Hypothalamic pathways involved in metabolic regulatory functions, as identified by track-tracing methods.
The present review of the fiber connections of the hypothalamus has been concerned basically with recent data obtained by the aid of the autoradiographic and HRP tracer techniques. Evidence presented has shown that, besides confirming many of the older data, recent studies have resulted in the introduction of several conceptual modifications into the classic picture of hypothalamic hodological relationships. Among these conceptual modifications, the following can be mentioned: (1) the medially placed nuclei of the hypothalamus have a great number of long efferent and afferent connections with many extrahypothalamic structures; (2) many hypothalamic nuclei send direct projections to cell territories in the brainstem and spinal cord that contain preganglionic autonomic motor neurons; (3) several neural districts that lie caudal to the mesencephalon send direct projections to the hypothalamus; (4) in addition to the olfactory channel, other sensory pathways (including interoceptive and gustatory conduction lines) have a relatively direct access to hypothalamic mechanisms; (5) the hypothalamus sends fibers to several brainstem territories that give rise to widespread monoaminergic projections; and (6) there are anatomical pathways that establish reciprocal connections between the hypothalamus and the basal ganglia. Some of the possible physiological correlates of these anatomical findings in the context of metabolic regulatory functions have been briefly indicated.


The importance of computed tomography (CT) scans in the early diagnosis of Gorham-Stout Disease - A case report.
Gorham Stout disease (GSD) or vanishing bone disease is an infrequent entity in clinical practice characterized by gross and progressive bone loss along with excessive growth of vascular and lymphatic tissue. Very little is known about the pathogenesis of GSD, which makes the diagnosis challenging. Due to the rarity of the disease, no treatment guidelines have been created yet. We report a case of GSD in a 53-year-old male patient. He presented with bone pain and initial imaging showed widespread osteolytic lesions in the cervical and mid thoracic spine, ribs, sternum, clavicles, scapula and humerus. Two percutaneous bone biopsies were performed, followed by an open spine biopsy of the L2 spinous processes for histological examination. Unfortunately, no diagnosis was established. Although, he was treated symptomatically, he kept enduring pain and presented again after seven months. His laboratory values were out of the normal range which prompted thorough investigations. New imaging and bone biopsy revealed multiple osteolytic lesions and vascular lesions with cavernous morphology. GSD was diagnosed after ruling out a neoplastic process and confirming the cavernous morphology with immunohistochemical stain. He was treated symptomatically with immunomodulators, bisphosphonates and supplements. Regular follow-up with a specialist was recommended. We hope this case will raise awareness of GSD in common clinical practice and shed some insight on its clinical presentation and the role CT and other imaging modalities play in the diagnosis of GSD.


Improving the TFold test for differential shotgun proteomics.
We present an updated version of the TFold software for pinpointing differentially expressed proteins in shotgun proteomics experiments. Given an FDR bound, the updated approach uses a theoretical FDR estimator to maximize the number of identifications that satisfy both a fold-change cutoff that varies with the t-test P-value as a power law and a stringency criterion that aims to detect lowly abundant proteins. The new version has yielded significant improvements in sensitivity over the previous one. Freely available for academic use at http://pcarvalho.com/patternlab.


Suicidal Ideation among Veterans Living with Cancer Referred to Mental Health.
Objectives: Eliminating Veteran suicide is a top priority for the Department of Veterans' Affairs (VA). This study identified factors associated with suicidal ideation (SI) among a rarely studied subgroup of Veterans: those with cancer.Methods: Veterans (age M = 61.83) with cancer (N= 175) referred for psychological evaluation completed measures of pain, sleep, depressive, anxiety, and PTSD symptoms. SI was defined by endorsing on paper-and-pencil questionnaire thoughts of killing oneself in the past 2 weeks or during clinical interview.Results: 25.1% reported SI. Compared to those without SI, Veterans with SI had higher ratings on measures of depression, anxiety, and PTSD symptoms. History of suicide attempt(s) was included in the model due to clinical significance. Logistic regression was performed with these variables as predictors of SI. The omnibus model was significant (p< .001). However, only anhedonia and depressed mood had a statistically significant contribution to the model (β = 0.540, p= .001).Conclusions: Anhedonia and depressed mood predicted SI among Veterans with cancer above and beyond other risk factors.Clinical Implications: This study's findings highlight the importance of incorporating suicide risk screenings in oncology clinics across VA medical centers.


Decreased sperm survivability in subfertile Delaware roosters as indicated by comparative and competitive fertilization.
Duration of fertility following intravaginal and intramagnal insemination of hens with viable spermatozoa from subfertile Delaware roosters was compared with that obtained with spermatozoa from fertile Leghorns and subfertile Wyandotte roosters. In contrast to results with Leghorn and Wyandotte birds, duration of fertility was not increased following intramagnal insemination of spermatozoa from Delaware birds. Competitive fertilization also demonstrated that duration of fertility was less than expected in the spermatozoa from Delaware birds. Heritable subfertility in Wyandotte and Delaware roosters therefore appears to be attributable to distinct sperm defects.


Effects of solid-phase mass transfer on the performance of a stirred anaerobic sequencing batch reactor containing immobilized biomass.
This work reports on experiments for an anaerobic sequencing batch reactor containing immobilized biomass which aimed at verifying the effects of solid-phase mass transfer on the reactor's overall performance. Four experiments were carried out at 30 degrees C with cubic polyurethane foam particles previously inoculated with anaerobic biomass. Different solid-phase mass transfer conditions were reached in each experiment by varying the size of the bioparticle from 0.5 to 3.0 cm. The reactor was fed with a low-strength synthetic wastewater containing protein, carbohydrates and lipid and the effects of mass transfer were evaluated through dynamic substrate concentration profiles during 8-hour batch cycles. A modified first-order kinetic model provided a good representation of the behavior of the dynamic concentration profiles. The solid-phase mass transfer was found to slightly affect the concentration of effluent organic matter expressed as chemical oxygen demand (COD). The concentration of residual effluent substrate increased as the size of the bioparticle was increased. The cycle time was not affected as the size of the bioparticle was increased from 0.5 to 2.0 cm. However, it was found that the cycle time in a reactor with 3.0-cm cubic particles should be higher than that required in systems with smaller particles. The apparent first-order kinetic parameter was estimated as 0.59+/-0.01 h(-1) for experiments with bioparticle sizes ranging from 0.5 to 2.0 cm, while a value of 0.48 h(-1) was obtained in the experiment with 3.0-cm bioparticles.


A feasibility study to investigate the effect of functional electrical stimulation and physiotherapy exercise on the quality of gait of people with multiple sclerosis.
To examine the effect of Functional Electrical Stimulation (FES) for dropped foot and hip instability in combination with physiotherapy core stability exercises. Twenty-eight people with secondary progressive multiple sclerosis and unilateral dropped foot participated in a randomized crossover trial. Group1 received FES for correction of dropped foot for six weeks with the addition of hip extension for a further six weeks. In weeks 12-18, FES was continued with the addition of eight sessions of core stability physiotherapy with home-based exercise. FES and home-based exercise were continued until weeks 19-24. Group 2 received the same physiotherapy intervention over the first 12 weeks, adding FES in the second 12 weeks. FES improved walking speed and Rivermead Observational Gait Analysis (ROGA) score, whereas physiotherapy did not. Adding gluteal stimulation further improved ROGA score. Both interventions reduced falls, but adding FES to physiotherapy reduced them further. FES had greater impact on Multiple Sclerosis Impact Scale, MSIS-29. The intervention was feasible. FES for dropped foot may improve mobility and quality of life and may reduce falls. Adding gluteal stimulation further improved gait quality. Adding physiotherapy may have enhanced the effect of FES, but FES had the dominant effect.


Krüppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer.
Krüppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR, Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial-mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC. The relationship between KLF8 expression and various clinicopathological features or EMT markers was investigated. The results showed m-RNA and protein of KLF8 were overexpressed in NSCLC and the percent of KLF8 positive cells was positively correlated with TNM stage, lymph node metastasis and poor overall survive. Moreover, high expression of KLF8 correlated with E-cadherin low expression, and Vimentin overexpression. Additionally, COX multivariate regression analysis suggested that TNM stage, KLF8, E-cadherin and Vimentin were independent prognostic indicators for overall survival of patients with NSCLC. The data demonstrate that KLF8 is overexpressed in NSCLC. KLF8 overexpression promotes the malignancy of NSCLC, which mechanism may be involved in EMT. KLF8 maybe serve as a potential therapeutic target for NSCLC.


Genital tract infections and infertility.
Infectious agents can impair various important human functions, including reproduction. Bacteria, fungi, viruses and parasites are able to interfere with the reproductive function in both sexes. Infections of male genito-urinary tract account for about 15% of the case of male infertility. Infections can affect different sites of the male reproductive tract, such as the testis, epididymis and male accessory sex glands. Spermatozoa themselves subsequently can be affected by urogenital infections at different levels of their development, maturation and transport. Among the most common microorganisms involved in sexually transmitted infections, interfering with male fertility, there are the Chlamydia trachomatis and Neisseria gonorrhoeae. Less frequently male infertility is due to non-sexually transmitted epididymo-orchitis, mostly caused by Escherichia coli. In female, the first two microorganisms are certainly involved in cervical, tubal, and peritoneal damage, while Herpes simplex cervicitis is less dangerous. The overall importance of cervical involvement is still under discussion. Tubo-peritoneal damage seems to be the foremost manner in which microorganisms interfere with human fertility. C. trachomatis is considered the most important cause of tubal lacerations and obstruction, pelvic inflammatory disease (PID) and adhesions. N. gonorrhoeae, even though its overall incidence seems to decline, is still to be considered in the same sense, while bacterial vaginosis should not be ignored, as causative agents can produce ascending infections of the female genital tract. The role of infections, particularly co-infections, as causes of the impairment of sperm quality, motility and function needs further investigation. Tropical diseases necessitate monitoring as for their diffusion or re-diffusion in the western world.


Eigenvector centrality and its variability over time are promising indicators of alterations in brain function due to early amyloid deposition.
This scientific commentary refers to 'Eigenvector centrality dynamics are related to Alzheimer's disease pathological changes in non-demented individuals', by Lorenzini et al. (https://doi.org/10.1093/braincomms/fcad088).


