Anatomical and Procedural Factors of Severe Pulmonary Vein Stenosis After Cryoballoon Pulmonary Vein Ablation.
This study examined the anatomical or procedural factors associated with severe pulmonary vein (PV) stenosis after cryoballoon PV isolation. PV stenosis is a complication associated with cryoballoon ablation. The study included 170 consecutive patients with paroxysmal atrial fibrillation who underwent cryoballoon ablation. In addition to factors generally considered to be related to the occurrence of PV stenosis (PV size, cryoballoon application number and time, and minimum freezing temperature), we evaluated the following 4 factors: 1) depth of balloon position; 2) the PV angle (internal angle between each PV and horizontal line); 3) noncoaxial balloon placement (hemispherical occlusion); and 4) contact surface area between the cryoballoon and the PV wall (defined as the balloon contact ratio). Severe PV stenosis (≥75% area reduction) was observed in 9 (1.3%) PVs (6 left superior and 3 right superior PVs) in 9 patients. The PV size, cryoballoon application number and time, minimum freezing temperature, and the depth of cryoballoon position were not significantly associated with occurrence of severe PV stenosis, but the PV angle was significantly smaller in PVs with severe stenosis than it was in those without stenosis (25.6 ± 9.7° vs. 34.2 ± 6.4°; p < 0.001). Hemispherical occlusion was more frequently observed and balloon contact ratio was larger in PVs with severe stenosis (55.6% vs. 14.8%; p = 0.049) than in those without stenosis (0.70 ± 0.06 vs. 0.54 ± 0.08; p < 0.001). A horizontally connecting PV, noncoaxial placement of cryoballoon, and a larger contact surface area of the cryoballoon were predictors of the occurrence of severe PV stenosis after cryoballoon ablation.


Endoscopic Management of Spontaneous Clival Cerebrospinal Fluid Leaks: Case Series and Literature Review.
Spontaneous cerebrospinal fluid leaks are most commonly located along the anterior skull base. Sphenoidal localization is less common, and clival localization is even rarer. We analyzed a group of patients with spontaneous leaks and selected patients with clival localization. This article discusses surgical management of these entities and provides a brief literature review regarding spontaneous clival leaks. Of a cohort of 67 patients who presented to our departments with a spontaneous leak during the period 2005-2014, a retrospective data analysis was performed on 6 patients with clival localization of the defect. A skull base repair with a multilayered reconstruction was performed in 3 patients, and a single-layered reconstruction using a pedicled nasoseptal flap was performed in 3 patients. The patients included 6 women with a mean age of 60 years (range, 36-91 years). The mean length of the follow-up period was 69.5 months (range, 22-114 months). The overall success rate of the primary endoscopic repair was 83.3% (5 of 6 patients); this increased to 100% after revision surgery. This series, although numerically limited, suggests that a minimally invasive endoscopic repair of idiopathic clival leaks may be accomplished with an acceptable rate of morbidity and excellent outcomes. Moreover, the pedicled nasoseptal flap has been confirmed to be the "workhorse" for the reconstruction of clival defects.


Diversity and dynamics of microbial communities during spontaneous fermentation of Cabernet Sauvignon (Vitis vinifera L.) from different regions of China and their relationship with the volatile components in the wine.
Wine presents the most distinct geographic signatures among all agricultural products, and these geographic characteristics of the wine are enhanced by the actions of indigenous microorganisms. China is one of the largest wine-producing and consuming nations in the world. The wine-related microbial resources are abundant in China, although their geographic distribution patterns and their contribution to the aroma of wine remain to be elucidated. In the present study, Cabernet Sauvignon samples from four wine-producing regions in China were subjected to high-throughput sequencing and HS-SPME-GC-MS techniques to study the diversity and dynamics of the microorganisms that were present during the spontaneous fermentation process and to provide a preliminary understanding of the contribution of these microorganisms to the volatile components of the wine. The results revealed significant differences in the microbial diversity in the grape musts among different vineyards, which led to significant differences in the composition of the volatile metabolites of the produced wine. Moreover, while the fermentation process was observed to have reshaped the structure of the microbial community, specific characteristics of the vineyard were retained at the completion of the fermentation process. The associations between microbiota diversity and wine chemicals suggested that the dominant species during the fermentation process largely determined the volatile components of the wine. The present study enhances the understanding of Chinese wine terroir and provides a scientific basis for maintaining the regional microbial biodiversity to sustain viticulture and winemaking.


EROD activity, serum SDH and PAH biliary metabolites in sand flathead (Platycephalus bassensis) collected in Port Phillip Bay, Australia.
In order to evaluate the health status of fish inhabiting Port Phillip Bay, Australia, southern sand flathead (Platycephalus hassensis, N = 133) were collected at six stations throughout the Bay. Fish had a similar serum sorbitol dehydrogenase (SDH) activity level (p = 0.12), indicating that they were not experiencing hepatocellular injuries. Ethoxyresorufin-O-deethylase (EROD) activity was generally lower in the non-urbanized and non-industrialized southern part of the Bay. The highest EROD activity was observed in Hobson Bay, the closest station from Melbourne city. Naphthalene-type biliary metabolites were also highest in Hobson Bay with intermediate levels found in Corio Bay where refineries are present. An opposite trend was observed with the pyrene-type bile metabolites, the highest levels being observed in Corio Bay while intermediate levels were found in Hobson Bay. The ratio of naphthalene-type to benzo(a)pyrene (B(a)P)-type metabolites indicate that relatively to other sites sampled in Port Phillip Bay, Corio Bay is subjected to enriched petroleum hydrocarbons of pyrolytic origin. Temporal trends indicate that the availability of xenobiotics to fish remained unchanged over the 1990s.


Central glucoregulation in the pigeon Columba livia. Effects of intraventricular injections of carbachol and catecholamines on blood glucose concentration.
The effect of chemical stimulation of the central nervous system on glucoregulation was studied in pigeons (Columba livia). Adrenaline (30 nmol), noradrenaline (30 or 80 nmol) and carbachol (27 nmol) were injected in 1 microliter NaCl directly into the lateral ventricle and changes in blood glucose concentration were measured. The intraventricular injection of adrenaline resulted in rapid hyperglycemia, whereas the injection of either carbachol or noradrenaline into the lateral ventricle did not cause any significant changes in blood glucose concentration. These results suggest that adrenaline-containing neurons may be involved in central mechanisms controlling blood glucose concentration in the pigeon.


HIV-related bronchiectasis in children: an emerging spectre in high tuberculosis burden areas.
Human immunodeficiency virus (HIV) infected children have an eleven-fold risk of acute lower respiratory tract infection. This places HIV-infected children at risk of airway destruction and bronchiectasis. To study predisposing factors for the development of bronchiectasis in a developing world setting. Children with HIV-related bronchiectasis aged 6-14 years were enrolled. Data were collected on demographics, induced sputum for tuberculosis, respiratory viruses (respiratory syncytial virus), influenza A and B, parainfluenza 1-3, adenovirus and cytomegalovirus), bacteriology and cytokines. Spirometry was performed. Blood samples were obtained for HIV staging, immunoglobulins, immunoCAP®-specific immunoglobulin E (IgE) for common foods and aeroallergens and cytokines. In all, 35 patients were enrolled in the study. Of 161 sputum samples, the predominant organisms cultured were Haemophilus influenzae and parainfluenzae (49%). The median forced expiratory volume in 1 second of all patients was 53%. Interleukin-8 was the predominant cytokine in sputum and serum. The median IgE level was 770 kU/l; however, this did not seem to be related to atopy; 36% were exposed to environmental tobacco smoke, with no correlation between exposure and CD4 count. Children with HIV-related bronchiectasis are diagnosed after the age of 6 years and suffer significant morbidity. Immune stimulation mechanisms in these children are intact despite the level of immunosuppression.


ON SPECIES and OTHER TAXA.
Abstract- It is argued that taxa, whether Linnaean or phylogenetic, belong to Popper's worlds 2 and 3, the worlds of knowledge, but that they represent entities residing in world 1, the world of objects, namely, classes of living beings. The Linnaean taxa are concepts, and thus untestable, whereas phylogenetic taxa are statements, the monophyletic taxa being true, and the paraphyletic and polyphyletic ones false statements. The taxa are neither strictly nor numerically universal statements, but probabilistic ones which cannot be falsified by single observations. It is suggested that the classical "species problem" is due to the fact that "species" has been used in three different senses. First, traditionally it has been assumed that the specific "essence" of an organism is that by which it is what it is. When we know the species, we know the organism. Second, the species are terminal taxa in the phylogenetic hierarchy. This implies that it is only a very small part of the "essence" of the organism which distinguishes the species. The remaining part characterizes the succession of superior taxa in the phylogenetic lineage which ends with the species in question. Third, the species has been regarded to be the "evolutionary unit." This idea may be refuted for two reasons: (1) since concepts and statements cannot evolve, species cannot evolve either, and (2) it is generally in very small isolated populations that evolutionary innovations are first established. In Linnean systematics the superior taxa are allotted categorical rank. The fact that the classification is constrained by this conventional stipulation implies that the superior taxa are often man-made artifacts. In the phylogenetic hierarchy, composed of monophyletic taxa, the ontological states of the taxa is completely independent of their numerical rank; the kingdom is as "real" as the species.


Clinical prediction of response to lithium prophylaxis in bipolar patients: the importance of the previous pattern of course of the illness.
The response to lithium prophylaxis was evaluated in a sample of bipolar patients subdivided into groups, according to the previous pattern of course for their illness: MDI (sequence mania-depression-free interval), DMI (sequence depression-mania-free interval), CC-LC (continuous circular course with long cycles), CC-RC (continuous circular course with rapid cycles), IRR (irregular course). The percentage of responders to treatment was significantly different among the five groups, and the difference could be ascribed mainly to the high response rate in the MDI group and the low response rate in the DMI and CC-RC groups. These data suggest that the classification of bipolar patients on the basis of the previous pattern of their course of illness may be useful for predicting lithium response.


Posttetanic potentiation of primary response and late negative wave in the somatosensory region of the cortex of the cat.
The experiments were carried out on cats under nembutal anesthesia. Stimulation of the ventroposterolateral nucleus of the thalamus or the white matter by a single stimulus elicited a primary response in the middle layers of the somatosensory cortex, and after it, a late negative wave, the duration of which reaches 40-70 msec. This potential does not have dipole reflection on the surface of the cortex and is apparently generated primarily by stellate cells. As a result of the tetanization of the ventroposterolateral nucleus or the white matter, a sharp increase in the amplitude of the late negative wave is observed, i.e., its posttetanic potentiation, while the primary response changes to a significantly lesser degree. Posttetanic potentiation is observed for 2-2.5 h. Posttetanic potentiation of the late negative wave is probably governed by processes occurring at the level of the middle layers of the cerebral cortex.


