in patients with implanted mechanical circulatory support devices and presents recent data for signs of progress in controlling the incidence and impact of these infections. Two types of comparisons are used to examine this question. First, the outcomes of patients with HeartMate vented electric left ventricular assist devices (VADs) (Thoratec Corp, Pleasanton, CA) implanted during the REMATCH Trial are compared with the outcome of more recent patients who received this pump as destination therapy. Second, the outcome of patients who received a smaller left VAD (e.g., an axial flow VAD) or a fully implanted left VAD are reported and contrasted with results from the REMATCH era. Data are presented to support the hypothesis that improvements in patient selection, patient management, device durability, and device design have resulted in lower rates of infection and infection-related death for patients who require mechanical circulatory support.


Sphingosine kinase 1 activation by estrogen receptor α36 contributes to tamoxifen resistance in breast cancer.
In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, nongenomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors, leading to important breast cancer signaling. However, the E2 receptor responsible for SphK1 activation has not yet been identified. Here, we demonstrate in triple-negative breast cancer cells, which lack the canonical ERα66 but express the novel splice variant ERα36, that ERα36 is the receptor responsible for E2-induced activation of SphK1 and formation and secretion of S1P and dihydro-S1P, the ligands for S1PRs. Tamoxifen, the first-line endocrine therapy for breast cancer, is an antagonist of ERα66, but an agonist of ERα36, and, like E2, activates SphK1 and markedly increases secretion of S1P. A major problem with tamoxifen therapy is development of acquired resistance. We found that tamoxifen resistance correlated with increased SphK1 and ERα36 expression in tamoxifen-resistant breast cancer cells, in patient-derived xenografts, and in endocrine-resistant breast cancer patients. Our data also indicate that targeting this ERα36 and SphK1 axis may be a therapeutic option to circumvent endocrine resistance and improve patient outcome.


Association of the Hind III polymorphism with the androgen receptor gene in partial androgen insensitivity syndrome.
Partial androgen insensitivity syndrome (PAIS) is an X-linked disorder resulting from defects in the intracellular androgen receptor (AR). The cloning of the AR cDNA has provided the molecular tools to identify gene abnormalities. Gene deletions being the exception in PAIS, prenatal diagnosis of PAIS resulting from a single base mutation in high risk families is not practical unless the mutation is already known. Brown et al. (1989) reported that 10% of normal X chromosomes present a Hind III 6.7/3.5 kb polymorphism. In this study, we report the association of the Hind II polymorphism in a woman whose son has a PAIS associated with a very low androgen receptor concentration: we differentiated the two maternal X chromosomes and characterized the affected allele. These data demonstrate that the presence of Hind III polymorphic fragments could be used in prenatal diagnosis of androgen insensitivity syndrome in high risk families.


Insecticide susceptibility studies of three cryptic species of the Anopheles balabacensis complex.
Susceptibilities of two colonies of the taxon An. dirus (one from Perlis and from Thailand) and one colony of An. balabacensis from Sabah to DDT, dieldrin, malathion, fenitrothion and propoxur were determined. DDT and fenitrothion tolerance was found in An. dirus species B and An. balabacensis. No resistant strain was isolated as the two colonies were not either homozygous or nearly so for resistance. Field testing of the susceptibility of the adults of An. balabacensis to DDT was carried out between 1957 to 1976. The results indicated a progressive rise in the LC50 levels greater than 1% in almost all instance. The variation in the number of sprays applied in some districts have resulted in varying sensitivities. Association between the changes in levels of DDT susceptibility and exophilic habit of An. balabacensis has been observed but needs further confirmation. The significance of these findings and the difficulties in distinguishing tolerant from truly resistant individuals are discussed in relation to accurate species identification.