IMplementing best practice post-partum contraceptive services through a quality imPROVEment initiative for and with immigrant women in Sweden (IMPROVE it): a protocol for a cluster randomised control trial with a process evaluation.
Immigrant women's challenges in realizing sexual and reproductive health and rights (SRHR) are exacerbated by the lack of knowledge regarding how to tailor post-partum contraceptive services to their needs. Therefore, the overall aim of the IMPROVE-it project is to promote equity in SRHR through improvement of contraceptive services with and for immigrant women, and, thus, to strengthen women's possibility to choose and initiate effective contraceptive methods post-partum. This Quality Improvement Collaborative (QIC) on contraceptive services and use will combine a cluster randomized controlled trial (cRCT) with a process evaluation. The cRCT will be conducted at 28 maternal health clinics (MHCs) in Sweden, that are the clusters and unit of randomization, and include women attending regular post-partum visits within 16 weeks post birth. Utilizing the Breakthrough Series Collaborative model, the study's intervention strategies include learning sessions, action periods, and workshops informed by joint learning, co-design, and evidence-based practices. The primary outcome, women's choice of an effective contraceptive method within 16 weeks after giving birth, will be measured using the Swedish Pregnancy Register (SPR). Secondary outcomes regarding women's experiences of contraceptive counselling, use and satisfaction of chosen contraceptive method will be evaluated using questionnaires completed by participating women at enrolment, 6 and 12 months post enrolment. The outcomes including readiness, motivation, competence and confidence will be measured through project documentation and questionnaires. The project's primary outcome involving women's choice of contraceptive method will be estimated by using a logistic regression analysis. A multivariate analysis will be performed to control for age, sociodemographic characteristics, and reproductive history. The process evaluation will be conducted using recordings from learning sessions, questionnaires aimed at participating midwives, intervention checklists and project documents. The intervention's co-design activities will meaningfully include immigrants in implementation research and allow midwives to have a direct, immediate impact on improving patient care. This study will also provide evidence as to what extent, how and why the QIC was effective in post-partum contraceptive services. NCT05521646, August 30, 2022.


Diphtheritic septicaemia and probable endocarditis: a case report and review of the literature.
Corynebacterium diphtheriae usually produces an infection limited to the respiratory tract and the organisms rarely invade the blood stream. We report the case of a 6-year-old girl who, 2 months after an unsuccessful repair of a ventricular septal defect, developed septicaemia with non-toxigenic C. diphtheriae. The organism appeared resistant to penicillin in vitro and failed to respond to a course of trimethoprim-sulfamethoxazole to which it was susceptible in the laboratory. A cure was finally achieved using cephalothin and gentamicin, followed by an additional course of ampicillin and amoxicillin. Twelve previously recorded cases of diphtheritic sepsis and endocarditis are reviewed.


Effect of blenderized tube feeds on gastric emptying: A retrospective cohort study.
Blenderized tube feeds (blends) are associated with lower hospital admissions and reduced gastroesophageal symptoms, but their high viscosity may theoretically prolong gastric emptying. Our objective was to compare differences in gastric emptying with blends vs with formula. We retrospectively identified individuals 6 months to 20 years with enteral tubes who underwent 1-h liquid gastric emptying scintigraphy from 1998 to 2020 at Boston Children's Hospital. Examinations were excluded if a postpyloric tube was present, tracer was administered orally or with diet differing from habitual, habitual diet was indeterminable, imaging was terminated early, or >50% of input counts emptied during bolus administration. Emptying was classified as delayed if gastric residual at 1 h was ≥60% of ingested dose. Eighteen examinations (15 individuals) were performed with blends and 35 examinations (32 individuals) with formula. Although percentage of residual at 1 h was significantly higher in patients receiving blends compared with formula (54 ± 17 vs 40 ± 25, P = 0.04), the number of patients with delayed gastric emptying did not differ (39% vs 29%, respectively, P = 0.54). Type of diet, feed volume or concurrent medications did not predict delayed gastric emptying. Children with blends received higher bolus volumes (106 ± 55 vs 66 ± 59 ml; P = 0.02), and this significantly predicted percentage of residual (β = 0.14; P = 0.01). The proportion of patients with delayed gastric emptying was similar in children receiving blends and formula. Although the mean percentage of gastric residual was higher with blends, this may be explained by higher bolus volumes administered. This preliminary work suggests that blends compare favorably to formula.


Total Endovascular Aortic Arch Repair Using 3-Vessel Inner Branch Stent Graft.
Endovascular repair has been introduced to decrease the morbidity and mortality associated with open surgical repair of aortic arch pathology. This case illustrates a 71-year-old male patient with an asymptomatic saccular aortic arch aneurysm treated by total endovascular aortic repair using 3-vessel inner branch stent graft. Postoperative course was unremarkable, and the patient was discharge home on postoperative day 3. Total endovascular aortic arch repair is a suitable alternative in higher-risk patients with aortic arch aneurysms who are not ideally suited for open surgical repair.


Evaluation and statistical optimization of methane oxidation using rice husk amended dumpsite soil as biocover.
A laboratory scale study was conducted to investigate the effect of rice husk amended biocover to mitigate the CH4 emission from landfills. Various physico-chemical and environmental variables like proportion of amended biocover material (rice husk), temperature, moisture content, CH4 concentration, CO2 concentration, O2 concentration and incubation time were considered in the study which affect the CH4 bio-oxidation. For the present study, sequential statistical approach with Placket Burman Design (PBD) was used to identify significant variables, having influential role on CH4 bio-oxidation, from all variables. Further, interactive effect of four selected variables including rice husk proportion, temperature, CH4 concentration and incubation time was studied with Box-Behnken Design (BBD) adopting Response Surface Methodology (RSM) to optimize the conditions for CH4 oxidation. In this study, the maximum CH4 oxidation potential of 76.83μgCH4g(-1)dwh(-1) was observed under optimum conditions with rice husk amendment of 6% (w/w), 5h incubation time at 40°C temperature with 40% (v/v) initial CH4 concentration. The results for CH4 oxidation potential also advocated the suitability of rice husk amendment in biocover system to curb emitted CH4 from landfills/open dumpsite over conventional clay or sand cover on supplying CH4 and O2 to microbes on maintaining proper aeration.


Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer?
The aims of this study are to investigate the actual time from primary surgery for epithelial ovarian cancer (OC) to initiation of chemotherapy (TI) amongst Danish women in 2005-2006, and to compare the survival for groups with early initiation (≤median TI) and late initiation of adjuvant chemotherapy (>median TI). All Danish women who underwent surgery for OC in the period 1 January 2005 to 31 December 2006 and recorded in the Danish Gynaecological Cancer Database (DGCD) were included. The five-year survival was estimated overall and by TI exposure. The Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR). The median TI was 32days (25-75% quartile: 24days; 41days). The strongest prognostic factors for death were residual tumour and the International Federation of Obstetrics and Gynecology (FIGO) stage. The unadjusted HR for death in patients with TI>32days compared with TI≤32days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39), p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%). This nationwide population-based cohort study revealed a non-significant increased risk of death for patients with TI>32days compared with the reference TI≤32days. The strongest prognostic factors were residual tumour after surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%; 46.5%).


Automatic stenosis recognition from coronary angiography using convolutional neural networks.
Coronary artery disease, which is mostly caused by atherosclerotic narrowing of the coronary artery lumen, is a leading cause of death. Coronary angiography is the standard method to estimate the severity of coronary artery stenosis, but is frequently limited by intra- and inter-observer variations. We propose a deep-learning algorithm that automatically recognizes stenosis in coronary angiographic images. The proposed method consists of key frame detection, deep learning model training for classification of stenosis on each key frame, and visualization of the possible location of the stenosis. Firstly, we propose an algorithm that automatically extracts key frames essential for diagnosis from 452 right coronary artery angiography movie clips. Our deep learning model is then trained with image-level annotations to classify the areas narrowed by over 50 %. To make the model focus on the salient features, we apply a self-attention mechanism. The stenotic locations are visualized using the activated area of feature maps with gradient-weighted class activation mapping. The automatically detected key frame was very close to the manually selected key frame (average distance (1.70 ± 0.12) frame per clip). The model was trained with key frames on internal datasets, and validated with internal and external datasets. Our training method achieved high frame-wise area-under-the-curve of 0.971, frame-wise accuracy of 0.934, and clip-wise accuracy of 0.965 in the average values of cross-validation evaluations. The external validation results showed high performances with the mean frame-wise area-under-the-curve of (0.925 and 0.956) in the single and ensemble model, respectively. Heat map visualization shows the location for different types of stenosis in both internal and external data sets. With the self-attention mechanism, the stenosis could be precisely localized, which helps to accurately classify the stenosis by type. Our automated classification algorithm could recognize and localize coronary artery stenosis highly accurately. Our approach might provide the basis for a screening and assistant tool for the interpretation of coronary angiography.


Assessment of the FreeStyle Libre 2 interstitial glucose monitor in hypo- and euglycemic cats.
Continuous glucose monitoring systems have been validated for eu- and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). Assess FSL2 accuracy in cats with hypoglycemia. Nine healthy, purpose-bred cats. Hyperinsulinemic-hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland-Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P < .05 considered significant). Overall, BG and IG correlated strongly (r = 0.83, P < .0001) in stable glycemia and moderately at all rates of change (r = 0.69, P < .0001). Interstitial glucose concentration underestimated BG in euglycemia, but the BG-IG difference was progressively smaller as BG decreased (12.9 ± 12.2, 8.8 ± 11.2, -3.2 ± 7.4, and -7.8 ± 5.2 mg/dL in the ranges of 80-120 [n = 64], 60-79 [n = 29], 50-59 [n = 71], and 29-49 mg/dL [n = 53], respectively). Although IG underestimates BG throughout most of the hypo-euglycemic range, IG generally overestimates BG in marked hypoglycemia (<60 mg/dL). It is therefore imperative to evaluate FSL2 results in this critical range with caution.


