Time perception and affective disorders.
The estimation of short-time intervals by 60 control subjects and 56 patients with affective disorders was investigated using the three different methods of metronome adjustment, verbal estimation, and operative estimation (production). The patients were diagnosed according to DSM-III criteria. A group with major depression with melancholia (9), and another group with bipolar depression (8), tended to under-estimate time to about the same extent. A group with manic or hypomanic disorders (11) tended to over-estimate. Patients with major depression without melancholia (9), bipolar disorders in remission (9), and dysthymic disorders (10), had no decided tendencies to under- or over-estimate short time intervals. The estimation of longer intervals (5-10 min.) was not significantly altered in the patient groups. The results are discussed in the context of earlier investigations, which mainly have yielded no changes in ability to estimate time intervals despite a subjective feeling that time is passing slowly or quickly in affective disorders.


Enzymic properties of different types of human erythrocyte glucose-6-phosphate dehydrogenase, with characterization of two new genetic variants.
Enzymic properties have been compared in the following five genetic variants of glucose-6-phosphate dehydrogenase from human erythrocytes: the two common variants with normal activity, A and B; the common variant associated with enzyme deficiency, A-; and two new rare variants, "Ijebu-Ode" and "Ita-Bale."The maximal velocity of the enzyme reaction (V(max)) increases steadily with pH over the entire range explored (from pH 5.5 to 9.5) for all enzyme variants when buffers are used that show no specific ion effects on enzyme activity. Small differences are found among the variants in the pH range 7.5-8.2, where A and B show a "peak and trough," while A-, "Ijebu-Ode," and "Ita-Bale" exhibit a plateau. When the effects of reagents that bind to sulphydryl groups are compared, iodoacetate, bromoacetate, and iodoacetamide are weak inhibitors, while N-ethylmaleimide (NEM) and hydroxymercuribenzoate (HMB) are potent inhibitors. The last two reagents have differential inhibitory action on different variants; one of these, "Ijebu-Ode," is strikingly resistant to HMB and totally resistant to NEM (up to 3 mmoles/liter). The enzyme inactivation as a function of temperature exhibits distinctive profiles for all variants examined. BOTH OF THE NEW VARIANTS DESCRIBED DIFFER SIGNIFICANTLY FROM THE NORMAL B TYPE IN SEVERAL RESPECTS: "Ijebu-Ode" in electrophoretic mobility, thermostability, dependence of V(max) on pH, and resistance to sulphydryl group reagents; "Ita-Bale" in electrophoretic mobility, Michaelis constant (K(m)) for glucose-6-phosphate, and dependence of V(max) on pH. When these data are compared with those available in the literature, both variants are different from all those previously described. The estimated frequencies of the corresponding genes in western Nigeria are between 0.0005 and 0.0025 for "Ijebu-Ode" and less than 0.0005 for "Ita-Bale". The A- variant, compared to A, has a distinctly higher K(m) for 2-deoxyglucose-6-phosphate and is more inhibited by very low concentrations of HMB. These are the first observed differences in kinetic properties between A and A-.


[Chronic Reno-Cardial Continuum in Glomerulonephritis].
To elucidate main risk factors contributing to development of cardiovascular pathology at the predialysis stage of chronic glomerulonephritis. We examined 173 patients (90 men, 83 women, age 15-70, mean age 36.8+/-12.9 years) at predialysis stage of chronic glomerulonephritis. Cardiovascular pathology (coronary heart disease, disturbances of cardiac rhythm, left ventricular hypertrophy, chronic heart failure) was found in 88 patients. Clinical examination included history taking, physical examination with measurement of blood pressure BP and anthropological parameters, laboratory and instrumental investigation for diagnosis verification. Biochemical parameters studied were blood serum levels of cholesterol (Ch), high-density lipoprotein Ch, low-density lipoprotein Ch, fibrinogen, C-reactive protein, total protein, and creatinine. ECG and echocardiography were also performed. Presence of cardiovascular pathology was associated with higher concentration of calcium in blood serum (1.7+/-0.6 vs. 1.4+/-0.5 mmol/l, p<0.05), anemia with lower hemoglobin content, number and volume of erythrocytes, higher creatinine (150 [76-179]) vs. 100 [70-117] mcmol/l; p<0.05) and lower glomerular filtration rate (GFR) (80 [41-104] vs. 100 [69-122] ml/min; p<0.05). Main factors, contributing to development of cardiovascular pathology in patients at the predialysis stage of chronic glomerulonephritis were anemia, hypercalcemia, and lowering of GFR with increased serum creatinine.