The role of the c-Jun N-terminal kinases 1/2 and receptor-interacting protein kinase 3 in furosemide-induced liver injury.
1. The mechanisms of furosemide (FS) hepatotoxicity were explored in mice. Specifically, C57Bl/6 J mice were treated with 500 mg FS/kg bodyweight, and c-Jun N-terminal kinase (JNK) activation and receptor-interacting protein kinase 3 (RIP3) expression were measured by western blotting. Co-treatment with FS and the JNK inhibitor SP600125 was also performed, and FS-induced liver injury was compared in wild-type and RIP3 knockout (KO) mice. 2. JNK phosphorylation and RIP3 expression were increased in livers from the FS-treated mice as early as 6 h after treatment and persisted until at least 24 h. JNK phosphorylation was also observed in primary mouse hepatocytes and human HepaRG cells treated with FS. 3. Phosphorylated JNK translocated into mitochondria in livers, but no evidence of mitochondrial damage was observed. 4. SP600125-treated mice, SP600125 co-treated primary mouse hepatocytes and RIP3 KO mice were not protected against FS hepatotoxicity. These data show that, although JNK activation and RIP3 expression are induced by FS, neither contributes to the liver injury.


Large-scale mercury variations in Lake Vänern (Sweden) 1974-98.
Lake Vänern, the largest lake in Sweden, has been seriously contaminated with mercury during the 20th century. In the 1970's and 80's the direct load, mainly from a chlor-alkali industry in the area, of mercury was drastically reduced as a response to new legislation, from three to five tons down to between five and ten kg yr(-1). Large amounts of the disposed pollutant have accumulated in the sediments. The question posed in this work is now, is the effect of the drastic load reduction after more than two decades visible in the sediments? The question is relevant as large areas still are blacklisted for fishing, but also as a follow-up of a major remedy action. The lake also serves as a freshwater reservoir for even Sweden's second largest city. This work synthesises and compares data of mercury in the sediments from three major field programs, in 1974, 1984 and 1998. The interest is focused on both spatial heterogeneity and temporal trends. In 1974, the surface concentrations are significantly higher than in subsequent surveys. Significant differences are also found between 1984 and 1998. Significant spatial differences within the lake are found for respective year. The most contaminated area is located in the north, close to the major point source (a former chlor-alkali industry). This is also the area with the largest improvement, as a direct response to the reduction in load. Further from the outlet, the recovery is more affected by burial and transport processes out into the deeper basins.


[Progress in genetic research on primary pulmonary hypertension].
Primary pulmonary hypertension (PPH) consisting of hereditary pulmonary arterial hypertension and idiopathic pulmonary arterial hypertension is an obstructive pulmonary hypertension caused by primary pulmonary artery hyperplasia. Both environmental and genetic factors are involved in the pathogenesis of PPH. Genes associated with TGF-β signaling pathway including BMPR2, ALK1, ENG, SMAD8 and other genes including NFU1, CAV1, KCNK3 and TopBPl have been associated with PPH. In this review, the function and mechanism of the above genes in the pathogenesis PPH are summarized.


[The effect of CD8+ cells on isolation and replication of HIV-1].
Human immunodeficiency virus type 1 (HIV-1) seropositive individuals are known to have a population of CD8+T lymphocytes which can suppress the replication of the virus. Two hundred and twelve peripheral blood mononuclear cells (PBMC) samples obtained from 42 seropositive individuals were examined for HIV-1 isolation. HIV-1 recovery rate reached almost 90% by coculture of CD8+ cell-depleted PBMC with uninfected normal PBMC. These results indicated the usefulness of panning method of CD8+ cell for isolation of HIV-1 from asymptomatic carriers (AC). To investigate the suppressive effect of CD8+ cells on HIV-1 replication, we characterized HIV-1 isolates from the same blood samples obtained from five AC individuals before and after the removal of CD8+ cells. Comparative studies of paired isolates revealed significant differences in their replication kinetics in the presence of autologous or allogeneic CD8+ cells. The paired isolates from four out of 5 AC individuals revealed significant differences in their genetic structures, although their biological properties, such as replication rate of cell tropism, were almost the same between the paired isolates. One exception, that of paired isolates from one AC with clinical data of near AIDS-related complex showed a similar genetic structure and similar biological properties. Thus, we showed that many AC individuals during the early clinical stages simultaneously carried two or more replication-competent HIV-ls in vivo which have different genomic backgrounds and sensitivity to the antiviral effects of CD8+ cells.