Subacute toxicity study of patulin in the rat: effects on the kidney and the gastro-intestinal tract.
Female and male Wistar rats were given drinking-water containing patulin at concentrations of 0, 24, 84 or 295 mg/litre citrate buffer (1 mM) for 4 wk. Compared with the controls, there were decreases in food and liquid intake by rats given the mid and high doses of patulin and the body weights of rats in the high-dose group were also decreased. The creatinine clearance in the high-dose group was lowered, although morphological glomerular damage was not observed. In the high-dose group, fundic ulcers in the stomach and enlargement and activation of the pancreatico-duodenal lymph nodes were noticed, while villous hyperaemia in the duodenum was observed in the mid- and high-dose groups. From the present data it can be concluded that high doses of patulin, administered via the drinking-water, caused effects on the kidney and gastro-intestinal tract. Since no changes in the relative weight or histological appearance of the adrenal glands were observed, it is suggested that the fundic ulcers in the stomach were caused by a direct effect of patulin and not indirectly (i.e. by stress).


Acute nitric oxide synthase inhibition induces greater increases in blood pressure in female versus male Wistar Kyoto rats.
Nitric oxide (NO) contributes to blood pressure (BP) regulation via its vasodilatory and anti-inflammatory properties. We and others previously reported sex differences in BP in normotensive and hypertensive rat models where females have lower BP than age-matched males. As females are known to have greater NO bioavailability than age-matched males, the current study was designed to test the hypothesis that anesthetized female normotensive Wistar Kyoto rats (WKY) are more responsive to acute NOS inhibition-induced increases in BP compared to male WKY. Twelve-week-old male and female WKY were randomized to infusion of the nonspecific NOS inhibitor NG -nitro-L-arginine methyl ester (L-NAME, 1 mg/kg/min) or selective NOS1 inhibition with vinyl-L-NIO (VNIO, 0.5 mg/kg/min) for 60 min. Mean arterial BP, glomerular filtration rate (GFR), urine volume, and electrolyte excretion were assessed before, and during L-NAME or VNIO infusion. L-NAME and VNIO significantly increased BP in both sexes; however, the increase in BP with L-NAME infusion was greater in females versus males compared to baseline BP values. Acute infusion of neither L-NAME nor VNIO for 60 min altered GFR in either sex. However, urine volume, sodium, chloride and potassium excretion levels increased comparably in male and female WKY with L-NAME and VNIO infusion. Our findings suggest sex differences in BP responses to acute non-isoform-specific NOS inhibition in WKY, with females being more responsive to L-NAME-induced elevations in BP relative to male WKY. However, sex differences in the BP response did not coincide with sex differences in renal hemodynamic responses to acute NOS inhibition.


Transient displacement induced in shear wave elastography: comparison between analytical results and ultrasound measurements.
It is now accepted that an effective way to investigate the elastic properties of soft tissues is to generate a localized transient acoustic radiation force and to follow the associated displacements in the time/space domain. Shear waves induced by this stress field are particularly interesting in this kind of medium because they are governed by the shear elastic modulus mu, which is directly linked to the Young modulus, and spatial distribution and temporal evolution of the transient motion induced must therefore be obtained in detail. We report here a model based on the elastodynamic Green's function formalism to describe these displacements. 3D simulation of radiation force in homogenous elastic media was performed and the displacement curves computed at different radial distances for different temporal force profiles. Amplitude and duration of displacement were found to be reliable parameters to characterize the elastic properties of the medium. Experimental measurements were performed in a homogeneous agar-gelatin tissue-mimicking phantom, and two transducers were used to generate the radiation force and follow the induced displacements. Displacements obtained from different lateral locations around the applied force axis were then used to reconstruct the shear-wave propagation in a scan plane as a function of time. The experimental displacements/curves agreed with the theoretical profiles obtained by the elastodynamic Green's function formalism.


Effects of Mauritia flexuosa L. f. buriti oil on symptoms induced by Bothrops moojeni snake envenomation.
In Brazil, there are species of snakes that become involved in accidents and cause serious health problems to the inhabitants, highlighting the genus Bothrops for being responsible for approximately 90% of accidents reported annually. In the northern region of the country, this genus is responsible for the largest number of accidents, especially among rural dwellers. These populations invest in alternative treatments for with the purpose of improving the symptoms caused by snakebites. The species Mauritia flexuosa L. f., known as buriti, is traditionally used for the treatment of envenomation by snakes. This study aimed to evaluate the antiophidic potential of the oil of Mauritia flexuosa L. f. for Bothrops moojeni H. venom, confronting cultural and scientific knowledge. The physicochemical properties were determined, and the components present in the oil, extracted from fruit pulp, were analyzed by Gas Chromatography Coupled with Mass Spectrometry. The in vitro inhibitory capacity of the oil for phospholipase, metalloprotease and serine protease activities was investigated. In the in vivo studies, male Swiss mice were used to evaluate the effect of oil on lethality and toxicity, and hemorrhagic, myotoxic and edematogenic activities were assessed. GC‒MS analysis identification of 90.95% of the constituents of the oil, with the main components being 9-eicosenoic acid, (Z)- (34.54%), n-hexadecanoic acid (25.55%) and (E)-9-octadecenoic acid ethyl ester (12.43%). For the substrates, the outcomes indicate that the oil inhibited the activity of the main classes of toxins present in Bothrops moojeni H. venom (VBm) at the highest dose tested (0.5 μL), with inhibition of 84% for the hydrolysis of the selective substrate for serine protease and inhibition of 60% for the hydrolysis of substrates for PLA2 and metalloproteases. The antiophidic activity in vivo was evaluated with two concentrations of the oil: 1.5 mg, the dosage the population, diluted in mineral oil to a volume of 1 tablespoon and 15 mg, administered by gavage 30 min before poisoning and at time zero (concomitant to poisoning), and both concentrations administered by gavage in combination with topical use at time zero. The bleeding time in the group treated with oil at a concentration of 15 mg administered at time zero was significantly lower than that in the control group (p < 0.05). However, a greater inhibition of bleeding time was observed when local application was combined with the gavage treatment at both concentrations tested at time zero (p < 0.05). In the myotoxicity test, oil was efficient in reducing the myotoxic effects induced by the venom at the two concentrations tested, with gavage administration at time zero and gavage plus topical administration at time zero (p < 0.05). The data obtained show that the oil is safe to use at the concentrations studied and contains fatty acids that may collaborate for cellular-level repair of the injuries caused by Bm poisoning. The in vitro and in vivo experiments showed that oil inhibits the main proteolytic enzymes present in the venom and that it has important activities to control the local effects caused by bothropic venom.


Increased central serotonergic activity associated with nocturnal anorexia induced by Walker 256 carcinoma.
The role of brain serotonin levels in Walker 256 tumor induced anorexia was investigated. Total and free plasma tryptophan, regional brain serotonin and 5-hydroxyindoleacetic acid were determined at night, and their relationship to nocturnal anorexia assessed by linear regression analysis. No significant difference in tryptophan, serotonin, or 5-hydroxyindoleacetic acid levels was detected between pair fed and tumor bearing rats exhibiting a 20% reduction of nighttime food intake. Tumor bearing rats with a 40% reduction in food intake had higher nighttime plasma free tryptophan and regional 5-hydroxyindoleacetic acid levels than their pair fed malnourished controls. These results indicate that increased plasma free tryptophan and elevated serotonin metabolism may not be the initial dysfunction responsible for nocturnal anorexia. However, it may contribute to the decreasing nocturnal food intake in severely anorexic tumor rats.


Cooperative gating of chloride channel subunits in endothelial cells.
New methods are described to detect subconductance levels and to analyse ion channel gating. These methods are applied to simulated and experimental data. Single chloride channel records from inside-out membrane patches excised from human umbilical venous endothelial cells (HUVEC) exhibit, in addition to the full closed and full open configurations, intermediate subconductance levels which are multiple of an elementary conductance of 112.5 pS. Analysis of transitions from one state to another and the comparison of real data with simulated data leads to the proposal of a cooperative model of gating for the observed subunits of a chloride channel.


Targeting the multifunctional HBV core protein as a potential cure for chronic hepatitis B.
The core (capsid) protein of hepatitis B virus (HBV) is the building block of nucleocapsids where viral DNA reverse transcriptional replication takes place and mediates virus-host cell interaction important for the persistence of HBV infection. The pleiotropic role of core protein (Cp) in HBV replication makes it an attractive target for antiviral therapies of chronic hepatitis B, a disease that affects more than 257 million people worldwide without a cure. Recent clinical studies indicate that core protein allosteric modulators (CpAMs) have a great promise as a key component of hepatitis B curative therapies. Particularly, it has been demonstrated that modulation of Cp dimer-dimer interactions by several chemical series of CpAMs not only inhibit nucleocapsid assembly and viral DNA replication, but also induce the disassembly of double-stranded DNA-containing nucleocapsids to prevent the synthesis of cccDNA. Moreover, the different chemotypes of CpAMs modulate Cp assembly by interaction with distinct amino acid residues at the HAP pocket between Cp dimer-dimer interfaces, which results in the assembly of Cp dimers into either non-capsid Cp polymers (type I CpAMs) or empty capsids with distinct physical property (type II CpAMs). The different CpAMs also differentially modulate Cp metabolism and subcellular distribution, which may impact cccDNA metabolism and host antiviral immune responses, the critical factors for the cure of chronic HBV infection. This review article highlights the recent research progress on the structure and function of core protein in HBV replication cycle, the mode of action of CpAMs, as well as the current status and perspectives on the discovery and development of core protein-targeting antivirals. This article forms part of a symposium in Antiviral Research on "Wide-ranging immune and direct-acting antiviral approaches to curing HBV and HDV infections."