Isoaspartyl dipeptidase activity of plant-type asparaginases.
Recombinant plant-type asparaginases from the cyanobacteria Synechocystis sp. PCC (Pasteur culture collection) 6803 and Anabaena sp. PCC 7120, from Escherichia coli and from the plant Arabidopsis thaliana were expressed in E. coli with either an N-terminal or a C-terminal His tag, and purified. Although each of the four enzymes is encoded by a single gene, their mature forms consist of two protein subunits that are generated by autoproteolytic cleavage of the primary translation products at the Gly-Thr bond within the sequence GTI/VG. The enzymes not only deamidated asparagine but also hydrolysed a range of isoaspartyl dipeptides. As various isoaspartyl peptides are known to arise from proteolytic degradation of post-translationally altered proteins containing isoaspartyl residues, and from depolymerization of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin), plant-type asparaginases may not only function in asparagine catabolism but also in the final steps of protein and cyanophycin degradation. The properties of these enzymes are compared with those of the sequence-related glycosylasparaginases.


Orofacial Myofunctional Therapy in Tongue Thrust Habit: A Narrative Review.
The respective review article is to provide an overview of the various exercises in orofacial myofunctional therapy (OMT) as a treatment modality for tongue thrust habit. Tongue thrust is the persistence of an infantile swallow pattern during late childhood. This leads to breathing and speech difficulties, open bite, and protruded teeth. During formative years, most children successfully transition from an infantile to a mature swallowing pattern. However, a few develop a retained infantile swallow and tongue thrust habit which could be due to abnormal habit like thumb sucking or an underlying cause like enlarged adenoids. Adverse effects of these habits can be avoided by early detection and intervention in a growing child. Tongue thrust can be treated in different ways with early diagnosis, removal of underlying causes, correcting tongue posture, and breaking of habit with the use of orthodontic appliances. This review article is focused on the various OMT techniques employed for the correction of tongue thrust. There are several exercises in OMT which can help a child with tongue thrust. These can be performed at home under the supervision of the child's parents. Orofacial myofunctional therapy has provided a dramatic and positive influence on patients treated for tongue thrust. The joy of eating, speaking, and correct breathing can be regained along with confidence, self-esteem, and improved quality of life. Clinically, OMT plays a positive role by not only improving swallow but also the posture of tongue, improper muscle function, and reduces relapse of previous orthodontic treatments. Shah SS, Nankar MY, Bendgude VD, et al. Orofacial Myofunctional Therapy in Tongue Thrust Habit: A Narrative Review. Int J Clin Pediatr Dent 2021;14(2):298-303.