Immunization for hospital staff.
In this review the recent literature on the topic of immunization of healthcare workers is assessed. The emphasis lies on immunizations that are directly related to the risks of healthcare workers in the workplace. Acceptance of influenza immunization by healthcare workers remains too low, whereas other preventive measures such as hepatitis B vaccination are usually not disputed. Efforts to improve the knowledge of healthcare workers about influenza, its epidemic potential and clinical consequences have contributed to higher immunization rates in some hospitals. Immunization against varicella zoster virus does not result in immunity in all vaccinated persons. This lack of complete protection has infection-control implications, namely the recommendation to wear a mask when caring for clinical cases, regardless of the immunization status. The topic of immunization of healthcare workers has recently been dominated by the discussion of smallpox vaccination, which was promoted by the American public-health authorities for some groups of healthcare workers. Immunization is a preventive measure that is highly cost-effective. Healthcare workers are responsible for the safety and well-being of their patients and should do their utmost to prevent the transmission of infectious pathogens to them. Another positive result of the adherence of healthcare workers to the recommended immunization schedule is the improved self-protection at the workplace. Immunization against some highly contagious infectious agents has been recommended for many years. The list is now being expanded again by the recommendation of smallpox vaccination. Regarding this indication, several questions and safety issues must be resolved in order to positively influence the currently rather sceptical attitude of healthcare workers towards this vaccine.


Screening Characteristics of TIMI Score in Predicting Acute Coronary Syndrome Outcome; a Diagnostic Accuracy Study.
In cases with potential diagnosis of ischemic chest pain, screening high risk patients for adverse outcomes would be very helpful. The present study was designed aiming to determine the diagnostic accuracy of thrombolysis in myocardial infarction (TIMI) score in Patients with potential diagnosis of ischemic chest pain. This diagnostic accuracy study was designed to evaluate the screening performance characteristics of TIMI score in predicting 30-day outcomes of mortality, myocardial infarction (MI), and need for revascularization in patients presenting to ED with complaint of typical chest pain and diagnosis of unstable angina or Non-ST elevation MI. 901 patients with the mean age of 58.17 ± 15.00 years (19-90) were studied (52.9% male). Mean TIMI score of the studied patients was 0.97 ± 0.93 (0-5) and the highest frequency of the score belonged to 0 to 2 with 37.2%, 35.3%, and 21.4%, respectively. In total, 170 (18.8%) patients experienced the outcomes evaluated in this study. Total sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of TIMI score were 20 (95% CI: 17 - 24), 99 (95% CI: 97 - 100), 98 (95% CI: 93 - 100), 42 (95% CI: 39 - 46), 58 (95% CI: 14 - 229), and 1.3 (95% CI: 1.2 - 1.4), respectively. Area under the ROC curve of this system for prediction of 30-day mortality, MI, and need for revascularization were 0.51 (95% CI: 0.47 - 0.55), 0.58 (95% CI: 0.54 - 0.62) and 0.56 (95% CI: 0.52 - 0.60), respectively. Based on the findings of the present study, it seems that TIMI score has a high specificity in predicting 30-day adverse outcomes of mortality, MI, and need for revascularization following acute coronary syndrome. However, since its sensitivity, negative predictive value, and negative likelihood ratio are low, it cannot be used as a proper screening tool for ruling out low risk patients in ED.


Studies on the murine Ss protein: demonstration that the Ss protein is functionally the fourth component of complement.
This report describes a simple and reproducible assay for the fourth component of murine complement (C4). Utilizing this assay, experiments are described which conclusively demonstrate that the murine Ss protein (serum substance) is functional C4 and that ascitic fluid may be used as a source for isolating Ss. The evidence that Ss is functional C4 is: (i) pretreatment of mouse plasma with F(ab')2 anti-Ss completely abrogated the C4 hemolytic titer; and (ii) in the isolation of the Ss protein from ascitic fluid, Ss immunochemical activity and C4 functional activity coeluted in each step of a four-step purification procedure.