Development of cell-expressed and virion-incorporated CCR5-targeted vaccine.
Our previous study demonstrated that the immunization with a cycloimmunogen derived from extracellular loop-2 (ECL-2) of CCR5 (cDDR5) attenuated acute phase of CCR5-tropic simian-human immunodeficiency virus (SHIV)(SF162P3) replication in vivo. Although the study showed that the antisera raised against cDDR5 reacted with cell-expressed CCR5, we have not yet demonstrated whether the antisera can react with virion-incorporated CCR5. Here, we show that rhesus cDDR5 (rcDDR5)-specific antibodies react with not only cell-expressed but also virion-incorporated simian CCR5s (siCCR5s), but may predominantly exert their inhibitory effects on simian immunodeficiency virus (SIV) infection by the binding of cell-expressed rather than virion-incorporated CCR5s. These results suggest that the virion-incorporated CCR5 may contribute to the reactivation of the anti-rcDDR5 antibody-producing B-cells by SIV particles after rcDDR5 immunization, although the binding of anti-rcDDR5 antibody to virion-incorporated CCR5 results in a partial inhibitory effect on SIV infection.


[Deficiency of folates in pregnancy: effect of supplementary folic acid].
Higher folate needs are present during pregnancy, which may lead to tissular deficiency in the mother and to depleted newborn folate reserves. The aim of this work was to assess the prevalence of folate deficiency and to establish the rates of serum and red cell folate in two groups of mothers and newborn infants, one receiving only iron and the other iron and folate during pregnancy. The rates of serum and red cell folate found at the end of pregnancy were significantly higher in the group which received folate; however, the percentage of cases with tissular folate deficiency was low in both groups, with no significant difference (3.8% and 1.3%, respectively). These findings, along with the lack of effect of supplemental folate on erythropoiesis, pose some questions on the usefulness of supplemental folate during pregnancy in our country.


Assessment of guide fitting using an intra-oral scanner: An in vitro study.
The aim of this study was to evaluate the capacity of an intra-oral scanner (IOS) to assess the position of an endodontic guide in vitro. Fourteen extracted human teeth were placed into a maxillary model and scanned using computed tomography and a reference laboratory scanner. An ideal endodontic guide was then created and modified by adding defects of different thicknesses to simulate incorrect positions: 50 μm, 150 μm, 400 μm, and 1000 μm. For each thickness, guides were printed three times and each guide was scanned by three experimented operators using a Trios 4 IOS (3Shape, Copenhagen, Denmark). The 36 scans were compared using a best-fit alignment to the master model without defect to define the accuracy of the method and the positioning error. The IOS presented a mean trueness of 1.28 μm (SD= 12.70) and a mean precision of 11.52 μm (SD= 62.17). Considering all sizes of defect, the mean measured position of the endodontic guide was highly correlated (R>0.99) with the expected position. Compared to the ideal guide, there was a mean linear deviation of 46.11 μm (SD= 23.21) and a mean angular deviation of 5.9° (SD= 1.2); this deviation was not influenced by the operator. The present study found that an IOS had good performance to detect a positioning error of the endodontic guide in vitro. This new application of IOS has a promising potential in clinical practice to assist practitioners during the fitting of guides.


Altered performance of schizophrenia patients in an auditory detection and discrimination task: exploring the 'self-monitoring' model of hallucination.
It has been suggested that perceptual hallucination results from a bias in attributing a self-generated event to an external source. The 'self-monitoring' model proposes that the impairment arises from a defective corollary discharge in perceptual decisions. However, psychophysical studies in schizophrenia patients have not found consistent support for the model. We re-explored this issue by including subjects with mood disorders as patient controls and employed signals of variable intensities in an auditory detection and discrimination task. Using signal detection theory, we found decreased sensitivity in auditory detection and discrimination in schizophrenia patients, as compared to control subjects. Moreover, the psychometric functions of schizophrenics had a shallower slope than those of the controls. According to the uncertainty theory of signal detection, this suggested that schizophrenia patients monitored a smaller number of perceptual channels. On the other hand, hallucinating and non-hallucinating schizophrenia patients did not differ from each other, nor did they as a group differ from control subjects in terms of response bias. Overall, our results do not support the idea that hallucination results from an altered bias in the online processing of perceptual signals.


Neurological research in Europe, as assessed with a four-year overview of neurological science international journals.
This paper analyses all the peer-reviewed articles published by European authors in 161 neurological journals screened by ISI in accordance with Current Contents/Life Science and Current Contents/Clinical Medicine in the period 1995-1998. Our aim was to report the amount and quality of neurological research in the different countries of the European Union (EU), the USA and the world. The number of papers, the impact factors (IF), the population of the source country and gross domestic product (GDP), were downloaded. Data show that in the EU there is a progressive increase in the number of published papers from 1995 to 1998 and that large countries such as Germany, the United Kingdom, France and Italy rank at the top four places for absolute number of papers. The gap in the number of papers between the USA and the EU significantly diminished in the examined period, from a difference of 14 % to 6 %. However, when the IF is considered, the USA performed better than EU, although excellent results have been obtained by the United Kingdom, Ireland, Netherlands and Sweden. When the number and quality of papers are plotted against the number of inhabitants or GDP, Sweden, the Netherlands and Finland are the leading countries in Europe. The present study demonstrates that neurological research in the EU is active and productive, is steadily increasing and is now a relevant part of all biomedical world research.


Formation of an RNA heterodimer upon heating of nodavirus particles.
Flock House virus is a small icosahedral insect virus of the family Nodaviridae. Its genome consists of two positive-sense RNA molecules, which are believed to be encapsidated into a single viral particle. However, evidence to support this claim is circumstantial. Here we demonstrate that exposure of nodavirus particles to heat causes the two strands of viral RNA to form a stable complex, directly establishing that both RNAs are copackaged into one virion. The physical properties of the RNA complex, the effect of heat on the particles per se, and the possible relevance of these findings to the nodavirus life cycle are presented.


The Association of Religion and Spirituality with Obesity and Weight Change in the USA: A Large-Scale Cohort Study.
The association between religion, spirituality, and body weight is controversial, given the methodological limitations of existing studies. Using the Nurses' Health Study II cohort, follow-up occurred from 2001 to 2015, with up to 35,547 participants assessed for the religious or spiritual coping and religious service attendance analyses. Cox regression and generalized estimating equations evaluated associations with obesity and weight change, respectively. Religious or spiritual coping and religious service attendance had little evidence of an association with obesity. Compared with not using religious or spiritual coping at all, the fully adjusted hazard ratios (HRs) were minimally different across categories: a little bit (HR = 1.05, 95% CI: 0.92-1.18), a medium amount (HR = 1.09, 95% CI: 0.96-1.24), and a lot (HR = 1.10; 95% CI: 0.96-1.25) (Ptrend = 0.17). Compared with participants who never or almost never attend religious meetings or services, there was little evidence of an association between those attending less than once/month (HR = 1.08, 95% CI: 0.97-1.10), 1-3 times/month (HR = 1.01, 95% CI: 0.90-1.13), once/week (HR = 0.92, 95% CI: 0.83-1.02), and more than once/week (HR = 0.94, 95% CI: 0.82-1.07) (Ptrend = 0.06). Findings were similar for weight change. There was no significant association between religious or spiritual coping, religious service attendance, obesity, and weight change. While religion and spirituality are prominent in American society, they are not important psychosocial factors influencing body weight in this sample.


The epidemiology of hepatitis B infection in housestaff.
Ninety-nine medical and surgical house officers were prospectively evaluated during internship and residency for the development of hepatitis B virus (HBV) infection. The overall incidence of hepatitis B was 10.2% per year. Eighty-six percent of episodes were subclinical. The greatest risk factor appeared to be frequent hand-to-mouth activity such as smoking or licking requisition labels. The presence of a hemodialysis or transplantation unit may be an additional institutional risk factor. HBV infection was not associated with a history of needle-sticks or contact with known antigen-positive patients. Educational efforts to minimize HBV infection should concentrate on handwashing techniques and discouragement of hand-to-mouth activity in patient care areas.


Structural change of G-quartet by 5'-elongation of telomere DNA oligomer.
Structural change of G-quartet formed by telomere G-rich DNA oligomers are investigated by NMR and CD spectroscopy. G-quartet structure changes depending on the length of 5'-terminal sequence.


An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Vascular dementia is usually sporadic and associated with definite risk factors. Several cases also occur in a familial fashion, and may affect middle-aged or even younger subjects. Recently, an autosomal dominant inheritance was demonstrated in two unrelated French families, the members of which were affected by stroke-like episodes culminating in progressive dementia. Genetic linkage analysis assigned the disease locus to chromosome 19q12. We report an additional kindred of Italian origin in which at least 16 subjects presented leukoencephalopathic alterations. Recurrent strokes, psychiatric disturbances, dementia, and in 2 members, tetraplegia and pseudobulbar palsy were the hallmarks of this syndrome. Notably, 5 asymptomatic individuals had neuroradiological signs of leukoencephalopathy. Pathological examination of 1 subject revealed a widespread vasculopathy of the perforating arterioles, characterized by deposition of eosinophilic-congophilic material that did not immunostain with antibodies against prion protein, beta-amyloid, cystatin C, transthyretin, or heat-shock protein 70 and was similar to that described in the French families. Based on the maximum lod score, the most likely location for the disease locus was also mapped to chromosome 19q12, and found to coincide with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) locus. The present results confirm the existence of a nosologically distinct, autosomal dominant cerebrovascular disease, presenting with recurrent subcortical ischemic strokes independent of vascular risk factors.


Ventricular noncompaction: Over or under diagnosis?
Ventricular noncompaction (VNC) describes a cardiomyopathy characterized by excessive myocardial trabeculations and deep intertrabecular recesses. Detection rates are increasingly rising and the frequency of NVC has changed from a disease that is thought to be rare to that described as 'relatively common'. However, there had been a number of un-answered questions regarding the clinical and echocardiographic features of VNC. In this review we discuss the frequency of VNC and emphasize its distinctive clinical features and associations.