Prospective Observational Study Evaluating the Prognostic Value of the G8 Screening Tool for Extensive-Stage Small Cell Lung Cancer Patients Who Received Programmed Death-Ligand 1 Inhibitor plus Platinum-Etoposide Chemotherapy.
Programmed death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy is used as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), regardless of age. We examined the role of the Geriatric 8 (G8) screening tool for evaluating treatment outcomes in patients with ES-SCLC treated with PD-L1 inhibitor plus platinum-etoposide chemotherapy as first-line therapy. Between September 2019 and October 2021, we prospectively evaluated patients with ES-SCLC treated with immunochemotherapy at ten institutions in Japan. The G8 score was assessed before treatment initiation. We evaluated 44 patients with ES-SCLC. Patients with G8 score > 11 had longer overall survival (OS) than those with G8 score ≤ 11 (not reached versus 8.3 months; log-rank test, p = 0.005). In univariate and multivariate analyses, G8 score > 11 [hazard ratio (HR) 0.34; 95% confidence interval (CI) 0.15-0.75; p = 0.008 and HR 0.34; 95% CI 0.14-0.82; p = 0.02, respectively) and performance status (PS) of 2 (HR 5.42; 95% CI 2.08-14.2; p < 0.001 and HR 6.94; 95% CI 2.25-21.4; p < 0.001, respectively) were independent prognostic factors for OS. Among patients with good PS (0 or 1), the OS in patients with G8 score > 11 was significantly longer than that in patients with G8 score ≤ 11 (not reached versus 12.3 months; log-rank test, p = 0.02). G8 score evaluation before treatment initiation was useful as a prognostic factor for ES-SCLC patients who received PD-L1 inhibitors and platinum-etoposide chemotherapy, even with good PS.


Draft Genome Sequence of Vibrio parahaemolyticus Strain PH1339, Which Causes Acute Hepatopancreatic Necrosis Disease in Shrimp in the Philippines.
We report the first draft genome sequence of an acute hepatopancreatic necrosis disease (AHPND)-causing Vibrio parahaemolyticus strain isolated from a Penaeus vannamei sample from the Philippines. The strain carries the genes encoding the Pir-like toxin pair PirAvp and PirBvp.


Long-term outcome of allogeneic PBSC transplantation in pediatric patients with hematological malignancies: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) and the Spanish Group for Allogeneic Peripheral Blood Transplantation (GETH).
We analyzed the clinical outcome in 90 children undergoing allogeneic PBSC transplantation from HLA-identical relative for leukemia. GvHD prophylaxis was CsA+ methotrexate in 50 and CsA+/-steroids in 40. Median CD34+ cells infused were 6 x 10(6)/kg (range, 1.4-32). Median follow-up was 60 months (range, 6-115). CI of transplant-related mortality (TRM) was 18.4+/-4%. On multivariate analysis, high Lansky score (>80) at transplantation was associated with lower TRM (HR, 0.9; P<0.0002). Relapse incidence (RI) was 33.6+/-6%. On multivariate analysis, high Lansky score at transplantation and cGvHD were associated with lower RI (HR, 0.04; P<0.0005 and HR, 0.23; P<0.03, respectively). Disease-free survival (DFS) was 57.8+/-5%. Disease status at transplantation (HR, 0.33; P<0.02), steroid treatment at day +90 (HR, 5.61; P<0.005) and cGvHD (HR, 0.23; P<0.005) had a significant impact on DFS in multivariate analysis. CI of cGvHD was 63.7+/-7%. Patients with cGvHD had better DFS (65+/-5%) because of lower RI (15.7+/-6%) and similar TRM (27.4+/-4%). These data suggest acceptable long-term outcomes after allogeneic PBSC transplantation in children despite the high incidence of cGvHD. These patients had a lower risk of relapse and a better DFS.


Clinical evaluation of removable partial denture rest seat adaptation.
The clinical relationship between the removable partial denture cast occlusal rest and the corresponding rest seat was examined. Under the conditions of the study, it was found that rests of mandibular Class I and II removable partial dentures fit significantly better than those of mandibular Class III and IV prostheses. No significant difference was noted between similar types of maxillary removable partial dentures in this regard. In evaluating the fit of specific portions of the occlusal rest, it was found that the marginal ridge zone was more closely adapted to the rest seat than other zones for all types of removable partial dentures. However, contact, as defined in this analysis, was found to exist on a random basis in all four quadrants of the occlusal rests evaluated. In spite of this fact, one fifth of the occlusal rests did not contact the opposing rest seat at any point. Improved fit with length of service was not substantiated by a cross-sectional analysis. Suggestions were made to assist the clinician in achieving a better fit between the framework and dentition in removable partial dentures.


Drinking and haemodynamic changes induced in the dog by intracranial injection of components of the renin-angiotensin system.
1. Intracranial injections of the individual components of the renin-angiotensin system caused drinking in water-replete dogs. 2. Angiotensin II was the most reliable, potent and rapidly acting intracranial dipsogen and elicited drinking in the absence of peripheral circulatory changes. After the highest dose of angiotensin II (10(-9) mole) five dogs drank a mean amount of 380.0 +/- 88.6 ml. For the other components, the order of dipsogenic effectiveness was angiotensin I, synthetic renin substrate, and angiotensin III. 3. Isotonic saline, bradykinin (10(-10) mole), eledosin-hexapeptide (10(-10) mole), oxytocin (10(-10) mole) and prostaglandin F2alpha (1-200 X 10(-12) mole) were ineffective. 4. Intracranial renin (10 m-u.) produced a mean intake of 445 +/- 152 ml. of water in eight dogs. 5. Dog renin substrate and synthetic renin substrate, injected intracranially in a dose of 10(-10) mole, produced similar intakes of water but these amounts were very much less than the volume drunk in response to the same dose of angiotensin II. 6. None of the components injected into dipsogenically responsive sites in the brain caused changes in blood pressure, although the act of drinking itself produced a small rise. 7. Angiotensin II at the highest dose produced drinking when injected into the subfornical organ, preoptic region, anterior hypothalamus, lateral ventricle, third ventricle, ventral hippocampus and mid-line thalamus. Negative sites were found in the caudate nucleus, fourth ventricle, mid-brain, posterior thalamus, dorsal hippocampus, lateral hypothalamus and posterior hypothalamus. 8. After the lowest dose of intracranial angiotensin II (10(-12) mole) only the preoptic region and subfornical orgal were responsive. These two sites were equally sensitive in terms of latency and amounts drunk at all doses injected. 9. Angiotensin did not necessarily have to reach a cerebral ventricle in order to cause drinking. 10. The dog resembles the rat in its responsiveness to the dipsogenic action of intracranial angiotensin II. The regions of the brain from which drinking can be elicited are more widespread than has been claimed by some in the rat.


The effects of endothelium-dependent vasodilators on cardiac output and their distribution in the anaesthetized rat: a comparison with sodium nitroprusside.
1. The effects of sodium nitroprusside, acetylcholine and bradykinin on cardiac output and its distribution were studied in the anaesthetized, vagotomised rat preparation by use of 113Sn-labelled microspheres. 2. All three vasodilators lowered peripheral arterial blood pressure, but only bradykinin significantly reduced total peripheral resistance without reducing cardiac output. Bradykinin caused tachycardia, but this was offset by a reduction in stroke volume. These effects of bradykinin were not altered by indomethacin (4 mg kg-1). Acetylcholine and sodium nitroprusside both caused significant (P less than 0.05) reductions in stroke volume and cardiac output. 3. Bradykinin reduced vascular resistance in the liver, stomach, small intestine, large intestine, pancreas/mesentery, epididimides, skeletal muscle and fat. These responses were not affected by indomethacin, whereas, the reduction in vascular resistance in the brain induced by bradykinin was abolished by indomethacin. 4. Acetylcholine caused a reduction in renal vascular resistance, where bradykinin had no effect. However, acetylcholine did not cause any haemodynamic changes in the bradykinin-sensitive intestinal vasculature. 5. Acetylcholine caused vasoconstriction in the coronary and epididymal vasculature. Bradykinin in the presence of indomethacin induced vasoconstriction in the skin. 6. In conclusion, the data show that, with the possible exception of the brain and the skin, the vasodilator actions of bradykinin can adequately be transduced (presumably by endothelium-derived relaxing factor, EDRF) in the absence of prostacyclin synthesis. Additionally, these results indicate that the vasculature of the stomach, pancreas/mesentery, epididimides and skeletal muscle are equally sensitive to both acetylcholine and bradykinin, whereas the kidneys showed selectivity towards acetylcholine and the intestines towards bradykinin. These results may indicate differential receptor populations.


The basis and design for time-restricted eating compared with daily calorie restriction for weight loss and colorectal cancer risk reduction trial (TRE-CRC trial).
Approximately 42% of American adults are living with obesity, increasing their risk of colorectal cancer (CRC). Efficacious approaches to prevent and treat obesity may reduce CRC incidence. Daily calorie restriction (Cal-R) is the most common approach to treating obesity, yet clinically meaningful weight loss is elusive owing to waning adherence. Time-restricted eating (TRE) consists of consuming foods within a specified time frame, creating a natural calorie deficit. TRE in animals shows cancer protective effects. In humans, TRE is safe and acceptable among adults with obesity, producing ~3% to 5% weight loss and reductions in oxidative stress and insulin resistance. However, TRE has not been tested rigorously for CRC preventive effects. The authors describe a 12-month randomized controlled trial of 8-hour TRE (ad libitum 12 PM-8 PM), Cal-R (25% restriction daily), or Control among 255 adults at increased risk for CRC and with obesity. Effects on the following will be examined: 1) body weight, body composition, and adherence; 2) circulating metabolic, inflammation, and oxidative stress biomarkers; 3) colonic mucosal gene expression profiles and tissue microenvironment; and 4) maintenance of benefits on body weight/composition and CRC risk markers. This study will examine efficacious lifestyle strategies to treat obesity and reduce CRC risk among individuals with obesity.