Computer simulation of assembly and co-operativity of hexameric AAA ATPases.
AAA ATPases form a functionally diverse superfamily of proteins. Most members form homo-hexameric ring complexes, are catalytically active only in the fully assembled state, and show co-operativity among the six subunits. The mutual dependence among the subunits is clearly evidenced by the fact that incorporation of mutated, inactive subunits can decrease the activity of the remaining wild type subunits. For the first time, we develop here models to describe this form of allostery, evaluate them in a simulation study, and test them on experimental data. We show that it is important to consider the assembly reactions in the kinetic model, and to define a formal inhibition scheme. We simulate three inhibition scenarios explicitly, and demonstrate that they result in differing outcomes. Finally, we deduce fitting formulas, and test them on real and simulated data. A non-competitive inhibition formula fitted experimental and simulated data best. To our knowledge, our study is the first one that derives and tests formal allosteric schemes to explain the inhibitory effects of mutant subunits on oligomeric enzymes.


Prevention of Dexmedetomidine on Postoperative Delirium and Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Thoracoscopic Lobectomy.
To investigate the effect of dexmedetomidine on postoperative cognitive function and delirium in elderly patients undergoing thoracoscopic lobectomy. 109 elderly patients (age is more than 65 years) who underwent thoracoscopic lobectomy in our hospital from June 2020 to Feb 2022 were randomly divided into the dexmedetomidine (DEX) group (n = 54) and the control group (n = 55). The patients in the experimental group were given dexmedetomidine by intravenous pump, intravenous pump 0.5 μg/kg within 10 minutes, and maintained the speed of 0.5 μg/(kg. h) to 30 min before the operation was ended. The control group was given the same amount of normal saline. Delirium assessment-severity (CAM-S) assessment and Mini-Cog were used to assess the severity levels of POD and POCD 24 h before, 6 hours after, one day after the operation, three days after the operation, and 1 week after the operation. Serum TNF-αα and NSE levels were assessed by using enzyme-linked immunosorbent assay. NRS pain marks were assessed in the DEX group at postanesthesia care unit (PACU) and 24 postoperation. Surgical pierhysmographic index (SPI) evaluation was performed at five time points. The Mini-Cog scores in the DEX group were markedly enhanced compared with those in the saline group 6 and 24 hours after the operation. The SPI values in the DEX group were markedly reduced within 2 min after intubation and at surgical sutures. Moreover, the CAM scores in the DEX group were markedly reduced 24 hours after the operation. Tumor necrosis factor-α (TNF-α) and neuron-specific enolase (NSE) levels were significantly decreased in the DEX group at T1∼T3. The use of dexmedetomidine in the thoracoscopic lobectomy in elderly patients could reduce the occurrence and severity of postoperative cognitive dysfunction and delirium.


Same-Day Imaging Using Small Proteins: Clinical Experience and Translational Prospects in Oncology.
Imaging of expression of therapeutic targets may enable stratification of patients for targeted treatments. The use of small radiolabeled probes based on the heavy-chain variable region of heavy-chain-only immunoglobulins or nonimmunoglobulin scaffolds permits rapid localization of radiotracers in tumors and rapid clearance from normal tissues. This makes high-contrast imaging possible on the day of injection. This mini review focuses on small proteins for radionuclide-based imaging that would allow same-day imaging, with the emphasis on clinical applications and promising preclinical developments within the field of oncology.


Cystic fibrosis: present status and future prospects in detection of patients and carriers.
Development of a sensitive, easily performed, reliable test would be an important advance in detecting cystic fibrosis, improving genetic counselling and providing early effective treatment. The sweat chloride test, which is reliable in diagnosis, is technically too difficult for a screening program, and only reliably detects homozygotes. In contrast, the meconium test for detecting homozygote newborns is simple, inexpensive, reasonably specific but its general application has yet to be evaluated. Detection of serum components is the basis of two new tests to distinguish patients with cystic fibrosis and carriers. The effect of these serum components on ciliary activity is the principle of one test, an extremely difficult procedure that is subjective and lacks sufficient specificity for routine use. The second test, in which serum components are separated by isoelectric focusing, may provide an objective biochemical means of detecting both homozygotes and heterozygotes.