Candidate stress biomarkers for queen failure diagnostics.
Queen failure is a persistent problem in beekeeping operations, but in the absence of overt symptoms it is often difficult, if not impossible, to ascertain the root cause. Stressors like heat-shock, cold-shock, and sublethal pesticide exposure can reduce stored sperm viability and lead to cryptic queen failure. Previously, we suggested candidate protein markers indicating heat-shock in queens. Here, we further investigate these heat-shock markers and test new stressors to identify additional candidate protein markers. We found that heat-shocking queens for upwards of 1 h at 40 °C was necessary to induce significant changes in the two strongest candidate heat-shock markers, and that relative humidity significantly influenced the degree of activation. In blind heat-shock experiments, we tested the efficiency of these markers at assigning queens to their respective treatment groups and found that one marker was sufficient to correctly assign queens 75% of the time. Finally, we compared cold-shocked queens at 4 °C and pesticide-exposed queens to controls to identify candidate markers for these additional stressors, and compared relative abundances of all markers to queens designated as 'healthy' and 'failing' by beekeepers. Queens that failed in the field had higher expression of both heat-shock and pesticide protein markers, but not cold-shock markers. This work offers some of the first steps towards developing molecular diagnostic tools to aid in determining cryptic causes of queen failure. Further work will be necessary to determine how long after the stress event a marker's expression remains elevated, and how accurate these markers will be for field diagnoses.


NADH-dependent reduction of D-proline in Clostridium sticklandii. Reconstitution from three fractions containing NADH dehydrogenase, D-proline reductase, and a third protein factor.
The enzyme system from Clostridium sticklandii catalyzing the NADH-dependent reduction of D-proline was co-purified by chromatography on DEAE-cellulose at pH 8.2 and ammonium sulfate fractionation, and resolved into fractions containing three different protein components, NADH dehydrogenase, D-proline reductase and a third protein factor, by chromatography on DEAE-cellulose at pH 7.0. Upon recombination of the fractions containing the three different protein components, the NADH-dependent reduction of D-proline was successfully reconstituted. The NADH dehydrogenase fractions oxidized NADH in the presence of artificial electron acceptors, and were inhibited by p-hydroxymercuriphenylsulfonate (50% at 80 nM). They contained 3--4 different enzyme bands as revealed by polyacrylamide-gel electropherograms stained with the NADH-dependent reduction of 2,3,5-triphenyltetrazolium chloride. D-Proline reduction was also coupled to a leuco-methylene blue-generating system containing D-glucose and glucose-oxidase (EC 184.108.40.206). Circumstantial evidence indicated that, among the clostridial proteins, only D-proline reductase and the third protein factor were needed for this reaction.


Mortality and morbidity in scleroderma renal crisis: A systematic literature review.
The objective of this study was to systematically review the mortality and morbidity associated with scleroderma renal crisis and to determine temporal trends. We searched MEDLINE, Embase and the Cochrane Database of Systematic Reviews from database inception to 10 February 2020. Bibliographies of selected articles were hand-searched for additional references. Data were extracted using a standardized extraction form. Study quality was assessed using the Newcastle-Ottawa scale. Results were analysed qualitatively. Twenty studies with 14,059 systemic sclerosis subjects, of which 854 had scleroderma renal crisis and 4095 had systemic sclerosis-associated end-stage renal disease, met inclusion criteria. Study quality was generally moderate. Cumulative mortality in the post-angiotensin-converting enzyme inhibitor era was approximately 20% at 6 months, 30%-36% at 1 year, 19%-40% at 3 years and almost 50% at 10 years from scleroderma renal crisis onset. Although the introduction of angiotensin-converting enzyme inhibitors in the early 1970s resulted in a 50% improvement in scleroderma renal crisis mortality, there was no further improvement thereafter. Scleroderma renal crisis mortality rates were proportionally higher than mortality rates associated with other systemic sclerosis organ involvement. The rate of permanent dialysis after scleroderma renal crisis in the post-angiotensin-converting enzyme inhibitor era ranged from 19%-40%. Three to 17% of systemic sclerosis patients underwent renal transplant. Survival was better in patients post-renal transplant (54%-91%) compared to those on dialysis (31%-56%). Graft survival improved over time and appeared similar to that of patients with other types of end-stage renal disease. While there has been considerable improvement in scleroderma renal crisis-related outcomes since the introduction of angiotensin-converting enzyme inhibitors, morbidity and mortality remain high for affected patients without convincing evidence of further improvement in the post-angiotensin-converting enzyme inhibitor era. Novel treatments are required to improve outcomes of scleroderma renal crisis.


Long-Term Beta-Blocker Therapy in Patients With Stable Coronary Artery Disease After Percutaneous Coronary Intervention.
It is unclear whether beta-blocker treatment is advantageous in patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). We evaluated the clinical impact of long-term beta-blocker maintenance in patients with stable CAD after PCI with drug-eluting stent (DES). From a nationwide cohort database, we identified the stable CAD patients without current or prior history of myocardial infarction or heart failure who underwent DES implantation. An intention-to-treat principle was used to analyze the impact of beta-blocker treatment on long-term outcomes of major adverse cardiovascular events (MACE) composed of cardiovascular death, myocardial infarction, and hospitalization with heart failure. After stabilized inverse probability of treatment weighting, a total of 78,380 patients with stable CAD was enrolled; 45,746 patients with and 32,634 without beta-blocker treatment. At 5 years after PCI with a 6-month quarantine period, the adjusted incidence of MACE was significantly higher in patients treated with beta-blockers [10.0 vs. 9.1%; hazard ratio (HR) 1.11, 95% CI 1.06-1.16, p < 0.001] in an intention-to-treat analysis. There was no significant difference in all-cause death between patients treated with and without beta-blockers (8.1 vs. 8.2%; HR 0.99, 95% CI 0.94-1.04, p = 0.62). Statistical analysis with a time-varying Cox regression and rank-preserving structure failure time model revealed similar results to the intention-to-treat analysis. Among patients with stable CAD undergoing DES implantation, long-term maintenance with beta-blocker treatment might not be associated with clinical outcome improvement. ClinicalTrial.gov (NCT04715594).


Pulsatile ocular blood flow and intraocular pressure during retrobulbar injection of lignocaine: influence of additives.
To assess the influence of adrenaline and hyaluronidase on pulsatile ocular blood flow and intraocular pressure changes during retrobulbar anesthesia. Patients undergoing cataract surgery under local anesthesia received a 5-mL retrobulbar injection of lignocaine with either adrenaline, hyaluronidase, or no addition. Continuous pneumotonometry was performed using the OBF tonograph (OBF Labs, Chippenham, UK), which automatically derives pulsatile ocular blood flow values. Measurements were taken before and one minute after injection, and changes were compared between groups to evaluate the effects of changing the constituents of the injection. There was a marked decrease in pulsatile ocular blood flow during injection in all groups. In the group receiving lignocaine with hyaluronidase, the decrease in pulsatile ocular blood flow (mean -141 microL/min) was significantly less than in either the group receiving lignocaine and adrenaline (mean -249 microL/min) or the group receiving lignocaine alone (mean -245 microL/min). There was no significant change in intraocular pressure in any group. Hyaluronidase appears to lessen the reduction in pulsatile ocular blood flow. Injection volumes of 5 mL need not cause significant intraocular pressure change.


WormTensor: a clustering method for time-series whole-brain activity data from C. elegans.
In the field of neuroscience, neural modules and circuits that control biological functions have been found throughout entire neural networks. Correlations in neural activity can be used to identify such neural modules. Recent technological advances enable us to measure whole-brain neural activity with single-cell resolution in several species including [Formula: see text]. Because current neural activity data in C. elegans contain many missing data points, it is necessary to merge results from as many animals as possible to obtain more reliable functional modules. In this work, we developed a new time-series clustering method, WormTensor, to identify functional modules using whole-brain activity data from C. elegans. WormTensor uses a distance measure, modified shape-based distance to account for the lags and the mutual inhibition of cell-cell interactions and applies the tensor decomposition algorithm multi-view clustering based on matrix integration using the higher orthogonal iteration of tensors (HOOI) algorithm (MC-MI-HOOI), which can estimate both the weight to account for the reliability of data from each animal and the clusters that are common across animals. We applied the method to 24 individual C. elegans and successfully found some known functional modules. Compared with a widely used consensus clustering method to aggregate multiple clustering results, WormTensor showed higher silhouette coefficients. Our simulation also showed that WormTensor is robust to contamination from noisy data. WormTensor is freely available as an R/CRAN package https://cran.r-project.org/web/packages/WormTensor .


Health status changes with transitory disability over time.
The six-question disability set from the American Community Survey serves as the national standard for measuring disability across all surveys conducted by the U.S. Department of Health and Human Services. These questions are intended to identify people who experience a long-term disability, and data from these questions are frequently interpreted as capturing discrete groups of individuals. Recent research has shown that a significant proportion of individuals respond to these questions inconsistently over time, possibly indicating that the six-question set also identifies transitory disability. However, it is unclear if these inconsistent responses are associated with changes in health status. We begin to test the validity of these observations by exploring how changes in health related quality of life correspond to changes in disability status. We recruited 525 participants to complete a longitudinal paper and pencil survey four times over 18 months that included the six disability questions, measures of health related quality of life, and mobility equipment use. We computed within person changes in health related quality of life variables to investigate how changes in disability status are associated with changes in health status. Among respondents who reported disability, half or less consistently reported the same disability. Additionally, respondents who changed disability responses also reported changes in health related quality of life. For example, when individuals transition into walking disability, their health-related quality of life index decreases by, on average, 0.18 s.d. (p<0.05), and when individuals transition out of walking disability their health-related quality of life index increases by, on average, 0.27 s.d. (p<0.001). The six-question set identifies people who experience both enduring and transitory disability. Changes in health related characteristics correlate with changes in disability status. This suggests that observed transitions in disability reflect real changes in perceived health and impairment.


Possible mechanism of CHI3L1 promoting tonsil lymphocytes proliferation in children with obstructive sleep apnea syndrome.
The typical characteristic of pediatric obstructive sleep apnea syndrome (OSAS) is systemic inflammation and adenotonsillar hypertrophy (ATH), but the inflammatory markers and mechanism of adenotonsillar proliferation are unclear. IHC, qPCR, and western blotting were used to identify the expression of CHI3L1 in the tonsils of children with OSAS. The primary tonsil lymphocytes (PTLCs) from children with OSAS were cultured and recombinant human CHI3L1 protein was added to culture media. After the stimulation with CHI3L1 protein of different concentrations and time points, lymphocyte proliferation was assessed by CCK-8 kits and flow cytometry. The activation of ERK1/2 and the effects on the proliferation of PTLCs were observed by western blotting. The expression of CHI3L1 was higher in the OSAS group than in the PS group. CHI3L1 (100 ng/mmol for 24 h) resulted in a significant increase in the proliferation rate. The ERK1/2 activator (PMA) promoted the proliferation of PTLCs and inhibitor AG126 significantly inhibited proliferation. CHI3L1 can promote the proliferation of tonsil lymphocytes via ERK1/2 pathways. This result indicates that CHI3L1 may play an important role in the pathogenesis of OSAS in children. Inhibition of CHI3L1 or ERK1/2 may be potential therapeutic targets for CHI3L1-induced proliferation in childhood OSAS. CHI3L1 may be an inflammatory marker in childhood OSAS. CHI3L1 can promote the proliferation of PTLCs in a concentration and time-dependent condition. CHI3L1 can promote the proliferation of tonsil lymphocytes via ERK1/2 pathways.