[Isotopic renogram after captopril administration: clinical experience in the assessment of the hypertensive patient].
Isotopic renogram allows renal function to be estimated in both kidneys independently. The glomerular filtrate in ischemic kidneys is largely dependent on the tone of the efferent glomerular arteriolae and therefore on the concentration of circulating angiotensin II. In 42 patients with severe high blood pressure in whom renal angiographic study was carried out for suspicion of vasculo-renal hypertension, an isotopic renogram using 99m Tc-DTPA as a tracer was performed in basal conditions and following the administration of 50 mg of oral captopril. In 21 patients both the angiographic examination and the post-captopril renogram were normal. In 16 patients in whom uni or bilateral stenosis higher than 50% of the lumen of renal artery was observed on angiographic examination, the post-captopril renogram showed changes. In 5 patients the angiography was normal while the renogram showed evaluable changes. No false negatives were observed in the post-captopril renogram, however the basal renogram was not demonstrative in 6 patients with stenosis of the renal artery. Sensitivity of the test was thus 100% and specificity 80%. The positive predictive value was 76% and the negative predictive value 100%. The post-captopril renogram may be a useful test in the functional study of renal behaviour in patients with vasculo-renal hypertension.


Chitosan-based transparent and conductive hydrogel with highly stretchable, adhesive and self-healing as skin-like sensor.
Hydrogel sensors attained increasing attention due to their excellent mechanical and sensing properties. However, it is still a big challenge to fabricate hydrogel sensors with multifunctional properties of transparent, high stretchability, self-adhesive and self-healing ability. In this study, chitosan as a natural polymer has been employed to construct a polyacrylamide-chitosan-Al3+ (PAM-CS-Al3+) double network (DN) hydrogel with high transparency (>90 % at 800 nm), good electrical conductivity (up to 5.01 S/m) and excellent mechanical properties (strain and toughness as high as 1040 % and 730 kJ/m3). Moreover, the dynamic ionic and hydrogen bond interaction between PAM and CS endowed the PAM-CS-Al3+ hydrogel good self-healing ability. In addition, the hydrogel possesses good self-adhesive ability on different substrates, including glass, wood, metal, plastic, paper, polytetrafluoroethylene (PTFE) and rubber. Most importantly, the prepared hydrogel could be assembled into transparent, flexible, self-adhesive, self-healing and high sensitive strain/pressure sensor for monitoring human body movement. This work may pave the way for fabricating the multifunctional chitosan-based hydrogels which has potential application in the fields of wearable sensor and soft electronic devices.


Cell-permeable ceramides inhibit the stimulation of DNA synthesis and phospholipase D activity by phosphatidate and lysophosphatidate in rat fibroblasts.
The interactions of ceramides with phosphatidate and lysophosphatidate in the regulation of signal transduction in rat fibroblasts were examined. C2- and C6-ceramides (N-acetylsphingosine and N-hexanoylsphingosine, respectively) at 10 microM inhibited the stimulation of DNA synthesis that was produced by 50-100 microM phosphatidate, or lysophosphatidate, or by exogenous phospholipase D. Sphingosine (10 microM) had the opposite effect to the ceramides on DNA synthesis. C2- or C6-ceramides failed to inhibit the stimulation of DNA synthesis by insulin or serum. The ceramides did not modify the actions of phosphatidate, or lysophosphatidate, in decreasing the forskolin-induced increase in cAMP. C2- and C6-ceramides inhibited the stimulation of phospholipase D activity by: (a) phosphatidate, lysophosphatidate, phorbol ester, thrombin, or serum in intact fibroblasts and (b) phorbol ester or guanosine 5'-3-O-(thio)triphosphate in permeabilized fibroblasts. The ceramides can therefore modify cell signaling via phospholipase D, but this effect alone could not explain the decreased DNA synthesis. Incubation of fibroblasts with C2- or C6-ceramides or sphingomyelinase inhibited the interaction of exogenous phosphatidate or lysophosphatidate with the fibroblasts by 42 and 53%, respectively. Furthermore, a greater proportion of the phosphatidate, or lysophosphatidate, that was associated with the fibroblasts was metabolized further when the cells were pretreated with ceramides or sphingomyelinase. This effect was accompanied by an increased activity of N-ethylmaleimide-insensitive phosphatidate phosphohydrolase. Ceramides may therefore produce part of their growth inhibitory effects by blocking some of the signal transducing effects of phosphatidate and lysophosphatidate.


Production of DNA single-strand breaks in unstimulated splenocytes by dimethylnitrosamine.
In an attempt to elucidate the mechanism whereby primary hepatocytes, but not liver S9 homogenates, generate immunosupprssive metabolites of dimethylnitrosamine (DMN), the production of DNA single-strand breaks (SSB) in unstimulated splenocytes was investigated with alkaline-elution analysis. Both hepatocytes and S9 homogenates induced SSB in cultured splenocytes by DMN - minimum detectable doses with the two metabolic activation systems (MAS) were 1 microM and 5 mM, respectively. DNA elution profiles were linear in splenocytes co-cultured with DMN and hepatocytes and convex in splenocytes incubated with DMN and S9 homogenates. Aminoacetonitrile (AAN; 10 mM), a DMN demethylase inhibitor, reversed SSB in splenocytes when incubated with either MAS. Addition of exogenous calf-thymus DNA to the hepatocyte co-culture medium did not affect the production of SSB. Rocking the hepatocyte-splenocyte cultures changed the elution profile from linear to convex. All of these treatments have been previously shown to block the immunosuppression by DMN in the hepatocyte co-culture system. These results indicate that the immunosuppression by DMN is not related to DNA damage, as measured by the production of SSB, and suggest that the metabolism of DMN to intermediates capable of producing genotoxicity and immunotoxicity may be qualitatively and/or quantitatively different.


Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury.
Traumatic brain injury (TBI) is one of the leading causes of death and disability in humans. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. Using an animal model of TBI we examined the effect of dietary restriction (DR) on the neuroapoptosis and Bcl-2 family genes as the main regulators of the intrinsic apoptotic pathway. Bcl-2, Bcl-xl and Bax mRNA and protein expression in the ipsilateral cortex of adult Wistar rats exposed to DR before TBI were studied from 2 to 28 days post injury. Our results showed that DR suppressed neuroapoptosis and promoted significant upregulation of antiapoptotic Bcl-2 and Bcl-xl mRNAs in the ipsilateral cortex following injury. Expression of the proapoptotic Bax gene increased in ad libitum (AL) fed rats but remained unchanged in rats exposed to DR. Although the expression of Bcl-2, Bcl-xl and Bax proteins was changed in a similar manner in both experimental groups, DR promoted a continuous increase in the Bcl-2:Bax protein ratio throughout the recovery period. Together with our previous finding that DR mediates inhibition of the extrinsic apoptotic pathway the present work reveals that modulation of the intrinsic pathway contributes to the beneficial effect of DR in brain injury. These findings provide new insight into the effects of DR on pro-survival signaling after injury, lending further support to its neuroprotective effect.


Uncovering nuclear pore complexity with innovation.
Advances in imaging and reductionist approaches have provided a high-resolution understanding of nuclear pore complex structure and transport, revealing unexpected mechanistic complexities based on nucleoporin functions and specialized import and export pathways.


Reversible aberration of neurogenesis targeting late-stage progenitor cells in the hippocampal dentate gyrus of rat offspring after maternal exposure to acrylamide.
We have recently shown that maternal exposure to acrylamide (AA) impaired neurogenesis in rat offspring measured by the increase in interneurons producing reelin, a molecule regulating migration and correct positioning of developing neurons, in the hippocampal dentate gyrus. To clarify the cellular target of AA on hippocampal neurogenesis and its reversibility after maternal exposure, pregnant Sprague-Dawley rats were given drinking water containing AA at 0, 4, 20, 100 ppm on day 10 of pregnancy through day 21 after delivery on weaning. Male offspring were examined immunohistochemically on postnatal day (PND) 21 and PND 77. For comparison, male pups of direct AA-injection control during lactation (50 mg/kg body weight, intraperitoneally, 3 times/week) were also examined. On PND 21, maternal AA-exposure decreased progenitor cell proliferation in the subgranular zone (SGZ) from 20 ppm accompanied with increased density of reelin-producing interneurons and NeuN-expressing mature neurons within the hilus at 100 ppm, similar to the direct AA-injection control. In the SGZ examined at 100 ppm, cellular populations immunoexpressing doublecortin or dihydropyrimidinase-like 3, suggesting postmitotic immature granule cells, were decreased. On PND 77, the SGZ cell proliferation and reelin-producing interneuron density recovered, while the hilar mature neurons sustained to increase from 20 ppm, similar to the direct AA-injection control. Thus, developmental exposure to AA reversibly affects hippocampal neurogenesis targeting the proliferation of type-3 progenitor cells resulting in a decrease in immature granule cells in rats. A sustained increase in hilar mature neurons could be the signature of the developmental effect of AA.


Nursing Ethics Embedded in Nursing Theoretical Frameworks.
This author reviews and provides an introduction to Glasgow et al.'s Legal and Ethical Issues in Nursing Education: An Essential Guide. Moreover, the author shares further insight about nursing ethics embedded in nursing theoretical frameworks.


Cavum veli interpositi: prenatal diagnosis and postnatal outcome.
We describe the finding of cavum veli interpositi (CVI) on fetal ultrasound and MRI and the postnatal MRI and developmental follow-up in two cases. The first case was diagnosed on fetal ultrasound at 33 weeks' gestation and confirmed on fetal MRI. No abnormalities were detected on postnatal examinations and the brain MRI at 1 year of age showed no changes. At 4 years of age, his growth and development were normal.The second case was diagnosed with CVI on fetal ultrasound and MRI at 33.5 weeks' gestation. Postnatal examination showed no abnormalities, and brain MRI at 8 months of age revealed that the CVI was unchanged, but there was a dilated cavum septum pellucidum and cavum vergae. Her growth and development during the first 4 years of life were normal. CVI is a rare fetal ultrasound finding, which seems to be benign. However, further neurodevelopmental follow-up is needed to confirm this observation.


Aneurysmal bone cyst treated with percutaneous doxycycline: is a single treatment sufficient?
The purpose of this case series is to report on the effectiveness of a single percutaneous injection of doxycycline as a primary treatment for aneurysmal bone cyst (ABC). A retrospective cohort study was conducted on seven patients diagnosed with ABC at various anatomical sites, with the intention to treat by a single percutaneous injection of doxycycline. Mean patient age was 14 years. Signs of treatment response were seen in six of seven patients after one injection. Three of the seven received a second treatment, despite signs of response. Another had expansion of the lesion after treatment, requiring excision. In total, three patients had a single injection of doxycycline as their sole treatment and another three showed signs of response after a single injection. A single percutaneous injection of doxycycline should be considered a viable primary treatment option for ABC.