The Abundant Histone Chaperones Spt6 and FACT Collaborate to Assemble, Inspect, and Maintain Chromatin Structure in Saccharomyces cerevisiae.
Saccharomyces cerevisiae Spt6 protein is a conserved chromatin factor with several distinct functional domains, including a natively unstructured 30-residue N-terminal region that binds competitively with Spn1 or nucleosomes. To uncover physiological roles of these interactions, we isolated histone mutations that suppress defects caused by weakening Spt6:Spn1 binding with the spt6-F249K mutation. The strongest suppressor was H2A-N39K, which perturbs the point of contact between the two H2A-H2B dimers in an assembled nucleosome. Substantial suppression also was observed when the H2A-H2B interface with H3-H4 was altered, and many members of this class of mutations also suppressed a defect in another essential histone chaperone, FACT. Spt6 is best known as an H3-H4 chaperone, but we found that it binds with similar affinity to H2A-H2B or H3-H4. Like FACT, Spt6 is therefore capable of binding each of the individual components of a nucleosome, but unlike FACT, Spt6 did not produce endonuclease-sensitive reorganized nucleosomes and did not displace H2A-H2B dimers from nucleosomes. Spt6 and FACT therefore have distinct activities, but defects can be suppressed by overlapping histone mutations. We also found that Spt6 and FACT together are nearly as abundant as nucleosomes, with ∼24,000 Spt6 molecules, ∼42,000 FACT molecules, and ∼75,000 nucleosomes per cell. Histone mutations that destabilize interfaces within nucleosomes therefore reveal multiple spatial regions that have both common and distinct roles in the functions of these two essential and abundant histone chaperones. We discuss these observations in terms of different potential roles for chaperones in both promoting the assembly of nucleosomes and monitoring their quality.


Interaction of copper (II) complexes by bovine serum albumin: spectroscopic and calorimetric insights.
Serum albumins being the most abundant proteins in the blood and cerebrospinal fluid are significant carriers of essential transition metal ions in the human body. Studies of copper (II) complexes have gained attention because of their potential applications in synthetic, biological, and industrial processes. Study of binding interactions of such bioinorganic complexes with serum albumins improves our understanding of biomolecular recognition process essential for rational drug design. In the present investigation, we have applied quantitative approach to explore interactions of novel synthesized copper (II) complexes viz. [Cu(L1)(L2)ClO4] (complex I), [Cu(L2)(L3)]ClO4] (complex II) and [Cu(L4)2(H2O)2] (complex III) with bovine serum albumin (BSA) to evaluate their binding characteristics, site and mode of interaction. The fluorescence quenching of BSA initiated by complexation has been observed to be static in nature. The binding interactions are endothermic driven by entropic factors as confirmed by high sensitivity isothermal titration calorimetry. Changes in secondary and tertiary structure of protein have been studied by circular dichroism and significant reduction in α-helical content of BSA was observed upon binding. Site marking experiments with warfarin and ibuprofen indicated that copper complexes bind at site II of the protein.


Small dense low-density lipoproteins and associated risk factors in patients with stroke.
Low-density lipoproteins (LDL) are a heterogeneous group of particles, with small, dense particles being more atherogenic. It remains controversial whether elevated plasma levels of small dense LDL (sd-LDL) are risk factors for stroke. The aim of the present study was to examine the plasma levels of sd-LDL in patients with stroke and to investigate the associations in a large Chinese case-control study. We recruited 299 stroke patients (159 cerebral thrombosis, 42 lacunar infarction, 98 intracerebral hemorrhage) and 299 controls. The semiquantitative analysis of plasma levels of sd-LDL was performed by nondenaturing gradient gel electrophoresis. (1) The plasma levels of sd-LDL in patients with ischemic stroke or hemorrhagic stroke were higher than in controls. (2) Multiple regression analysis showed that there were significant relationships between sd-LDL and triglyceride, high-density lipoprotein cholesterol, LDL cholesterol, systolic blood pressure and history of diabetes, and a significant relationship between sd-LDL and stroke (r = 0.286, p < 0.001) even after adjusting for these factors. (3) Compared with the controls, the calculation of odds ratios indicated relative risk estimates of 3.111 for ischemic stroke (OR = 3.111 , 95% CI = 1.891-5.117, p < 0.001) and 3.164 for hemorrhagic stroke (OR = 3.164, 95% CI = 1.632-6.137, p < 0.01). Plasma sd-LDL was independently associated with both thrombotic and hemorrhagic stroke, suggesting it may be an independent predictor of as well as a risk factor for stroke in Chinese people, justifying clinical trials for primary and secondary prevention of stroke using statins or fibrates.