Frequency of ventricular fibrillation as predictor of one-year survival from out-of-hospital cardiac arrests.
This study determined whether electrocardiographic analysis of ventricular fibrillation (VF) can predict 1-year survival from bystander-witnessed, out-of-hospital cardiac arrests of cardiac origin. VF was analyzed using fast-Fourier transformation in a community in which emergency medical technicians delivered shock with an automated external defibrillator before arrival to the hospital. The frequency of VF can predict survival 1 year after hospital discharge from shock-delivered, bystander-witnessed cardiac arrests of cardiac etiology.


Evaluation of treatment efficacy in patients with minimal nasal septum deviation and concha bullosa using the nasal obstruction symptom evaluation scale.
This study aims to compare the treatment efficacy of middle turbinate lateral lamella resection alone with septoplasty plus middle turbinate lateral lamella resection for nasal stuffiness in two patient groups using the nasal obstruction symptom evaluation (NOSE) scale in patients with concomitant minimal nasal septum deviation and concha bullosa. A total of 80 patients who had minimal nasal septum deviation and concha bullosa at the middle turbinate were included in this study. Of these patients, 40 patients underwent middle turbinate lateral lamella resection, while 40 patients underwent middle turbinate lateral lamella resection plus septoplasty under general anesthesia. Complaints of nasal stuffiness in patients included were evaluated with the NOSE scale before the operation and three months after the operation. When preoperative and postoperative NOSE scale parameters were compared, all parameters statistically significantly improved postoperatively in both groups (p<0.05). The total NOSE scores were decreased significantly after surgery. Middle turbinate lateral lamella resection alone is as efficient as septoplasty plus middle turbinate lateral lamella resection for the treatment of symptomatic nasal stuffiness in selected patients.


Mutational activation of H-ras and K-ras genes is absent in N-nitroso-N-methylurea-induced liver tumors in rats.
We examined mutational activation of H- and K-ras genes in hyperplastic nodules and hepatocellular carcinomas induced by N-nitroso-N-methylurea or diethylnitrosamine using the polymerase chain reaction, followed by dot-blot hybridization. No mutational activation was detected in these hepatic lesions. The results indicate that low incidence of the activation of H- and K-ras genes in rat liver tumors is due to the organ specificity rather than the nature of the carcinogens used.


Schwann cell-specific Dp116 is expressed in glioblastoma cells, revealing two novel DMD gene splicing patterns.
The DMD gene is one of the largest human genes, being composed of 79 exons. Dystrophin Dp116 expressed from the promoter in intron 55 is a Schwann cell-specific isoform. The pathophysiological roles of Dp116 are largely unknown, because of its limited expression. This study assessed the expression of Dp116 in glioblastoma cells and evaluated the splicing patterns of the DMD gene in these cells. Full-length Dp116 cDNA was PCR amplified from U-251 glioblastoma cells. Dp116 protein was analyzed by Western blotting. Full-length Dp116 cDNA, extending from exon S1 to exon 79, was PCR amplified to avoid confusion with other DMD isoforms. The full-length Dp116 transcript was amplified as nearly 3 kb in size. Western blotting of U-251 cell lysates revealed a signal at a position corresponding to vector-expressed Dp116 protein, indicating that Dp116 is expressed in glioblastoma cells. Sequencing of the amplified product revealed five splice variants, all skipping exon 78. The most abundant transcript lacked only exon 78 (Dp116b), whereas the second most abundant transcript lacked both exons 71 and 78 (Dp116ab). A third transcript lacking exons 71-74 and 78 was also identified (Dp116bc). Two novel splicing patterns were also observed, one with a deletion of exons 68 and 69 (Dp116bΔ68-69) and the other with a 100 bp deletion in the 5' terminal end of exon 75 (75s), which was produced by the activation of a cryptic splice acceptor site (Dp116b75s). However, the splicing patterns in glioblastoma cells of DMD exons in Dp116 and Dp71 showed no significant differences. Dp116 is expressed in glioblastoma cells as five splicing variants, with Dp116b being the most abundant. Two novel splicing patterns of DMD exons were observed.


The effect of 1,25-dihydroxyvitamin D3 on the cytoskeleton of rat calvaria and rat osteosarcoma (ROS 17/2.8) osteoblastic cells.
1,25-dihydroxyvitamin D3 produces pronounced shape changes in fetal rat calvaria and osteosarcoma-derived (ROS 17/2.8) osteoblastic cells, characterized by retracting processes and cell rounding followed by aggregation of cells. The 1,25(OH)2D3 effect on ROS 17/2.8 morphology was determined morphometrically on scanning electron micrographs. The hormone effect was found to be dose dependent between 10(-12) and 10(-9) M. The shape changes appeared 12 h after hormone (10(-10) M) addition and were present in 80% of the ROS 17/2.8 cells and in 50% of the calvaria cells at 72 h. Cycloheximide at 1 microM, inhibited the hormone-dependent change in morphology. The 1,25(OH)2D3 effects were partially mimicked by 10(-8) M 25(OH)D3 but not by 10(-10) M 25(OH)D3 or 10(-11)-10(-8) M 24,25(OH)2D3. 1,25-dihydroxyvitamin D3 also increased cell proliferation twofold at 14 days in serum-free medium. 1,25(OH)2D3 treatment produced changes in microfilament organization, visualized with rhodamine-conjugated phalloidin. Microfilaments were localized at the terminal attachment points and in the perinuclear region, and few if any, were seen in the retracting processes themselves. Estimation of cytoskeletal actin and myosin by gel electrophoresis of Triton X-100 nonextractable proteins showed a 30% reduction in these proteins in the hormone-treated cells. Microtubules visualized by indirect immunofluorescence showed no major changes in organization. Both colchicine and cytochalasin D altered the hormone-induced shape change, suggesting that both microfilaments and microtubules were required for this process. Thus, 1,25(OH)2D3 had pronounced effects on cell shape in osteoblastic cells, probably via de novo protein synthesis. These changes lead to rearrangement of the cytoskeleton, primarily the microfilaments.


Engineering sensitivity and specificity of AraC-based biosensors responsive to triacetic acid lactone and orsellinic acid.
We previously described the design of triacetic acid lactone (TAL) biosensor 'AraC-TAL1', based on the AraC regulatory protein. Although useful as a tool to screen for enhanced TAL biosynthesis, this variant shows elevated background (leaky) expression, poor sensitivity and relaxed inducer specificity, including responsiveness to orsellinic acid (OA). More sensitive biosensors specific to either TAL or OA can aid in the study and engineering of polyketide synthases that produce these and similar compounds. In this work, we employed a TetA-based dual-selection to isolate new TAL-responsive AraC variants showing reduced background expression and improved TAL sensitivity. To improve TAL specificity, OA was included as a 'decoy' ligand during negative selection, resulting in the isolation of a TAL biosensor that is inhibited by OA. Finally, to engineer OA-specific AraC variants, the iterative protein redesign and optimization computational framework was employed, followed by 2 rounds of directed evolution, resulting in a biosensor with 24-fold improved OA/TAL specificity, relative to AraC-TAL1.


A Qualitative Study of Smoking-Related Causal Attributions and Risk Perceptions in Cervical Cancer Survivors.
The prevalence of smoking among cervical cancer survivors typically exceeds what is found among women in the general population and other cancer survivors. Yet, there is a dearth of literature on risk and protective factors related to smoking among cervical cancer survivors, especially when it comes to identification of variables that are amendable to intervention. To help fill this gap in the literature, this qualitative study examines the nature of smoking-related causal attributions and risk perceptions in cervical cancer survivors who smoked at cancer diagnosis. Participants are 21 female cervical cancer survivors (M=45.7, SD=8.4 years old), all diagnosed in the past five years. Nearly three-quarters of participants reported smoking in the past month. Smoking was not uniformly recognized as a cause of cervical cancer (whether in general or participants' own cancer); the link between smoking and lung, head-neck, and other cancers was more readily accepted. Despite generally weak endorsements of causal attributions, many participants reported smoking significantly increases risk for poor clinical (e.g., recurrence) and quality of life (e.g., pain) outcomes after cervical cancer diagnosis. Findings suggest cervical cancer survivors may not fully understand or appreciate the role of smoking in cervical cancer risk whereas their beliefs about the role of smoking in cervical cancer prognosis are more well-formed. This study highlights the potential role of causal attributions and risk perceptions in understanding and addressing the smoking-related experience of cervical cancer survivors.


Eradication of Helicobacter pylori infection induces an increase in body mass index.
The relationship between H. pylori infection and body mass indices is controversial. To investigate the relationship between H. pylori infection and body indices, and to examine the effect of H. pylori eradication therapy on body indices. Nine-hundred and thirty-two employees of an industrial corporation were examined for H. pylori infection and body mass indices. Three hundred and two H. pylori-positive cases diagnosed with chronic gastritis by upper gastrointestinal endoscopy or radiography underwent eradication therapy. Body mass indices, serum total cholesterol levels and symptom scores were obtained before and at 12 months after eradication therapy. There was no significant difference in body weight, body mass index (BMI) or serum total cholesterol level between the H. pylori-positive and H. pylori-negative groups. However, body weight and BMI increased significantly 12 months after eradication of H. pylori infection. In contrast, there was no significant difference in body weight and BMI 12 months after eradication therapy in the non-eradication group. Serum total cholesterol levels did not change after eradication therapy in either the eradication or non-eradication groups. Eradication of H. pylori infection induced an increase in BMI in industrial workers with chronic gastritis in Japan.