Enhanced microalgal growth and lipid accumulation by addition of different nanoparticles under xenon lamp illumination.
In this study, the growth and lipid accumulation of Scenedesmus sp. using different nanoparticles and light sources were investigated. Xenon lamp can produce a broad illumination spectrum, and exhibited better performance than light-emitting diode. SiC and g-C3N4 nanoparticles improved the biomass and lipid accumulation, whereas TiO2 and TiC nanoparticles had inhibitory influence on microalgae. Lipid production can be improved by oxidative stress produced by combination of nanoparticles and xenon lamp irradiation. At the optimal SiC nanoparticles concentration of 150 mg L-1 and photoperiod of 6:18 h, the maximum biomass concentration and total lipid content reached 3.18 g L-1 and 40.26%, respectively. The addition of SiC nanoparticles could promote the substrate utilization rate and induce stress condition, thereby enhancing the activity of acetyl-CoA carboxylase and lipid biosynthesis. This research shows that SiC nanoparticles addition combined with xenon lamp illumination is a promising strategy to promote microalgal growth and lipid accumulation.


Genotypic sex determination in teleosts: insights from the testis-determining amhy gene.
The master sex-determining genes identified so far in fishes are clearly not conserved, as evidenced by several unrelated genes reported to play critical roles in sex determination. In this study, we reviewed the molecular process of sex determination in the Patagonian pejerrey Odontesthes hatcheri, an emerging model due to the recent discovery that a Y-chromosome linked, duplicated copy of the anti-Müllerian hormone gene, amhy plays a pivotal role in sex determination. A comparative analysis with other newly found sex-determining genes of teleost fish, DMY/dmrt1bY, sdY, amhr2, and gsdf(Y) is performed and alternative ideas are proposed to explain the mechanism involved in the rise of various types of non-homologous sex-determining genes.


[The importance of the substrate for the induction of tyrosine-alpha-ketoglutarate-transaminase in RLC-cells (author's transl)].
1. Dexamethasone phosphate causes approximately a threefold increase of the tyrosine-alpha-ketoglutarate transaminase in the culture of RLC cells. 2. The induction of the enzyme depends on the presence of L-tyrosine. Omission of L-leucine or L-tryptophan, respectively, has no effect. 3. Omission of L-tyrosine influences the activity of the lactate dehydrogenase and malate dehydrogenase not at all and that of the glucose-6-phosphate-dehydrogenase only to a small extent. 4. In the absense of L-tyrosine an superinduction takes also place by actinomycin.


Apoptosis initiated by carbon tetrachloride in mitochondria of rat primary cultured hepatocytes.
To investigate the mitochondria-initiated apoptosis pathway involved in Carbon tetrachloride (CCl4) hepatotoxicity in vitro. Several cytotoxicity endpoints, including WST-8 metabolism, lactate dehydrogenase leakage and morphological changes, were examined. The 5,5'-dithio-bis(2-nitrobenzoic acid) reaction was used to measure reduced glutathione level, and the malondialdehyde level was determined using the thiobarbituric acid assay. The release of cytochrome c and Bcl-X(L) was detected by Western blot. Caspase-3 activity was measured using the fluorogenic substrate Ac-DEVD-AMC. DNA fragmentation was used to evaluate cell apoptosis. A time- and dose-dependent decrease in cellular glutathione content was observed, along with a concomitant increase in malondialdehyde levels following the application of CCl4. Caspase 3 activity was stimulated at all doses of CCl4, with the most significant activation at 3 mmol/L. Cytochrome c was released obviously after CCl4 treatment. A time-dependent decrease in Bcl-X(L) expression was observed. DNA fragmentation results revealed apoptosis and necrosis following CCl4 treatment. Oxidative damage is one of the essential mechanisms of CCl4 hepatotoxicity, which triggers apoptosis via the mitochondria-initiated pathway.


[Hydroperoxide degradation by oat isomerase. Investigation of the reaction mechanism (author's transl)].
Oat isomerase is inhibited by hydroxyoctadecadienoic acids (monohydroxy acids) to a degree comparable with inhibition by linoleic acid hydroperoxides (LHPO). Hydroxy acids seem to combine with the enzyme like LHPO do. In an experiment on LHPO breakdown by isomerase 1-14C-hydroxy acids were added and it was examined whether the epoxyhydroxy acids are formed by an intermolecular or intramolecular mechanism. In this experiment 1-14C-labeled trihydroxy acids were formed; they arise from the hydrolysis of epoxyhydroxyoctadecenoic acids formed on their part by isomerase effected LHPO-breakdown. It was determined that at least 70% of LHPO are converted by intermolecular reaction.


Protection and advocacy for the mentally ill: new hope for emotionally disturbed children?
A study was conducted to ascertain the potential effect of recent federal protection and advocacy legislation (Public Law 99-319) on the lives of mentally ill children. Findings indicate a strong potential, especially regarding efforts to improve community based services. Implications for mental health professionals and CMHCs are examined.


Structural studies and isolation of cDNA clones providing the complete sequence of rat liver dihydropteridine reductase.
The cleavage of reductively alkylated rat liver dihydropteridine reductase with cyanogen bromide afforded a mixture of peptides, six of which (CB-1 to CB-6) were isolated and purified by C8 reverse-phase high performance liquid chromatography. Portions of peptides CB-1, CB-4, and CB-6 were sequenced by automated Edman degradation and high performance liquid chromatography and the carboxyl-terminal region by conventional procedures. Further proteolytic digestion of CB-6 and isolation of the products afforded a seven-amino acid peptide. A low degeneracy probe comprising 20 nucleotides was synthesized from the sequence of this peptide and was used to screen a rat liver cDNA expression library constructed in the vector lambda gt 10. Positive clones were isolated, and detailed examination of five of these by restriction endonucleases and dideoxy sequence analyses allowed identification of the entire coding region for dihydropteridine reductase. The gene was found to code for a protein of 240 amino acids (excluding the methionine initiator) of Mr = 25,420. Each of the sequences corresponding to the peptides CB-1, CB-4, CB-6, and the carboxyl terminus were identified in the deduced protein sequence. The rat enzyme is highly homologous to the human dihydropteridine reductase; the two proteins differ in only 10 amino acids, and all are conservative substitutions. In contrast, the sequence shows little homology with that of mammalian dihydrofolate reductase: reduced pyridine nucleotide-requiring enzymes with superficial mechanistic similarities.


Glycyl-L-glutamine disposition in rat choroid plexus epithelial cells in primary culture: role of PEPT2.
The purpose of this research was to determine the polarity and directionality of the PEPT2-mediated uptake and transepithelial transport of the neuropeptide glycyl-L-glutamine (GlyGln) in choroid plexus. The transport kinetics of [3H]GlyGln was studied in neonatal rat choroid plexus epithelial cells in primary culture grown on laminin-coated Transwell filter inserts. Using a bicarbonate artificial cerebrospinal fluid (CSF) buffer (pH 7.4) at 37 degrees C, GlyGln studies were performed as a function of time, substrate concentration, and the presence of potential inhibitors (at 1 mM). GlyGln (2 microM) accumulation was about three to four times greater when introduced from the apical (CSF-facing) as opposed to the basal (blood-facing) side of the cell monolayer, and transepithelial transport was about two times greater in the apical-to-basal direction. The apical uptake of radiolabeled GlyGln (2 microM) was inhibited significantly by dipeptides (i.e., unlabeled GlyGln and cysteinylglycine) and some neuropeptides (i.e., carnosine, N-acetylaspartylglutamate, kyotorphin), but was unaffected by amino acids (i.e., glycine, glutamine) as well as by [D-Arg2]-kyotorphin and glutathione. The concentration-dependent apical uptake of GlyGln (2-1000 microM) was characterized by a high-affinity process (i.e., Vmax of 72 pmol/mg/min; Km of 136 microM), consistent with the properties of PEPT2. The intracellular hydrolysis of GlyGln was extensive, however, with only 40% of the dipeptide remaining intact after 1 h. The results demonstrate that PEPT2 plays an important role in regulating the apical uptake of GlyGln at the blood-CSF interface. Once inside the cell, GlyGln is rapidly degraded to its constitutive amino acids for further processing.


Study on effectiveness of transfusion program in thalassemia major patients receiving multiple blood transfusions at a transfusion centre in Western India.
Children suffering from beta-thalassemia major require repeated blood transfusions which may be associated with dangers like iron overload and contraction of infections such as HIV, HCV, and HBsAg which ultimately curtail their life span. On the other hand, inadequate transfusions lead to severe anemia and general fatigue and debility. Data were obtained from 142 beta-thalassemia major patients aged 3 years or more receiving regular blood transfusions at a transfusion centre in Western India from 1 April 2009 to 30 June 2009. The clinical data and laboratory results were subsequently analyzed. Of the 142 patients, 76 (53.5%) were undertransfused (mean Hb <10 gm%). 96 (67%) of the patients were taking some form of chelation therapy but out of them only 2 (2%) were adequately chelated (S. ferritin <1000 ng/ml). 5 (3.5%) of the patients were known diabetics on insulin therapy. 103 (72%) of the patients were retarded in terms of growth. The prevalence of transfusion-transmitted infections (TTIs) such as HCV, HIV, and HBsAg was respectively 45%, 2%, and 2%, with the prevalence of HCV being significantly more than the general population. The HCV prevalence showed positive correlation with the age of the patients and with the total no of blood transfusions received. As many as 15% (6 out of 40) children who were born on or after 2002 were HCV positive despite the blood they received being subjected to screening for HCV. The study suggests the need to step up the transfusions to achieve hemoglobin goal of 10 gm% (as per the moderate transfusion regimen) and also to institute urgent and effective chelation measures with the aim of keeping serum ferritin levels below 1000 ng/ml to avoid the systemic effects of iron overload. In addition, strict monitoring of the children for endocrinopathy and other systemic effects of iron overload should be done. Rigid implementation of quality control measures for the ELISA kits used to detect HCV in donor blood needs to be done urgently. Alternately, more sensitive and specific measures (like NAT testing) should be employed for detection of HCV. In the absence of a definitive cure accessible and available to all patients, strict implementation of the above suggested measures will go a long way in improving the quality (and quantity) of life in patients of beta-thalassemia major.


Lung clearance index in children with sickle cell disease.
The lung clearance index (LCI) derived from the multiple breath washout test (MBW), is both feasible and sensitive to early lung disease detection in young children with cystic fibrosis and asthma. The utility of LCI has not been studied in children with sickle cell disease (SCD). We hypothesized that children with SCD, with or without asthma or airway hyperreactivity (AHR), would have an elevated LCI compared to healthy controls. Children with SCD from a single center between the ages of 6 and 18 years were studied at baseline health and completed MBW, spirometry, plethysmography and blood was drawn for serum markers. Results were compared to healthy controls of similar race, age, and gender. Healthy controls (n = 35) had a significantly higher daytime oxygen saturation level, weight and body mass index but not height compared to participants with SCD (n = 34). Total lung capacity (TLC) z-scores were significantly higher in the healthy controls compared to those with SCD (0.87 [1.13] vs. 0.02 [1.27]; p = .005) while differences in forced expiratory volume in 1 s z-scores approached significance (0.26 [0.97] vs. -0.22 [1.09]; p = .055). There was no significant difference in LCI between the healthy controls compared to participants with SCD (7.29 [0.72] vs. 7.40 [0.69]; p = .514). LCI did not differentiate SCD from healthy controls in children between the ages of 6 and 18 years at baseline health. TLC may be an important pulmonary function measure to follow longitudinally in the pediatric SCD population.