Automatic Modulation Classification Based on Deep Learning for Unmanned Aerial Vehicles.
Deep learning has recently attracted much attention due to its excellent performance in processing audio, image, and video data. However, few studies are devoted to the field of automatic modulation classification (AMC). It is one of the most well-known research topics in communication signal recognition and remains challenging for traditional methods due to complex disturbance from other sources. This paper proposes a heterogeneous deep model fusion (HDMF) method to solve the problem in a unified framework. The contributions include the following: (1) a convolutional neural network (CNN) and long short-term memory (LSTM) are combined by two different ways without prior knowledge involved; (2) a large database, including eleven types of single-carrier modulation signals with various noises as well as a fading channel, is collected with various signal-to-noise ratios (SNRs) based on a real geographical environment; and (3) experimental results demonstrate that HDMF is very capable of coping with the AMC problem, and achieves much better performance when compared with the independent network.


Assessing cancer clinical trials: will your patient benefit from a 'breakthrough'?
Cancer patients and their families often ask their primary care physicians if a new treatment reported in the news can help them. Physicians familiar with the long and complicated process of oncologic clinical trials are in the best position to assess the potential for clinical benefit from a new antineoplastic therapy.


Longitudinal Relationships Between Help-Seeking Intentions and Depressive Symptoms in Adolescents.
Cross-sectional studies have shown an association between lower help-seeking intentions and greater depressive symptoms among adolescents. However, no longitudinal study has examined the direction of this association. The current study investigated whether help-seeking intentions and depressive symptoms are reciprocally associated at the within-person (individual) level during early to mid-adolescence. Longitudinal data on help-seeking intentions and depressive symptoms in adolescents were obtained from a population-based birth cohort study (Tokyo Teen Cohort; N = 3,171) at four time points (10y, 12y, 14y, and 16y). A random intercept cross-lagged panel model was used to evaluate the within-person prospective associations between help-seeking intentions and depressive symptoms. At the within-person level, significant associations were consistently observed between antecedent greater depressive symptoms and subsequent lower help-seeking intentions across all time points (10y-12y: standardized regression coefficient (β) = -0.12, p < .001; 12y-14y: β = -0.07, p < .05; and 14y-16y: β = -0.09, p < .01). Meanwhile, significant within-person associations were partly observed between antecedent lower help-seeking intentions and subsequent greater depressive symptoms from 10y to 12y (β = -0.07, p < .05) and from 14y to 16y (β = -0.12, p < .001). These prospective associations were almost the same when adjusted for the number of potential confidants as a time-varying confounder. Adolescents with worsening depressive symptoms may become increasingly reluctant to seek help over time. Proactive early recognition and intervention with support from parents, teachers, and other individuals may facilitate the management of depression in adolescents.


Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis.
Recent studies have revealed that TAK1 kinase is an essential intermediate in several innate immune signaling pathways. In this study, we investigated the role of TAK1 signaling in maintaining intestinal homeostasis by generating enterocyte-specific constitutive and inducible gene-deleted TAK1 mice. We found that enterocyte-specific constitutive TAK1-deleted mice spontaneously developed intestinal inflammation as observed by histological analysis and enhanced expression of IL-1beta, MIP-2, and IL-6 around the time of birth, which was accompanied by significant enterocyte apoptosis. When TAK1 was deleted in the intestinal epithelium of 4-wk-old mice using an inducible knockout system, enterocytes underwent apoptosis and intestinal inflammation developed within 2-3 days following the initiation of gene deletion. We found that enterocyte apoptosis and intestinal inflammation were strongly attenuated when enterocyte-specific constitutive TAK1-deleted mice were crossed to TNF receptor 1(-/-) mice. However, these mice later (>14 days) developed ileitis and colitis. Thus, TAK1 signaling in enterocytes is essential for preventing TNF-dependent epithelium apoptosis and the TNF-independent development of ileitis and colitis. We propose that aberration in TAK1 signaling might disrupt intestinal homeostasis and favor the development of inflammatory disease.