Genetic therapeutic advancements for Dravet Syndrome.
Dravet Syndrome is a genetic epileptic syndrome characterized by severe and intractable seizures associated with cognitive, motor, and behavioral impairments. The disease is also linked with increased mortality mainly due to sudden unexpected death in epilepsy. Over 80% of cases are due to a de novo mutation in one allele of the SCN1A gene, which encodes the α-subunit of the voltage-gated ion channel NaV1.1. Dravet Syndrome is usually refractory to antiepileptic drugs, which only alleviate seizures to a small extent. Viral, non-viral genetic therapy, and gene editing tools are rapidly enhancing and providing new platforms for more effective, alternative medicinal treatments for Dravet syndrome. These strategies include gene supplementation, CRISPR-mediated transcriptional activation, and the use of antisense oligonucleotides. In this review, we summarize our current knowledge of novel genetic therapies that are currently under development for Dravet syndrome.


Opioid and Drug Prevalence in Top 40's Music: A 30 Year Review.
Our objective was to identify current trends in the prose of popular music and, specifically, to identify if a relationship exists between the mention of opioid narcotics in Top 40's music and a rising prevalence of opioid use disorder in the United States. A list of Billboard's top 100 songs for each year of the past 30 years (1986 to 2016) was collected. Lyrics from the 40 most popular songs of each year were queried for reference to drugs and alcohol. χ2 analysis was used to identify statistically significant relationships with a level of significance set at P < .05. There was a statistically significant increase in the lyrical mention to opioids (0.0% to 5.0% of songs, P = .004), marijuana (0.6% to 17.2% of songs, P < .001), and alcohol (3.1% to 23.6% of songs, P < .001) in the 2010s decade when compared with the songs analyzed in the 1980s. The mention of opioid drugs and medications emerged in the late 1990s, and since, 57.1% of opioid-referencing songs mention prescription opioid medications and not heroin or street slang reference of the drug. Male- and female-driven mentions to drugs and alcohol have approached near equal rates in recent years. There is increasing prevalence in the lyrical mention of opioids, among other drugs, in Top 40's music. Nearly 50% of 2016 Top 40's songs reference drugs or alcohol. Further inquiry may be warranted to evaluate the societal impact and persuasive abilities of popular culture, including Top 40's music, on American drug and alcohol use.


The changes of intraoperative body temperature in adult liver transplantation: A retrospective study.
Body temperature is poorly regulated in patients with end-stage liver disease. Due to the prolonged surgery time and anhepatic time as well as the complex surgical procedures performed in liver transplantation, the body temperature fluctuates greatly. This study investigated the effect of intraoperative body temperature fluctuations on the prognosis of liver recipients. The body temperatures of liver recipients recorded from the induction of anesthesia (T0) until the end of surgery (T14) were retrieved. The patients were divided into two groups: the hypothermia group (< 35 °C and ≥ 5 min) and the normothermia group (≥ 35 °C or < 35 °C but < 5 min). Intraoperative and postoperative variables were compared between the two groups, and the correlations between the duration of hypothermia and the medical variables were analyzed. Of the 107 patients, 67 patients were in the normothermia group, and 40 in the hypothermia group. The lowest body temperature was at 5 min after reperfusion for the whole cohort. Compared with the normothermia group, patients in the hypothermia group were more prone to bleeding, had a longer intubation time and increased rates of bacterial infection and acute pulmonary edema after liver transplantation (P < 0.05). Hypothermia time was positively correlated with bleeding volume, intubation time, units of blood transfusions and intensive care stay, but negatively correlated with urine output. The intraoperative body temperature exhibited a graphical "V" trend, and the lowest temperature was at 5 min after reperfusion. The longer the duration of hypothermia, the more unfavourable the prognosis.


Megalencephaly: types, clinical syndromes, and management.
The differential diagnosis of megalencephaly poses a challenge to the clinician. The two major categories, metabolic and anatomic, include a number of conditions, many of them rare. This article provides a systematic approach to the patient with megalencephaly.


Pre-filled normal saline syringes to reduce totally implantable venous access device-associated bloodstream infection: a single institution pilot study.
Flushing totally implantable venous access devices (TIVADs) with manually filled saline syringes may increase contamination and catheter-related bloodstream infection (CRBSI). We used a retrospective cohort study to assess the impact of changing from manually filled syringes to manufactured pre-filled syringes on the frequency of CRBSI in 718 TIVADs. Manually filled syringes were used in 269 patients and pre-filled syringes in 449. The CRBSI rate was 2.7% in the pre-filled syringe group and 6.3% in the manually filled syringe group (P = 0.016). Sex, tumour type and stage, access site and access body side were not independent risk factors for CRBSI.


Catechol-O-methyltransferase rs4680 and rs4818 haplotype association with treatment response to olanzapine in patients with schizophrenia.
Antipsychotic drugs target primarily dopaminergic system which makes catechol-O-methyltransferase (COMT) an interesting target in studies searching for treatment response predictors in schizophrenia. The study assessed the association of the COMT rs4680 and rs4818 polymorphisms with therapeutic response to olanzapine, risperidone, clozapine or other antipsychotic medication after 8 weeks of monotherapy in patients with schizophrenia. 521 Caucasian patients with schizophrenia received a monotherapy with olanzapine (10-20 mg/day; N = 190), risperidone (3-6 mg/day; N = 99), or clozapine (100-500 mg/day; N = 102). The fourth group (N = 130) consisted of patients receiving haloperidol (3-15 mg/day), fluphenazine (4-25 mg/day) or quetiapine (50-800 mg/day). Treatment response was defined as a 50% reduction from the baseline positive and negative syndrome scale (PANSS) total and subscale scores, but also as an observed percentage reduction from the initial PANSS0-6 total and subscale scores. Carriers of the COMT rs4680 A allele and carriers of the COMT rs4680-rs4818 C-A haplotype block had greater reduction in the PANSS total scores following olanzapine treatment, compared to carriers of the COMT rs4680 GG genotype and other COMT rs4680-rs4818 haplotypes. The COMT rs4680 A allele, and COMT rs4680-rs4818 C-A haplotype, were significantly associated with therapeutic response in patients treated with olanzapine, but not in patients treated with other antipsychotics.


Chronoimmunohistochemical localization of epidermal growth factor in the submandibular gland of male rats.
Chronobiological oscillation was established for epidermal growth factor (r-EGF) in granular convoluted tubule (GCT) cells of the male rat submandibular gland (SMG) using immunohistochemistry. The high amplitude oscillation with a peak at 9 p.m. and low amplitude oscillation during the day time was noted. The distribution pattern of the r-EGF in the GCT segment was time-dependent, as it was seen at 3 p.m. when many cells with r-EGF staining were detectable. The higher reactivity during the activity phase of the rats may correlate with the intracellular biosynthesis of r-EGF required for cell proliferation and maintenance of ductal integrity. The chronobiological oscillation pattern of r-EGF seems to be important for the maintenance of ductal integrity and wound healing.


Arrhythmic complications of acute coronary syndromes.
Cardiac arrhythmias routinely manifest during or following an acute coronary syndrome (ACS). Although the incidence of arrhythmia is directly related to the type of ACS the patient is experiencing, the clinician needs to be cautious with all patients in these categories. As an example, nearly 90% of patients who experience acute myocardial infarction (AMI) develop some cardiac rhythm abnormality and 25% have a cardiac conduction disturbance within 24 hours of infarct onset. In this patient population, the incidence of serious arrhythmias, such as ventricular fibrillation (4.5%) ,is greatest in the first hour of an AMI and declines rapidly thereafter. This article addresses the identification and treatment of arrhythmias and conduction disturbances that complicate the course of patients who have ACS, particularly AMI and thrombolysis. Emphasis is placed on mechanisms and therapeutic strategies.


Sitagliptin increases tau phosphorylation in the hippocampus of rats with type 2 diabetes and in primary neuron cultures.
Increasing evidence supports an association between Alzheimer's disease (AD) and diabetes. In this context, anti-diabetic agents such as rosiglitazone and glucagon-like peptide (GLP)-1 have been reported to reduce pathologies associated with AD, including tau hyperphosphorylation, suggesting that such agents might be used to treat AD. One such anti-diabetic agent is sitagliptin, which acts through inhibition of dipeptidyl peptidase (DPP)-IV to increase GLP-1 levels. Given this action, sitagliptin would be predicted to reduce AD pathology. Accordingly, we investigated whether sitagliptin is effective in attenuating AD pathologies, focusing on tau phosphorylation in the OLETF type 2 diabetic rat model. Unexpectedly, we found that sitagliptin was not effective against pathological tau phosphorylation in the hippocampus of OLETF type 2 diabetes rats, and instead aggravated it. This paradoxically increased tau phosphorylation was attributed to activation of the tau kinase, GSK3β (glycogen synthase kinase 3β). Sitagliptin also increased ser-616 phosphorylation of the insulin receptor substrate (IRS)-1, suggesting increased insulin resistance in the brain. These phenomena were recapitulated in primary rat cortical neurons treated with sitagliptin, further confirming sitagliptin's effects on AD-related pathologies in neurons. These results highlight the need for caution in considering the use of sitagliptin in AD therapy.