Electrical Impedance Tomography for Robot-Aided Internal Radiation Therapy.
High dose rate brachytherapy (HDR) is an internal based radiation treatment for prostate cancer. The treatment can deliver radiation to the site of dominant tumor growth within the prostate. Imaging methods to delineate the dominant tumor are imperative to ensure the maximum success of HDR. This paper investigates the feasibility of using electrical impedance tomography (EIT) as the main imaging modality during robot-aided internal radiation therapy. A procedure utilizing brachytherapy needles in order to perform EIT for the purpose of robot-aided prostate cancer imaging is proposed. It is known that cancerous tissue exhibits different conductivity than healthy tissue. Using this information, it is hypothesized that a conductivity map of the tissue can be used to locate and delineate cancerous nodules via EIT. Multiple experiments were conducted using eight brachytherapy needle electrodes. Observations indicate that the imaging procedure is able to observe differences in tissue conductivity in a setting that approximates transperineal HDR and confirm that brachytherapy needles can be used as electrodes for this purpose. The needles can access the tissue at a specific depth that traditional EIT surface electrodes cannot. The results indicate the feasibility of using brachytherapy needles for EIT for the purpose internal radiation therapy.


Mice do not respond with delayed hypersensitivity to penicillin-derived determinants.
Penicillin structures of varying lipophilicity were used to induce delayed hypersensitivity (DH) in different strains of mice. Epicutaneous application on inflamed skin or intracutaneous or subcutaneous injection with Freund's complete adjuvant did not induce DH, despite the fact that picrylchloride readily produced such responses. Sheep, rabbit and mouse red cells as well as mouse lymph node and epidermal cells conjugated with various amounts of penicillin injected subcutaneously in the base of the tail did not induce a DH reaction to penicillin either, whereas such responses to other cellular components and also to the TNP determinant after using picryl sulphonic acid conjugated spleen cells were recorded. Since the mice in other studies have been shown to respond with antibodies to soluble penicilloyl protein conjugates, but never to penicillin itself, we concluded that this species of animal is incapable of responding to penicillin with DH.


The relationship between semantic short-term memory and immediate serial recall of known and unknown words and nonwords: data from two Chinese individuals with aphasia.
The present study investigated verbal recall of semantically preserved and degraded words and nonwords by taking into consideration the status of one's semantic short-term memory (STM). Two experiments were conducted on 2 Chinese individuals with aphasia. The first experiment showed that they had largely preserved phonological processing abilities accompanied by mild but comparable semantic processing deficits; however, their performance on STM tasks revealed a double dissociation. The second experiment found that the participant with more preserved semantic STM had better recall of known words and nonwords than of their unknown counterparts, whereas such effects were absent in the patient with severe semantic STM deficit. The results are compatible with models that assume separate phonological and semantic STM components, such as that of R. C. Martin, M. Lesch, and M. Bartha (1999). In addition, the distribution of error types was different from previous studies. This is discussed in terms of the methodology of the authors' experiments and current views regarding the nature of semantic STM and representations in the Chinese mental lexicon.


Factorial Invariance within Longitudinal Structural Equation Models: Measuring the Same Construct across Time.
Charting change in behavior as a function of age and investigating longitudinal relations among constructs are primary goals of developmental research. Traditionally, researchers rely on a single measure (e.g., scale score) for a given construct for each person at each occasion of measurement, assuming that measure reflects the same construct at each occasion. With multiple indicators of a latent construct at each time of measurement, the researcher can evaluate whether factorial invariance holds. If factorial invariance constraints are satisfied, latent variable scores at each time of measurement are on the same metric and stronger conclusions are warranted. In this paper we discuss factorial invariance in longitudinal studies, contrasting analytic approaches and highlighting strengths of the multiple-indicator approach to modeling developmental processes.