Immunocytochemical study of gastro-entero-pancreatic (GEP) endocrine cells in the vampire bat (Desmodos rotundus).
The distribution and frequency of gastro-entero-pancreatic (GEP) endocrine cells were studied in vampire bats by immunocytochemistry. Moderate numbers of somatostatin- and a few 5-hydroxytryptamine (5-HT)- and glucagon-immunoreactive cells were seen in the fundic cecum of the stomach. Numerous gastrin- and moderate numbers of somatostatin- and 5-HT-immunoreactive cells were found in the pyloric region. Moderate numbers of 5-HT-, somatostatin-, and gastrin-immunoreactive cells also were found in BRUNNER's glands. In addition to the above-mentioned 4 immunoreactive cell types, cells immunoreactive for glicentin, secretin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), and neurotensin were found in the intestine. Numerous insulin-, moderate numbers of somatostatin- and glucagon-, and a few 5-HT-immunoreactive cells were detected in the pancreatic islets with lesser numbers scattered within the exocrine pancreas. Motilin- and pancreatic polypeptide-immunoreactive cells were not observed in this study.


Melatonin for sleep problems in children with neurodevelopmental disorders.
Children with neurodevelopmental disorders are at risk of sleep problems, typically difficulty getting to sleep, sleep/wake rhythm disturbances and reduced duration of sleep (insomnia). This may be associated with abnormally timed or inadequate secretion of melatonin, a naturally-occurring hormone involved in coordinating the body's sleep-wake cycle. Previously, we reviewed the use of a melatonin product licensed for primary insomnia in adults aged over 55 years. Here we review off-label and unlicensed use of melatonin in children with attention-deficit hyperactivity disorder (ADHD) or autism spectrum disorder or related neurodevelopmental disorders.


[Intra-atrial conduction disorders of 2d degree].
Five patients with second degree intraatrial block are presented. The first three cases had a sick sinus syndrome with sinus bradycardia, broad P waves and episodes of atrial flutter or fibrillation. In these patients a Wenckebach phenomenon could bei elicited by atrial stimulation at a critical driving rate between the stimulated site and the recording electrode. In the first patient this conduction disturbance was obtained at several right atrial stimulation sites. The block could be elicited in the other two patients only in a limited area of the right atrium respectively only by left atrial pacing. In the remaining two patients an atrial tachycardia with block was observed. The intraatrial conduction disturbance was manifested as an exit block around the ectopic pacemaker. In one patient the tachycardia was induced by digitalis intoxication. In the other patient no etiologic factor of the tachycardia could be found. While the first three patients presented intraatrial conduction disturbances already in sinus rhythm, the last two cases showed after recovery from the atrial tachycardia P waves of normal duration and configuration.


Neutral noble gas compounds exhibiting a Xe-Xe bond: structure, stability and bonding situation.
The structure and stability towards decomposition of eight novel noble gas compounds having a Xe-Xe bond, which have not been experimentally observed so far, have been studied computationally. In addition, the nature of the Xe-Xe interaction has been analysed by a combination of the most popular methods to study the bonding situation of molecules, i.e. Natural Bond Orbital, Atom in Molecules and Energy Decomposition Analysis methods. Two related series of compounds have been considered: HXeXeX (X = F to I) and RXeXeR' (R = halogen atom). Our calculations indicate that the replacement of the fluorine atom by a heavier group 17 congener in the HXeXeX series leads to a less stable compound, thus making more difficult its experimental observation. The same effect occurs in the RXeXeR' series, but these species are more kinetically protected against the decomposition reaction and therefore, their experimental detection is more likely.