In Vitro and In Vivo Interaction Studies Between Lesinurad, a Selective Urate Reabsorption Inhibitor, and Major Liver or Kidney Transporters.
Lesinurad is a selective uric acid reabsorption inhibitor (SURI) under investigation for the treatment of gout. This study elucidated the interaction of lesinurad with major liver and kidney transporters in vitro and evaluated the drug-drug interactions (DDIs) of lesinurad and atorvastatin, metformin, and furosemide in clinical studies. Lesinurad interaction with membrane transporters was evaluated in validated transporter-expressing cell systems and analyzed by liquid scintillation counting. Healthy male subjects (ages 18-65 years; body mass index 18-32 kg/m(2)) received atorvastatin (40 mg; n = 28) with or without lesinurad 200 or 400 mg, or received metformin (850 mg; n = 12) or furosemide (40 mg; n = 11) with or without lesinurad 400 mg. Plasma concentrations of each concomitant drug were determined by validated liquid chromatography with tandem mass spectrometry methods. Lesinurad interacted in vitro with OATP1B1, OCT1, and OAT1/3 transporters. Co-administration of lesinurad 200 mg did not significantly alter plasma exposure (maximum concentration [C max] and area under the concentration-time curve [AUC]) of total atorvastatin (atorvastatin + hydroxyl-metabolites) or atorvastatin, while co-administration of lesinurad 400 mg increased the C max of total atorvastatin and atorvastatin by 17-26 %, but had no effect on AUC. Co-administration of lesinurad 400 mg had no effect on the plasma exposure of metformin. Furosemide plasma AUC was reduced by 31 % in the presence of lesinurad 400 mg, but furosemide renal clearance and diuretic activity were unchanged. No clinically relevant DDIs were observed between lesinurad and substrates of major liver or kidney transporters.


2D-Layer-Structure Bi to Quasi-1D-Structure NiBi3 : Structural Dimensionality Reduction to Superior Sodium and Potassium Ion Storage.
Layer-structured bismuth (Bi) is an attractive anode for Na-ion and K-ion batteries due to its large volumetric capacity and suitable redox potentials. However, the cycling stability and rate capability of the Bi anode are restricted by the large volume expansion and sluggish Na/K-storage kinetics. Herein, a structural dimensionality reduction strategy is proposed and developed by converting 2D-layer-structured Bi into a quasi-1D structured NiBi3 with enhanced reaction kinetics and reversibility to realize high-rate and stable cycling performance for Na/K-ion storage. As a proof of concept, the quasi-1D intermetallic NiBi3 with low formation energy, metallic conductivity, and 3D Na/K-ion diffusion pathways delivers outstanding capacity retention of 94.1% (332 mAh g-1 ) after 15 000 cycles for Na-ion storage, and high initial coulombic efficiency of 93.4% with improved capacity retention for K-ion storage. Moreover, investigations on the highly reversible Na/K-storage reaction mechanisms and cycling-driven morphology reconstruction further reveal the origins of the high reversibility and the accommodation to volume expansion. The finding of this work provides a new strategy for high-performance anode design by structural dimensionality manipulation and cycling-driven morphology reconstruction.


Roles for Phospholipase D1 in the Tumor Microenvironment.
The lipid-modifying signal transduction enzyme phospholipase D (PLD) has been proposed to have roles in oncogenic processes for well-on 30 years, with most of the early literature focused on potential functions for PLD in the biology of the tumor cells themselves. While such roles remain under investigation, evidence has also now been generated to support additional roles for PLD, in particular PLD1, in the tumor microenvironment, including effects on neoangiogenesis, the supply of nutrients, interactions of platelets with circulating cancer cells, the response of the immune system, and exosome biology. Here, we review these lines of investigation, accompanied by a discussion of the limitations of the existing studies and some cautionary notes regarding the study and interpretation of PLD function using model systems.


InterACTIV: an exploratory study of the use of a game console to promote physical activation of hospitalized adult patients with cancer.
To explore the application of the Nintendo Wii game console to motivate hospitalized adult patients with cancer to be physically active during treatment periods. An exploratory study with a mixed-method approach, including descriptive statistics and Mayring's qualitative data evaluation method. The Department of Radiation Oncology at the University Hospital in Halle (Saale) in Germany. Convenience sample of 7 adult inpatients. All patients received physical training for five days for 30 minutes per day with Nintendo Wii. After the last training session, patients were interviewed using a semistructured guideline. Applicability of a motion-activated game console during inpatient treatment periods, patients' distraction from the hospital environment. In general, the use of a motion-activated game console in a hospital environment was evaluated positively. Participants showed a high degree of acceptance using this kind of physical activity. Because of the Nintendo Wii, the majority of individuals felt stimulated to become physically active during hospitalization. In addition, all patients lost time awareness and felt distracted from the daily hospital routine. A majority of the patients reported an improved mood state from the game sessions. The results indicate that a motion-activated game console could be useful to motivate adult patients with cancer to be physically active during hospitalization. Nurses can recommend the use of game consoles such as the Nintendo Wii for physical exercise; in addition, the motivational effects of playing motion-activated game consoles might be particularly helpful for patients with cancer-related fatigue to overcome barriers and begin exercise.


Cost-Effectiveness Analysis of Lung Cancer Screening in the United States: A Comparative Modeling Study.
Recommendations vary regarding the maximum age at which to stop lung cancer screening: 80 years according to the U.S. Preventive Services Task Force (USPSTF), 77 years according to the Centers for Medicare & Medicaid Services (CMS), and 74 years according to the National Lung Screening Trial (NLST). To compare the cost-effectiveness of different stopping ages for lung cancer screening. By using shared inputs for smoking behavior, costs, and quality of life, 4 independently developed microsimulation models evaluated the health and cost outcomes of annual lung cancer screening with low-dose computed tomography (LDCT). The NLST; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; SEER (Surveillance, Epidemiology, and End Results) program; Nurses' Health Study and Health Professionals Follow-up Study; and U.S. Smoking History Generator. Current, former, and never-smokers aged 45 years from the 1960 U.S. birth cohort. 45 years. Health care sector. Annual LDCT according to NLST, CMS, and USPSTF criteria. Incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). The 4 models showed that the NLST, CMS, and USPSTF screening strategies were cost-effective, with ICERs averaging $49 200, $68 600, and $96 700 per QALY, respectively. Increasing the age at which to stop screening resulted in a greater reduction in mortality but also led to higher costs and overdiagnosis rates. Probabilistic sensitivity analysis showed that the NLST and CMS strategies had higher probabilities of being cost-effective (98% and 77%, respectively) than the USPSTF strategy (52%). Scenarios assumed 100% screening adherence, and models extrapolated beyond clinical trial data. All 3 sets of lung cancer screening criteria represent cost-effective programs. Despite underlying uncertainty, the NLST and CMS screening strategies have high probabilities of being cost-effective. CISNET (Cancer Intervention and Surveillance Modeling Network) Lung Group, National Cancer Institute.


Novel remodeling of the mouse heart mitochondrial proteome in response to acute insulin stimulation.
Mitochondrial dysfunction contributes to the pathophysiology of diabetic cardiomyopathy. The aim of this study was to investigate the acute changes in the mitochondrial proteome in response to insulin stimulation. Cardiac mitochondria from C57BL/6 mice after insulin stimulation were analyzed using two-dimensional fluorescence difference gel electrophoresis. MALDI-TOF MS/MS was utilized to identify differences. Two enzymes involved in metabolism and four structural proteins were identified. Succinyl-CoA ligase [ADP forming] subunit beta was identified as one of the differentially regulated proteins. Upon insulin stimulation, a relatively more acidic isoform of this protein was increased by 53% and its functional activity was decreased by ∼32%. This proteomic remodeling in response to insulin stimulation may play an important role in the normal and diabetic heart.


Flow cytofluorimetric analysis of lymphocyte subset alterations in cattle infected with bovine viral diarrhea virus.
Clinically normal, bovine viral diarrhea virus (BVDV)-seronegative, 7 to 9-month-old steers were inoculated intranasally with NY-1, a noncytopathic strain of BVDV, or exposed intramuscularly to killed BVDV. Indirect immunofluorescence staining with monoclonal antibodies specific for bovine leukocyte subsets followed by flow cytometric analysis was used to monitor subsequent hematologic alterations. Infection with BVDV resulted in a transient leukopenia which was characterized by decreases in the absolute numbers of circulating T lymphocytes, including BoT4+ ("helper") and BoT8+ ("cytotoxic/suppressor") subsets, B lymphocytes, and neutrophils. There was no significant variation in numbers of non-T, non-B ("null") lymphocytes or monocytes. Exposure to inactivated BVDV in a combination vaccine did not cause significant alteration in the circulating numbers of any major leukocyte subset; however, significant variation was seen in the BoT4/BoT8 ratios and in the numbers of cells expressing major histocompatibility complex (MHC) class II antigens.


Genome-wide analysis of overlapping genes regulated by iron deficiency and phosphate starvation reveals new interactions in Arabidopsis roots.
Iron (Fe) and phosphorus (P) are essential mineral nutrients in plants. Knowledge regarding global changes in the abundance of Fe-responsive genes under Pi deficiency as well as the processes these genes are involved in remains largely unavailable at the genome level. In the current study, we comparatively analyzed RNA sequencing data sets relative to Fe deficiency (NCBI: SRP044814) and Pi starvation (NCBI: SRA050356.1). Analysis showed a total of 579 overlapping genes that are responsible for both Fe deficiency and Pi starvation in Arabidopsis roots. A subset of 137 genes had greater than twofold changes in transcript abundant as a result of the treatments. Gene ontology (GO) analysis showed that the stress-related processes 'response to salt stress', 'response to oxidative stress', and 'response to zinc ion' were enriched in the 579 genes, while Fe response-related processes, including 'cellular response to nitric oxide', 'cellular response to iron ion', and 'cellular iron ion homeostasis', were also enriched in the subset of 137 genes. Co-expression analysis of the 579 genes using the MACCU toolbox yielded a network consisting of 292 nodes (genes). Further analysis revealed that a subset of 90 genes were up-regulated under Fe shortage, but down-regulated under Pi starvation. GO analysis in this group of genes revealed an increased cellular response to iron ion/nitric oxide/ethylene stimuli. Promoter analysis was performed in 35 of the 90 genes with a 1.5-fold or greater change in abundance, showing that 12 genes contained the PHOSPHATE STARVATION RESPONSE1-binding GNATATNC cis-element within their promoter regions. Quantitative real-time PCR showed that the decreased abundance of Fe acquisition genes under Pi deficiency exclusively relied on Fe concentration in Pi-deficient media. Comprehensive analysis of the overlapping genes derived from Fe deficiency and Pi starvation provides more information to understand the link between Pi and Fe homeostasis. Gene clustering and root-specific co-expression analysis revealed several potentially important genes which likely function as putative novel players in response to Fe and Pi deficiency or in cross-talk between Fe-deficient responses and Pi-deficient signaling.