Wrongful termination: lessons from the Geron clinical trial.
Geron Corporation is a publically traded company that launched a phase I clinical trial of a human embryonic stem cell-based therapy for spinal cord injury. The company enrolled the first patient in October 2010 and stopped the trial 1 year later. The fifth patient had been enrolled but not transplanted when the company announced the trial's end. After discussions with clinical staff and family, an agreement was reached to add her to the cohort and proceed with the transplant. Two and half years later, the research is still waiting to restart. With this background in mind, we discuss the major ethical and social questions raised by the Geron case. We offer recommendations for institutional review boards and clinical sites as they deliberate approvals of early-phase trials in frontier medicine.


Gastric outlet obstruction caused by microperforation of Helicobacter pylori-related antral ulcer.
We report a Helicobacter pylori-related antral gastric ulcer that continued to cause symptoms despite H. pylori eradication. The patient had progressive gastric outlet obstruction, raising the possibility of a malignancy. On exploratory laparotomy, he was found to have a large inflammatory mass surrounding a contained microperforation.


Surgical Versus Non-surgical Treatment of Unstable Lateral Compression Type I (LC1) Injuries of the Pelvis With Complete Sacral Fractures in Non-fragility Fracture Patients: A Systematic Review.
Lateral compression type 1 (LC1) injuries comprise two-thirds of pelvic fractures. Approximately one-third of LC1 fractures are unstable and may benefit from surgical fixation to improve stability but it is not clear if this leads to better clinical or cost-effectiveness outcomes. This study explores differences in patient-reported outcomes, complications, time-to-mobilisation, cost-effectiveness, and length of hospital stay between surgically and non-surgically treated unstable LC1 non-fragility fractures. We performed a systematic review to determine whether surgical or non-surgical treatment yielded better clinical and cost-effectiveness outcomes for the treatment of unstable LC1 pelvic injuries with complete sacral fractures, excluding fragility fractures. We searched Medline, Embase and Cochrane databases from inception to June 2022, as well as clinical trial registries. A formal meta-analysis was not possible due to available study designs and heterogeneity. Therefore, a narrative review of the findings has been provided. Five observational studies met the inclusion criteria. A total of 183 patients were treated surgically, and 314 patients were treated non-surgically. Patients treated surgically had lower pain levels (Visual Analogue Scale) and fewer days to mobilisation. Quality of life (EuroQol-5 domains and 36-Item Short Form questionnaires) was better in the surgical group, but not statistically significant. No statistical differences in the length of hospital stay or complication rates were found. This review highlights the low quantity and quality of existing data on patients with unstable LC1 pelvic fractures and the need for a definitive randomised controlled trial to determine whether surgical or non-surgical care should be the preferred treatment concerning clinical and cost-effective care.


Quantitative analysis of platelet alpha v beta 3 binding to osteopontin using laser tweezers.
To determine whether platelet adhesion to surfaces coated with the matrix protein osteopontin requires an agonist-induced increase in the affinity of the integrin alpha v beta 3 for this ligand, we used laser tweezers to measure the rupture force between single alpha v beta 3 molecules on the platelet surface and osteopontin-coated beads. Virtually all platelets stimulated with 10 microM ADP bound strongly to osteopontin, producing rupture forces as great as 100 piconewtons (pN) with a peak at 45-50 pN. By contrast, 90% of unstimulated, resting non-reactive platelets bound weakly to osteopontin, with rupture forces rarely exceeding 30-35 pN. However, approximately 10% of unstimulated platelets, resting reactive platelets, exhibited rupture force distributions similar to stimulated platelets. Moreover, ADP stimulation resulted in a 12-fold increase in the probability of detecting rupture forces >30 pN compared with resting non-reactive platelets. Pre-incubating stimulated platelets with the inhibitory prostaglandin E1, a cyclic RGD peptide, the monoclonal antibody abciximab, or the alpha v beta 3-specific cyclic peptide XJ735 returned force histograms to those of non-reactive platelets. These experiments demonstrate that ADP stimulation increases the strength of the interaction between platelet alpha v beta 3 and osteopontin. Furthermore, they indicate that platelet adhesion to osteopontin-coated surfaces requires an agonist-induced exposure of alpha v beta 3-binding sites for this ligand.