Design and evaluation of quasi-Nyquist WDM networks utilizing widely deployed wavelength-selective switches.
Photonic networks based on wavelength-selective switches (WSSs) can transport wavelength-division-multiplexed (WDM) signals in a cost-effective manner. To accommodate the ever-increasing network traffic, the spectral efficiency should be maximized by minimizing the bandwidth of the guardbands inserted between WDM signals. Quasi-Nyquist WDM systems are seen as offering the highest spectral efficiency in a feasible way. However, highly dense WDM systems suffer from the signal-spectrum narrowing induced by the non-rectangular passbands of WSSs. Furthermore, widely deployed WSSs cannot process quasi-Nyquist WDM signals since the signal-alignment granularity does not match the passband resolution of the WSSs. This paper proposes a network architecture that enables quasi-Nyquist WDM networking with widely deployed WSSs. Through intensive network analyses based on computer simulations, we confirm that it has 30.8% higher spectral efficiency than conventional networks. Its feasibility is verified by transmission experiments on 72-channel 32-Gbaud/400-Gbps dual-carrier dual-polarization 16-ary quadrature-amplitude-modulation signals aligned with 66.6-GHz spacing in the full C-band. The net fiber capacity of 28.8 Tbps, the transmission distance of 900 km, and the hop count of 9 are attained by our proposed quasi-Nyquist WDM networking scheme.


Use of a homemade nylon loop for the prevention of postpolypectomy bleeding of large pedunculated polyps.
To avoid bleeding after colonoscopic polypectomy, several procedures are being used. We describe a new method that consists of a homemade nylon loop that is applied and tied to the stalk of the pedunculated polyp and after which a conventional polypectomy is done. We have used this method in 15 patients and no complication was observed. The procedure is simple; the loop may be opened to large diameters to make it easier to use for large polyps. It has a low cost and seems to be safe and effective to prevent bleeding after endoscopic polypectomy.


Reflections on love's spirals.
This article seeks to explore how the experience of love and its expression might inform and guide reflection and inquiry into love. Despite the importance of love in our personal and professional lives, it remains a topic that has further scope for inquiry within nursing circles. The article takes as its catalyst an encounter that emerged out of a piece of research that was exploring individuals' experiences of becoming healers and the journey they undertook. One participant spoke deeply and profoundly of his experience of love, which generated for me a personal, experiential, and intellectual process of inquiry. The article seeks to try and create a synthesis between rational inquiry and subjective experience. It explores W. B. Yeats's notion of a gyre, a spiral, as an image and metaphor for integrating different conceptions and understandings of love. It seeks to illustrate how a more integrated understanding of love may open up spaces of inquiry that are more flexible, creative, and spontaneous.


Trends in the mortality of non-traumatic subarachnoid hemorrhage in Colombia: a 10-year analysis of a nationwide registry.
To assess trends in mortality from 1999 to 2008 resulting from non-traumatic subarachnoid hemorrhage (SAH) in the Colombian population. This population-based study analyzed all deaths by assuming a Poisson model. Subarachnoid hemorrhage-related deaths showed a statistically significant increase of 1.6% per year (p<0.001). The age-standardized analysis demonstrated an increased mortality trend of 3.3% per year (p<0.001) in people older than 70 years, but a decreased mortality trend in people younger than 50. It remained stable in patients 50-69 years old. The overall SAH-related mortality rate in Colombia has increased because increased mortality among the elderly has been counterbalanced by reduced mortality rates in younger age groups. These disparities may reflect epidemiologic transition, treatment inequities, or a less favorable comorbid profile.