Copper Silicate Hydrate Hollow Spheres Constructed by Nanotubes Encapsulated in Reduced Graphene Oxide as Long-Life Lithium-Ion Battery Anode.
Hierarchical copper silicate hydrate hollow spheres-reduced graphene oxide (RGO) composite is successfully fabricated by a facile hydrothermal method using silica as in situ sacrificing template. The electrochemical performance of the composite as lithium-ion battery anode was studied for the first time. Benefiting from the synergistic effect of the hierarchical hollow structure and conductive RGO matrix, the composite exhibits excellent long-life performance and rate capability. A capacity of 890 mAh/g is achieved after 200 cycles at 200 mA/g and a capacity of 429 mAh/g is retained after 800 cycles at 1000 mA/g. The results indicate that the strategy of combining hierarchical hollow structures with conductive RGO holds the potential in addressing the volume expansion issue of high capacity anode materials.


A Quantitative Framework to Identify and Prioritize Opportunities in Biomedical Product Innovation: A Proof-of-Concept Study.
Prioritization and funding for health initiatives, including biomedical innovation, may not consistently target unmet public health needs. To (1) develop a quantitative, databased framework to identify and prioritize opportunities for biomedical product innovation investments based on a multicriteria decision-making model (MCDM) that includes comprehensive measures of public health burden and health care costs, and (2) pilot test the model. The Department of Health and Human Services (HHS) convened public and private experts to develop a model, select measures, and complete a longitudinal pilot study to identify and prioritize opportunities for investment in biomedical product innovations that have the greatest public health benefit. Cross-sectional and longitudinal data (2012-2019) for 13 pilot medical disorders were obtained from the Institute for Health Metrics Global Burden of Disease database (IHME GBD) and the National Center for Health Statistics (NCHS). The main outcome measure was an overall gap score reflecting high public health burden (composite measure of mortality, prevalence, years lived with disability, and health disparities), or high health care costs (composite measure of total, public, and out-of-pocket health spending) relative to low biomedical innovation. Sixteen innovation metrics were selected to reflect the pipeline of biomedical products from research and development to market approval. A higher score indicates a greater gap. Normalized composite scores were calculated for public health burden, cost, and innovation investment using the MCDM Technique for Order of Preference by Similarity to Ideal Solution method. Among the 13 conditions tested in the pilot study, diabetes (0.61), osteoarthritis (0.46), and drug-use disorders (0.39) had the highest overall gap score reflecting high public health burden, or high health care costs relative to low biomedical innovation in these medical disorders. Chronic kidney disease (0.05), chronic obstructive pulmonary disease (0.09), and cirrhosis and other liver diseases (0.10) had the least amount of biomedical product innovation despite similar public health burden and health care cost scores. In this cross-sectional pilot study, we developed and implemented a data-driven, proof-of-concept model that can help identify, quantify, and prioritize opportunities for biomedical product innovation. Quantifying the relative alignment between biomedical product innovation, public health burden, and health care cost may help identify and prioritize investments that can have the greatest public health benefit.


Teaching head and neck cancer patients coping strategies: results of a feasibility study.
To test the feasibility of providing a psycho-educational intervention for people with head and neck (H&N) cancer. A prospective non-randomized design was used. Subjects were patients with H&N cancer. They were offered the Nucare coping strategies program in one of three formats: small group and one-to-one formats with therapists; and a home format, with material for home use, without a therapist. Outcomes measures (quality of life (QOL) and anxiety and depression) were collected at baseline and following the intervention. Analyses were performed using non-parametric statistics. Of 128 people invited to participate, 66 agreed, 59 completed the intervention and 50 had outcomes data. Following the intervention, there were significant improvements in physical and social functioning and global QOL, and reduced fatigue, sleep disturbance and depressive symptoms. These data suggest that the intervention may have some beneficial effects, although an appropriately designed study is required to confirm this.


EVALUATION OF QUALITY OF LIFE IN PATIENTS TREATED FOR METASTATIC DISEASE OF THE PROXIMAL FEMUR.
Patients with metastatic bone lesions have a limited life expectancy. These metastatic lesions compromise the proximal femur, and fractures are quite common. The survival of these patients depends on the behavior of the primary tumor. The aim of this study was to evaluate the quality of life of patients with extensive metastatic lesion of the proximal femur with pathological or imminent fracture, treated with non-conventional endoprosthesis. From May 2008 to August 2012, twenty-five (25) patients with bone metastases of the proximal femur, with pathological or imminent fracture were recruited into this study. These patients had survived for at least six weeks after surgery and the TESS questionnaire (Toronto Extremity Salvage Score) was administered. The final score of the TESS was an average of 57 points (SD 23.78 points). There was no significant difference in TESS values considering: sex, presence of fracture, or site of the bone lesion. The TESS questionnaire provides information about the function and quality of life of patients with malignant tumors of the lower limbs, from the patient's perspective. The results can be considered positive, when compared to the limited life expectancy and complexity of this group of patients. Level of evidence III, Therapeutic studies, retrospective comparative study.


Reduction of water consumption in bioethanol production from triticale by recycling the stillage liquid phase.
The distillery stillage is a major and arduous byproduct generated during ethanol production in distilleries. The aim of this study was to evaluate the possibility of the stillage recirculation in the mashing process of triticale for non-byproducts production and reducing the fresh water consumption. The number of recirculation cycles which can be applied without disturbances in the ethanol fermentation process was investigated. Winter triticale BOGO and "Ethanol Red" Saccharomyces cerevisiae yeast were used in the experiments. The method of non-pressure cooking was used for gelatinizingthe triticale, commercial α-amylase SPEZYME ETHYL and glucoamylase FERMENZYME L-400 were applied for starch liquefaction and saccharification. The process was conducted at 30°C for 72 h, next after distillation the stillage was centrifuged and the liquid fraction was used instead of 75% of process water. Ethanol yield from triticale fermentations during 40 cycles ranged between 82% and 95% of theoretical yield preserving yeast vitality and quantity on the same level. The obtained distillates were characterized with enhanced volatile compounds (fusel oil, esters, aldehydes, methanol) as well as protein and potassium concentrations. The liquid part of stillage was proved that can be reused instead of water in bioethanol production from triticale, without disturbing the fermentation process. This investigated solution of distillery byproducts utilization (liquid phase of stillage) constitutes the way which could significantly decrease the bioethanol production costs by reducing the water consumption, as well as wastewater production.


Two Cases of Posterior Cerebral Artery P2 Segment Occlusion with Motor Weakness Improved by Acute Mechanical Thrombectomy.
Clinical evidence to support the use of mechanical thrombectomy (MT) for posterior cerebral artery P2 segment occlusion (P2O) has not been established, and hemiplegia due to P2O improved by MT to our knowledge has not yet been reported. We report 2 cases of P2O with hemiplegia improved by MT. In case 1, a 68-year-old man was admitted with right hemiplegia and dysesthesia (National Institutes of Health Stroke Scale score 14). Head magnetic resonance imaging showed acute ischemia in the left inferolateral thalamus and posterior limb of the internal capsule. Angiography showed left P2O, which was recanalized after MT. Hemiplegia improved immediately following recanalization, and modified Rankin Scale score at discharge was 0. In case 2, a 69-year-old man was admitted with left hemiplegia and dysesthesia (National Institutes of Health Stroke Scale score 8). Head magnetic resonance imaging showed acute ischemia in the right inferolateral thalamus and posterior limb of the internal capsule. Angiography showed right P2O, which was recanalized after MT, as in case 1. His symptoms resolved completely. P2O may cause severe motor deficit. In such cases, MT may contribute to safely improving patients' deficits.


Endothelin-1 and atherosclerosis: potential complications associated with endothelin-receptor blockade.
Atherosclerotic vascular disease remains the single most prevalent cause of death and morbidity in the western world. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that also possesses mitogenic activity on many cell types, including vascular smooth muscle cells. Raised plasma and tissue levels of ET-1 have been described in atherosclerosis in animal models and in man, suggesting that this peptide plays a pathophysiological role in this condition. Two main ET-1 receptors have been cloned (ET(A) and ET(B)). Mixed ET(A/B) and receptor subtype selective antagonists are now available. Since ET-1 is generally believed to be a 'pathophysiological peptide', we discuss the therapeutic potential of ET-1 antagonists in atherosclerosis and consider whether, at certain sites in this process, ET-1 may play a beneficial role. In such situations ET antagonism may be undesirable.


Commercial Synovial Antibody Testing is No Better Than Traditional Culture in Identification of Pathogen(s) Causing Periprosthetic Joint Infection.
Identification of infective organism causing periprosthetic joint infections (PJIs) is crucial to tailor the best combination of surgical and antimicrobial treatment. Traditional culture, with all its limitations, has been utilized for this purpose. A synovial fluid antibody assay against some common pathogens has been introduced by a commercial entity recently. This study aimed to determine if the antibody testing could be used as a proxy to traditional culture, and whether it provided additional information, in the setting of PJI. A retrospective study was conducted of patients who underwent revision total hip and knee arthroplasty between January 2019 and 2020. Aspirated synovial fluid was sent for analyses including the commercial antibody testing. All patients had samples harvested for culture per standard of care. Results of the antibody testing and culture, in terms of concordance, were compared. Receiver operating characteristic curve and Youden's criterion were used to compare the 2 methods. A total of 419 patients were included. Using the International Consensus Meeting criteria as reference standard for PJI, antibody testing had a sensitivity and specificity of 40.5% and 93.4%, respectively. There were 59.5% false negative results with antibody testing compared with 50% for culture. Of the 12 patients who had positive results in both tests, 5 (41.7%) had discordant pathogens identified in each test. Synovial fluid antibody testing does not provide clinical benefit when compared to traditional cultures for PJI diagnosis. The antibody testing had a low sensitivity and a high rate of discordance with culture, when both tests were positive.