Newborn screening for lysosomal diseases: current status and potential interface with population medical genetics in Latin America.
The aim of newborn screening (NBS) programs is to detect a condition in a presymptomatic baby and provide management measures which could significantly improve the natural history of the disease. NBS programs for metabolic diseases were first introduced in North America and Europe and in the 1960s for phenylketonuria, expanded a few years later to include congenital hypothyroidism, and have been growing steadily in terms of number of conditions tested for and number of countries and births covered. Lysosomal storage diseases (LSDs) are a group of around 50 genetic conditions in which a defect in a lysosomal function occurs. LSDs are progressive conditions, being usually asymptomatic at birth, but with clinical features becoming apparent in childhood, with severe manifestations in most instances, high morbidity and shortened life span. Although individually rare, the prevalence of LSDs is significant when the group is considered as a whole (around 1:4,000-1:9,000 live births). Several management techniques, including bone marrow transplantation, enzyme replacement therapy, substrate inhibition therapy, pharmacological chaperones and many other approaches are transforming the LSDs into treatable conditions. However, lack of awareness and lack of access to tests cause a significant delay between onset of symptoms and diagnosis. Several lines of evidence showing that the earlier introduction of therapy may provide a better outcome, are bringing support to the idea of including LSDs in NBS programs. Due to advances in technology, high-throughput multiplex methods are now available for mass screening of several LSDs. Pilot projects were already developed in many countries for some LSDs, with interesting results. Although some NBS in Latin America has been carried out since the 1970s, it has so far been incorporated as a public health program in only a few countries in the region. It will probably take many years before NBS is implemented in most Latin American countries with a comprehensive coverage in terms of number of diseases and number of births. Population medical genetics is the area of medical genetics that aims at the study and medical care of the population, and not of the family, which is the case for clinical or medical genetics itself. It combines different aspects of genetics: clinical genetics; human population genetics, which investigates populations according to micro-evolutionary parameters; epidemiological genetics, traditionally involved in the study of common chronic diseases of polygenic etiology, except for Mendelian diseases; and sanitary or community genetics, which stands at the interface with public health, giving support to preventive health measures. Taking into account that several LSDs were identified in a higher frequency in selected areas and/or populations, the population medical genetics approach could help to introduce the NBS for LSDs in the region, with identification of areas with higher risk for selected diseases and design of customized screening program to address specific needs. As an example of the potential of this approach, a pilot program of NBS for MPS VI was implemented in a community from North East Brazil where 13 cases of MPS VI were identified in an area with 50,000 inhabitants. This program, which will enable not only identification and early treatment of affected newborns but also carrier detection, and which would allow genetic counseling for at-risk couples, could be an alternative model for a customized NBS of LSDs to be carried out in selected regions.


The role of calcium in the conformational dynamics and thermal stability of the D-galactose/D-glucose-binding protein from Escherichia coli.
We have characterized stability and conformational dynamics of the calcium depleted D-galactose/D-glucose-binding protein (GGBP) from Escherichia coli. The structural stability of the protein was investigated by steady state and time resolved fluorescence, and far-UV circular dichroism in the temperature range from 20 degrees C to 70 degrees C. We have found that the absence of the Ca(2+) ion results in a significant destabilization of the C-terminal domain of the protein. In particular, the melting temperature decreases by about 10 degrees C with the simultaneous loss of the melting cooperativity. Time resolved fluorescence quenching revealed significant loosening of the protein when highly shielded Trp residue(s) became accessible to acrylamide at higher temperatures. We have documented a significant stabilizing effect of glucose that mostly reverts the effect of calcium, that is, the thermal stability of the protein increases by about 10 degrees C and the melting cooperativity is restored. Moreover, the protein structure remains compact with low amplitude of the segmental mobility up to high temperatures. We have used molecular dynamics to identify the structural feature responsible for changes in the temperature stability. Disintegration of the Ca(2+)-binding loop seems to be responsible for the loss of the stability in the absence of calcium. The new insights on the structural properties and temperature stability of the calcium depleted GGBP contribute to better understanding of the protein function and constitute important information for the development of new biotechnological applications of this class of proteins.


Inactivation of particle-associated viral surrogates by ultraviolet light.
This study investigated whether colloid-sized particles can enmesh and protect viruses from 254-nm ultraviolet (UV) light and sought to determine the particle characteristics (e.g. size, chemical composition) that are most relevant in causing a protective effect. Two viral surrogates (MS2 coliphage and bacteriophage T4), three types of particles (kaolin clay, humic acid powder, and activated sludge), two coagulants (alum and ferric chloride), two filtration conditions (none and 0.45 microm), and two UV doses (40 and 80 mJ/cm2 for MS2 coliphage; 2 and 7 mJ/cm2 for bacteriophage T4) were considered in a series of bench-scale UV collimated beam experiments. Transmission electron microscopy was used to qualitatively confirm the phage particle-association after coagulation. Humic acid and activated sludge floc particles shielded both viral surrogates to a statistically significant degree (with >99% confidence) relative to particle-free control conditions, while the kaolin clay particles provided no significant protection. The results of the study suggest that particles <2 microm in diameter are large enough to protect viruses from UV light and that particulate chemical composition (e.g. UV-absorbing organic content) may be a critical factor in the survival of particle-associated viruses during UV disinfection.


Radiographic signs of excessive occlusal forces are associated with marginal bone loss: a retrospective clinical study.
Work in animal models has implicated excessive occlusal forces and occlusal trauma as co-destructive factors for periodontitis. The main aim of the present study was to make a radiographic assessment of the effects of excessive occlusal forces, ie occlusal/incisal tooth wear, widening of the periodontal space, and the presence of a mandibular torus, on interproximal marginal bone loss in a large series of patients. A secondary aim was to evaluate the statistical correlation between the parameters in two specific teeth and those of 12 teeth for marginal bone loss and six teeth for occlusal/incisal tooth wear within the same individual. A total of 1,950 full-mouth radiographic surveys were analyzed retrospectively. Interproximal marginal bone loss was quantified relative to the root length (Schei ruler technique). In addition, occlusal/incisal tooth wear and periodontal ligament space widening of the periodontal space were assessed, as well as the presence of a mandibular torus. Odds ratio and logistic regression analysis were used to determine the association between occlusal trauma and marginal bone loss. The correlation of the measured parameters between the values for specific teeth and the whole dentition was evaluated from data from the first 400 radiographs. Teeth 41 and 33 showed the best correlation to the whole dentition: 0.85 for interproximal marginal bone loss, 0.83 for widening of the periodontal space, and 0.97 for occlusal/incisal tooth wear. The results of a logistic regression analysis with age as an independent variable, revealed a significant association between bone loss and both tooth wear (odds ratio = 2.767) and bone loss and widening of the periodontal space (odds ratio = 2.585). Tooth wear was positively correlated to both widening of the periodontal space and marginal bone loss. No correlation was found between the presence of a mandibular torus and marginal bone loss.


Effects of calcitonin gene-related peptide on apoptosis of peripheral blood mononuclear cells from patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease with abnormal apoptosis and autoantibody production. Calcitonin gene-related peptide (CGRP) is a neuropeptide produced by the central and peripheral nervous systems and by endocrine cells. It can influence cell death in thymocytes and cultured smooth muscle cells, and inhibits the production of interleukin (IL)-2, which inhibits apoptosis. To investigate the effects of calcitonin gene-related peptide (CGRP) on apoptosis of peripheral blood mononuclear cells (PBMCs) from patients with SLE. The percentage of apoptosis of PBMCs from patients with SLE and healthy blood donors were examined using annexin-V/propidine iodide staining 48 h after culturing with CGRP and/or its receptor antagonist CGRP(8-37) at various concentrations. IL-2 activity in culture supernatants was determined using the incorporation of 3H-TdR by the IL-2-dependent cell line CTLL and evaluated by ELISA. The percentage of spontaneous apoptosis of PBMCs from patients with SLE was higher than that of healthy blood donors (34.18 +/- 2.86 vs. 18.23 +/- 0.81, P < 0.001). CGRP, at all tested concentrations, had no effect on apoptosis of PBMCs from healthy blood donors, but significantly inhibited apoptosis of PBMCs from patients with SLE at concentrations of >or= 0.5 x 10(-8) mol/L (0.5 x 10(-8) mol/L: 32.01 +/- 3.98 vs. 34.18 +/- 2.86, P < 0.05; 1.0 x 0(-8) mol/L: 26.76 +/- 2.69 vs. 34.18 +/- 2.86, P < 0.001; 1.5 x 10(-8) mol/L: 25.97 +/- 2.65 vs. 34.18 +/- 2.86, P < 0.001), and the effect plateaued at 1.0 x 10(-8) mol/L, at which level inhibition was not significantly increased with increasing concentration. However, CGRP, at any concentration tested, could not reduce the rate of apoptosis of PBMCs from patients with SLE to the normal range. There were significant positive relationships between the effect of CGRP, on apoptosis of PBMCs and SLE Disease Activity Index (0.5 x 10(-8) mol/L: r(s) = 0.328, P < 0.05; 1.0 x 10(-8) mol/L: r(s) = 0.431, P < 0.01; 1.5 x 10(-8) mol/L: r(s) = 0.419, P < 0.01). CGRP(8-37) itself had no effect on apoptosis, but was able to block the effects of CGRP on PBMCs (0.5 x 10(-8) mol/L: 32.01 +/- 3.98 vs. 33.12 +/- 2.37, P < 0.05; 1.0 x 10(-8) mol/L: 26.76 +/- 2.69 vs. 34.73 +/- 2.32, P < 0.001; 1.5 x 10(-8) mol/L: 25.97 +/- 2.65 vs. 35.25 +/- 3.37, P < 0.001). There was no effect of CGRP on IL-2 production. These results indicate that CGRP plays an important role in the apoptosis of PBMCs from patients with SLE via its receptor; low plasma levels of CGRP may cause accelerated apoptosis. This regulation does not seem to be related to IL-2.


Prediction of response to neoadjuvant chemotherapy in breast cancer patients by circulating apoptotic biomarkers nucleosomes, DNAse, cytokeratin-18 fragments and survivin.
Biomarkers predicting response to neoadjuvant chemotherapy in locally confined breast cancer (LBC) are highly needed. We prospectively assessed serial blood levels of apoptotic biomarkers nucleosomes, DNAse activity, cytokeratin-18 fragments (M30) and survivin in 51 LBC patients and correlated them with response to neoadjuvant treatment and established tumor markers. As controls, we used 31 healthy subjects, 13 patients with benign diseases and 28 with metastatic breast cancer (MBC). Levels of nucleosomes and survivin were elevated in LBC and MBC while M30, CEA and CA 15-3 levels were only elevated in MBC. During neoadjuvant chemotherapy, LBC patients with no change of disease (N=13) had significantly higher pretherapeutic levels of nucleosomes than patients with remission (N=38). We conclude that apoptotic biomarkers bear valuable information for diagnosis and therapy response prediction in LBC patients.