Thermal injury increases the number of eosinophil progenitors in rat spleen and bone marrow.
We have investigated the effects of thermal injury upon myelopoiesis. IL-3, GM-CSF, and IL-5 were used to stimulate myeloid colony formation. IL-3 induces early myeloid progenitors and a more developed myeloid progenitor, the granulocyte-macrophage colony-forming unit (GM-CFU), to multiply and develop into mature myeloid cells. GM-CSF induces GM-CFU to become mature myeloid cells, while IL-5 induces eosinophil progenitors to become mature eosinophils. Stem Cell Factor (SCF) + IL-6 and FLT3 ligand, which have no effect on colony formation by themselves, were used to enhance the effects of IL-3 and GM-CSF, respectively. We found that thermal injury increased the number of early myeloid progenitors and GM-CFU in the spleen with either IL-3 or GM-CSF as a stimulant. Thermal injury increased the number of early myeloid progenitors in the bone marrow when GM-CSF, but not IL-3, was used to stimulate colony growth. Also, thermal injury increased the numbers of eosinophil progenitors in rat spleen and bone marrow and increased splenic levels of IL-5 mRNA.


Body mass index, blood glucose, and mortality in patients with ischemic stroke in the intensive care unit: A retrospective cohort study.
Excessive BMI was associated with lower mortality after stroke. However, some believed that excessive BMI can lead to a poor prognosis because of some physiological mechanism, such as glucose metabolism disorder. Therefore, this study aims to discuss the association between mortality, BMI, and blood glucose. This was a retrospective observational study and all data were extracted from the Medical Information Mart for Intensive Care III database. The exposure was BMI classified into the normal weight group and the excessive weight group. The outcome concluded 30-day, 90-day, and 1-year mortality. The association between two groups and mortality was elucidated by Cox regression models, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The underlying effect of blood glucose on the "obesity paradox" was analyzed by causal mediation analysis. According to Cox regression models, a significant beneficial effect of excessive BMI in terms of mortality was observed: 30-day mortality (HR 0.57, 95% CI 0.35-0.90, P = 0.017), 90-day mortality (HR 0.53, 95% CI 0.36-0.78, P = 0.001), and 1-year mortality (HR 0.65, 95% CI 0.46-0.91, P = 0.013). After PSM and IPTW, we got a similar conclusion. The causal mediation analysis showed that the protective effect of excessive BMI on 30-day mortality reduced with the increase of blood glucose. For ischemic stroke patients in the Intensive Care Unit, those with excessive BMI are associated with both lower short-term mortality and lower long-term mortality, while the protective effect on 30-day mortality weakened accompanied by the increase of blood glucose.


First trimester screening for aneuploidy: may combined test and fetal DNA work together?
The purpose of the study was to evaluate the screening performance of combined test (based on the measurement of nuchal translucency, pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, and maternal age) and fetal DNA screening (NIPS) for trisomies 21 (T21), 18 (T18), and 13 (T13). Women who accepted screening had a first-trimester combined test (pregnancy-associated plasma protein A, free β-human chorionic gonadotropin, nuchal translucency interpreted with maternal age) and fetal DNA. Among 302 women screened (including 4 with affected pregnancies), our study demonstrated that DNA screening for trisomies 21, 18, and 13 achieved a detection rate of 100% with a false-positive rate of 0.02%, overcoming the traditional combined test with 75% of sensitivity and 4.7% of false-positive rate. In particular, fetal DNA may be useful in case of intermediate risk, in order to avoid invasive diagnostic procedures such villocentesis and amniocentesis. Because of fetal DNA costs, it can be used in clinical practice as a second step screening in case of intermediate or high risk at combined test. Fetal DNA screening may be successfully implemented in routine care, achieving a high detection rate, low false-positive rate, and, consequently, greater safety with fewer invasive diagnostic tests than other methods of screening.


Influence of extended depth of focus intraocular lenses on visual field sensitivity.
To investigate the influence of EDOF IOLs, TECNIS Symfony® (Johnson & Johnson Surgical Vision, Inc.), on visual field sensitivity and to compare the IOLs with other kinds of IOLs. The subjects included the normal fellow eyes of patients who underwent the Humphrey Field Analyzer (HFA) 30-2 with Swedish Interactive Threshold Algorithm Fast within 6 months after cataract due to glaucoma or suspected glaucoma. Each parameter of HFA was compared among eyes implanted with TENIS Symfony® (EDOF group), diffractive bifocal IOLs (bifocal group), and monofocal IOLs (monofocal group). The total of 76 eyes, including 24 eyes in the EDOF group, 26 eyes in the bifocal group, and 26 eyes in the monofocal group, were included in this study. Mean deviation (MD) of HFA was -0.24±0.58 dB in the EDOF group, -1.38±0.58 dB in the bifocal group, and 0.02±0.44 dB in the monofocal group. Foveal threshold (FT) of HFA was 35.8±1.6 dB in the EDOF group, 33.6±1.7 dB in the bifocal group, and 36.6±1.4 dB in the monofocal group. In both MD and FT, there was significant difference between the bifocal group and the others (p<0.001). There was no difference between the EDOF group and the monofocal group. Moreover, there was no significant difference between the three groups about pattern standard deviation (PSD) of HFA. TECNIS Symfony® may have little influence on visual field sensitivity, whereas diffractive bifocal IOLs decrease visual field sensitivity.


Monitoring of antioxidant properties of uric acid in humans for a consideration measuring of levels of allantoin in plasma by liquid chromatography.
Uric acid is the end product of purine metabolism in humans. It has been pointed out that uric acid acts as an antioxidant and is capable to react with biologically relevant oxidants to form allantoin. Therefore, measurement of allantoin in humans was proposed as a marker of oxidative stress. We estimated allantoin in human plasma obtained from the patients with chronic renal failure before hemodialysis (n=30), patients with non-insulin dependent diabetes mellitus (n=30) and blood donors (n=30) using a method based on selective isolation of allantoin from deproteinized plasma samples on AG 1-X8 resin and its derivatization to glyoxylate-2,4-dinitrophenylhydrazone. The method is free from urate and glyoxylate interferences. Separation of glyoxylate-2,4-dinitrophenylhydrazone from other hydrazones was achieved on reversed phase HPLC with gradient elution and UV/VIS detection at 360 nm. The analytical performance of this method is satisfactory with intra-assay CV 5.7%, inter-assay CV 8.3% and recovery 94.1%. We have determined other parameters of oxidative stress (malondialdehyde, total antioxidant status, superoxide dismutase and glutathione peroxidase) too. The preliminary reference range of allantoin in a group of blood donors is 4.76+/-2.99 micromol/L. In the patients with chronic renal failure and the patients with non-insulin dependent diabetes mellitus we found allantoin levels in plasma (27.1+/-13.8) micromol/L and (11.08+/-5.90) micromol/L, respectively. It seems that allantoin is a possible indicator of free radical damage in vivo.


Efficacy of a heat and moisture exchange device during high-frequency jet ventilation.
A hygroscopic condensor humidifier has been tested during high-frequency jet ventilation, in an experimental set up. The influence of various ventilator settings on relative humidity, temperature and water content of the inspiratory and expiratory gases was investigated. The device provides adequate conditioning of the inspired gases with regard to relative humidity, temperature and water content at various ventilator settings.


Three patterns of mitochondrial DNA nucleotide divergence in the meadow vole, Microtus pennsylvanicus.
The DNA sequence was determined for the cytochrome c oxidase II (COII), tRNALys, and ATPase 8 genes from the mitochondrial genome of the meadow vole, Microtus pennsylvanicus. When compared to other rodents, three different patterns of evolutionary divergence were found. Nucleotide variation in tRNALys is concentrated in the T psi C loop. Nucleotide variation in the COII gene in three genera of rodents (Microtus, Mus, Rattus) consists predominantly of transitions in the third base positions of codons. The predicted amino acid sequence in highly conserved (greater than 92% similarity). Analysis of the ATPase 8 gene among four genera (Microtus, Cricetulus, Mus, Rattus) revealed more detectable transversions than transitions, many fixed first and second position mutations, and considerable amino acid divergence. The rate of nucleotide substitution at nonsynonymous sites in the ATPase 8 gene is 10 times the rate in the COII gene. In contrast, the estimated absolute mutation rate as determined by analysis of nucleotide substitutions at fourfold degenerate sites probably is the same for the two genes. The primary sequences of the ATPase 8 and COII peptides are constrained differently, but each peptide is conserved in terms of predicted secondary-level configuration.


Skin-to-Skin Contact for Transferring Preterm Infants from the Delivery Room to the Neonatal Intensive Care Unit Is Promising Despite Moderate Heat Loss during the Procedure.
The principal aim of this prospective observational study was to assess the feasibility of skin-to-skin contact (SSC) with fathers during the transfer of preterm infants from the delivery room to the neonatal intensive care unit (NICU) in comparison with incubator transfers. The study population comprised preterm singletons born between May and December 2019 in our maternity ward who did not require invasive ventilation. Physiological parameters (axillary temperature, heart rate, and fraction of inspired oxygen) of the newborns were recorded at prespecified steps during the transfers. The impact of the transfer mode on early blood glucose level, blood gas, and neonatal morbidities and mortality and the delay in the first SSC in the NICU and breastfeeding implementation and maintenance were also analyzed. Twenty-eight preterm infants were transferred in incubators, and 29 infants were transferred using SSC. The SSC transfer induced heat loss (mean, -0.45°C; standard deviation [SD], 0.58). However, the decrease in temperature was similar to that observed during transfer in the incubator (mean, -0.30°C; SD, 0.49; p = 0.3). The transfer using SSC was not an independent factor associated with hypothermia at admission in the NICU (adjusted odds ratio, 2.6 [0.68-9.75]; p = 0.16). Neonatal morbidities and mortality were similar regardless of the transfer mode. The SSC transfer promoted early SSC in the neonatal unit (median hour [range], incubator 26 [2-126] vs SSC 13 [1-136], p = 0.03) and breastfeeding at discharge (incubator 35.7% vs SSC 69%, p = 0.01). The SSC transfer of preterm infants was feasible and promoted earlier SSC and breastfeeding. Nevertheless, the SSC transfer, like the transfer in the incubator, induced moderate heat losses that exacerbated hypothermia at admission in the NICU. The improvement of thermal conservation during infant positioning and the continuation of SSC in the unit could help in preventing hypothermia. · The SSC transfer was associated with heat loss during the transfer procedure.. · The SSC transfer promoted earlier SSC in the neonatal unit.. · The SSC transfer was likely to encourage breastfeeding..


[Preparation of 1-(5'-nitrofurfuryl)-5-halouracils].
Some 1-(5'-nitrofurfuryl)-5-halouracils were synthetized and tested in vitro for antimicrobial activity. N.M.R. spectra of the compounds proved 1-substitution on uracil.


[Giant enchondroma of the thumb distal phalanx. Presentation of a case and review of the literature].
We report on a case of giant enchondroma of the distal phalanx of the thumb, with a significant degree of clinical and radiographic deformity. It is extremely rare in this location and its treatment should be surgical, with curettage of the lesional cavity and filling with autologous bone graft. In this case, we performed a differential diagnosis of a giant cell tumour and aneurysmatic bone cyst (X-ray and nuclear magnetic resonance [NMR]).


PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma.
In our study, we demonstrate that ccRCC cell lines with impaired function of pVHL to degrade HIFα express elevated levels of PD-L1. In vitro analysis provided evidence that both reconstitution of pVHL and silencing of HIF2α, but not of HIF1α, lead to reduced PD-L1 expression. The strong correlation of expression between the HIF2α-specific HIF target Glut1 and PD-L1 confirmed this finding in ccRCC cell lines and tissue. Soluble PD-L1 levels remained constant in the sera of ccRCC patients regardless of the PD-L1 expression status in their tumors. In conclusion, our data suggest PD-L1 as HIF2α target, which is upregulated in pVHL deficient ccRCC. The combination of PD-L1 targeting drugs with HIF inhibiting agents may be an additional option for the treatment of ccRCC.


A distraction technique using reduction multi-axial screws for open reduction of high-grade lumbar posterior dislocation:a case report and literature review.
L3 vertebral fractures with posterior dislocation are rare and usually secondary to high-energy trauma. To assess the outcome of a valuable distraction technique, using long-tail multiaxial pedicle screw which we have employed in reduction of L3 vertebral fracture with posterior dislocation, and emphasize the importance of preoperative blood vessel evaluation. A 47-year-old patient fell from a height of 4 m and was paralyzed. Computed tomography scan revealed a three-column ligamentous injury with posterior fracture-dislocation of the L3 vertebral body. Computed tomography angiography showed that the third lumbar artery was ruptured without active bleeding. The patient underwent posterior approach with reduction, transpedicular fixation, and posterolateral fusion with autologous bone graft. Finally, Vertebral reduction and sagittal balance were achieved and patients recovered well after operation. Preoperative blood vessel evaluation is very important to avoid massive bleeding during the surgery, and the standard technique which can achieve good reduction is easy to understand, perform, and is reproducible.


Preventing inhibition of tyrosinase with modified electrodes.
Wines, especially red wines, contain numerous biologically active compounds, the most important of which are polyphenols, whose nutritional importance is attributed to their antioxidant power. Because of this, the detection of the amount of phenolic compounds in red wines becomes extremely important. However, using free enzyme in the determination of phenolic compounds in wines cannot reflect the actual values since there are also naturally found inhibitors in red wines. In this study, benzoic acid, cinnamic acid, and sorbic acid were utilized to understand the behavior of immobilized polyphenol oxidase in the conducting polymer matrices toward inhibition. Cinnamic acid was found to be the most powerful inhibitor for both free and immobilized enzyme in copolymer matrix of poly(terephthalic acid bis-(2-thiophen-3-yl-ethyl) ester) (PTATE) with polypyrrole (PPy). In the case of immobilized enzyme in PPy matrix, it was observed that sorbic acid is a stronger inhibitor than cinnamic acid. The inhibitory effects of these inhibitors on PPO were compared with respect to both the structural differences of inhibitors and conducting polymer matrices.


Best behaviour: A proposal for a non-binary conceptualization of behaviour in biology.
Behaviour is a widespread object of research in biology, yet it is often left undefined, and the variety of existing definitions have not led to a consensus. We argue that the fundamental problem in defining behaviour has been the assumption that the concept must be categorical: either a phenomenon is a behaviour or it is not. We propose instead that 'behaviour' is best understood as a spectrum concept. We have identified three major characteristics of phenomena which, we argue, fuel the intuitions of biologists regarding the classification of cases as behaviour. All are related to the mechanistic explanations put forth to account for the phenomena, and are (i) the complexity of the mechanism, (ii) the stability of the constitutive entities, and (iii) the quantity and significance of the inputs to the underlying mechanism. We illustrate this new conceptualisation through a three-dimensional behaviour-space which highlights the apparently different conceptualizations of behaviour attributed to humans, animals and plants, showing that they, in fact, all partake of a unified, malleable understanding of a single concept.


Selective lumbar epidural block in labour. A clinical analysis.
Segmental epidural analgesia (T10-T12) was performed in 418 parturients, using a 4-6 ml dose of 0.5% bupivacaine, with or without adrenaline. Seventy per cent of parturients were primiparas and 30% had histories, or signs, of possible uteroplacental insufficiency. Our aim was to relieve pain during the long passive opening phase, so that mothers would be rested and active at the beginning of the second phase, but also to avoid abolishing the bearing-down reflex, the absence of which causes an increased frequency of instrumental delivery. The analgesia during the opening phase was of good quality in 89% of primiparas, and 84% of multiparas. The onset of analgesia was rapid (3-5 min) and the duration was on average 2 1/2 h. The incidence of foetal heart rate changes, during the 30 min after epidural, was 5%. The second phase was less than 30 min in about 90% of cases. About 90% of parturients delivered spontaneously, and the frequency of instrument delivery was only 7.4%. Caesarean section was required in 3.7%. Slight, but rapidly correctable, hypotension occurred in 16.5%, and in two cases the hypotension led to more serious complications. This stresses the importance of the availability and competence of both the anaesthetic and obstetric teams. There were no maternal or neonatal mortalities, and the Apgar scores compared well with the figures for the normal material in our obstetric unit.


[Expert dialogue: neuroendocrine tumours of the lungs and gastroenteropancreatic system].
Neuroendocrine tumours of the lung exhibit an increasing incidence and prevalence. However, data on the diagnosis of and therapy for these tumours are sparse compared to neuroendocrine tumours of the gastroenteropancreatic system. The present article reflects a dialogue between experts on neuroendocrine tumors of the lung and the gastroenteropancreatic system held on February 25th and 26th in Weimar, Germany. Many similarities exist between neuroendocrine tumours of the lung and the gastroenteropancreatic system but there are also significant differences. Similarities exist mainly concerning pathology, diagnosis and therapy. Differences exist regarding the systemic therapy and the significantly lower incidence of paraneoplastic syndromes. Somatostatin receptor PET/CT with gallium-68 labelled somatostatin analogues and peptide receptor radiotherapy are innovative methods for the diagnosis of and therapy for neuroendocrine tumours of the lung. The first treatment option remains complete resection of the tumour. Small molecules like everolimus (Afinitor®) have been tested in clinical trials and have been shown to prolong progression-free survival. Additional studies are necessary and efforts should be undertaken to establish a registry to increase data on methods suitable for he diagnosis of and therapy for neuroendocrine tumours of the lung.


Social class and social mobility--effects on survival. A study of an entire birth cohort during an 80-year life span.
The survival of all individuals living within a limited area (N = 489), born in 1902 and 1903, were studied from birth until 80 years of age according to parents' social class, own social class, and occupational mobility. There were no statistical significant differences in survival according to parents' social class. Bivariate survival analysis between 20-80 years of age, based on own social class, shown no significant differences. Concerning social mobility, when males and females were analyzed separately, those men with no mobility had a significantly lower survival rate than those with downward or upward mobility. For women there was no such difference in survival. In a multivariate survival analysis among eight social factors, sex and marital status had the greatest effect on survival between 20-80 years of age. Widows and widowers had, unexpectedly, a higher survival compared to married and never married persons.


A 5-year randomized controlled study of learning, problem solving ability, and quality of life modifications in people with type 2 diabetes managed by group care.
To study time course changes in knowledge, problem solving ability, and quality of life in patients with type 2 diabetes managed by group compared with individual care and education. We conducted a 5-year randomized controlled clinical trial of continuing systemic education delivered by group versus individual diabetes care in a hospital-based secondary care diabetes unit. There were 120 patients with non-insulin-treated type 2 diabetes enrolled and randomly allocated to group or individual care. Eight did not start and 28 did not complete the study. The main outcome measures were knowledge of diabetes, problem solving ability, quality of life, HbA1c, BMI, and HDL cholesterol. Knowledge of diabetes and problem solving ability improved from year 1 with group care and worsened among control subjects (P<0.001 for both). Quality of life improved from year 2 with group care but worsened with individual care (P<0.001). HbA1c level progressively increased over 5 years among control subjects (+1.7%, 95% CI 1.1-2.2) but not group care patients (+0.1%, -0.5 to 0.4), in whom BMI decreased (-1.4, -2.0 to -0.7) and HDL cholesterol increased (+0.14 mmol/l, 0.07-0.22). Adults with type 2 diabetes can acquire specific knowledge and conscious behaviors if exposed to educational procedures and settings tailored to their needs. Traditional one-to-one care, although delivered according to optimized criteria, is associated with progressive deterioration of knowledge, problem solving ability, and quality of life. Better cognitive and psychosocial results are associated with more favorable clinical outcomes.


Postmortem stability of RNA isolated from bovine reproductive tissues.
Molecular biology is being increasingly used to address the complex problem of bovine infertility. One common concern shared by many of these studies is the postmortem delay in obtaining reproductive tissues and the effect this may have on RNA dependent studies. To address this concern, bovine ovarian, oviduct and uterine tissue samples, collected over intervals ranging from 0 to 96 h postmortem to freeze storage, were analysed to determine the potential effects on RNA quantity and quality. The analysis showed that total RNA yields were not changed significantly by postmortem interval up to 96 h while 28S ribosomal RNA remained intact up to 24 h postmortem. Specific messenger RNA transcripts encoding beta-actin, GAPDH and transforming growth factor-beta were detected in all tissues up to 96 h postmortem using reverse transcriptase-polymerase chain reaction and Northern analysis indicated no detectable mRNA degradation up to 24 h postmortem. Finally, using poly(A)(+) mRNA isolated from ovarian tissues frozen 2 h postmortem, we constructed corpus luteum and ovarian cortex cDNA libraries containing 7.65x10(4) and 1.9x10(6) primary transformants with average cDNA lengths of 2.3 and 1.6 kb respectively. Taken together, these data show that a postmortem delay of up to 24 h does not significantly affect the yield or quality of RNA prepared from bovine reproductive tissues.