Spontaneous internal hemorrhage of a giant hepatic hemangioma: A case report.
Hepatic hemangioma, a benign liver tumor, can rarely spontaneously rupture and hemorrhage, which is then associated with significant mortality. The diagnosis of internal hemorrhage is challenging and the management is disputed. We describe the case of a 52-year-old female patient with chief complaints of fever and anemia, with no history of recent trauma. Ultrasound suggested the possibility of a liver abscess and computed tomography (CT) examination revealed a giant space occupying lesion (SOL) (approximately 16 cm) in the right hepatic lobe, indicating a hepatic tumor or abscess. The patient did not respond to antibiotics and blood transfusion. Liver needle biopsy revealed blood clots suggestive of intratumoral hemorrhage, possibly of a hepatic hemangioma. Interventional radiologic approach revealed active bleeding at the phrenic artery that supplied the liver SOL. Thus, embolization was performed and re-angiography showed no active bleeding from the embolized vessel. The patient became afebrile, but fever recurred the next day. Hence, an exploratory open right hemihepatectomy was undertaken and the intraoperative frozen biopsy confirmed hepatic hemangioma with internal hemorrhage, but malignancy could not be excluded for some focal tissues. Postoperative pathology report confirmed the diagnosis of hepatic hemangioma with internal hemorrhage and excluded malignancy. The fever subsided and the patient was discharged in good health. A follow-up CT performed three months, postoperatively, indicated compensatory growth of the left hepatic lobe. This case demonstrates that the diagnosis of hepatic hemangioma with internal hemorrhage can be confirmed by needle biopsy and surgical resection is the optimal treatment for such a lesion.


[Chronic periodontitis with Takayasu arteritis: a case report].
This case report concerns a 23-year-old woman with chronic periodontitis who had been previously diagnosed with Takayasu arteritis (TA). Her erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level were decreased before and 3 months after non-surgical periodontal therapy with no change in her prescribed medications (ESR from 31.00 mm/h to 23.0 mm/h, CRP from 21.40 mg/L to 18.46 mm/h). Through the occasional findings, we raised a hypothetical analysis about the potential relationship between periodontitis and TA with respect to inflammatory factors, bacteria and medication. Further studies of large samples are needed to verify the findings.


Heart Failure Syndrome With Preserved Ejection Fraction Is a Metabolic Cluster of Non-resolving Inflammation in Obesity.
Heart failure with preserved ejection fraction (HFpEF) is an emerging disease with signs of nonresolving inflammation, endothelial dysfunction, and multiorgan defects. Moreover, based on the clinical signs and symptoms and the rise of the obesity epidemic, the number of patients developing HFpEF is increasing. From recent molecular and cellular studies, it becomes evident that HFpEF is not a single and homogenous disease but a cluster of heterogeneous pathophysiology with aging at the base of the pyramid. Obesity superimposed on aging drives the number of inflammatory pathways that intersect with metabolic dysfunction and suboptimal inflammation. Here, we compiled information on obesity-directed macrophage dysfunction that coincide with metabolic defects. Obesity-associated proinflammatory stimuli facilitates heart and interorgan inflammation in HFpEF. Furthermore, diversified mechanisms that drive heart failure urge the need of studying pervasive and unresolved inflammation in animal models to understand HFpEF. A broad and system-based approach will help to study major translational aspects of HFpEF, since no single animal model recapitulates all signs of differential HFpEF stages in the clinical setting. Here, we covered experimental models that target HFpEF and emphasized the advances observed with formyl peptide 2 (FPR2) receptor, a prime sensor that is important in inflammation-resolution signaling. Dysfunction of FPR2 led to the development of spontaneous obesity, impaired macrophage function, and triggered kidney fibrosis, providing evidence of multiorgan defects in HFpEF in an obesogenic aging experimental model.


Metabolic Resistance in Bed Bugs.
Blood-feeding insects have evolved resistance to various insecticides (organochlorines, pyrethroids, carbamates, etc.) through gene mutations and increased metabolism. Bed bugs (Cimex lectularius) are hematophagous ectoparasites that are poised to become one of the major pests in households throughout the United States. Currently, C. lectularius has attained a high global impact status due to its sudden and rampant resurgence. Resistance to pesticides is one factor implicated in this phenomenon. Although much emphasis has been placed on target sensitivity, little to no knowledge is available on the role of key metabolic players (e.g., cytochrome P450s and glutathione S-transferases) towards pesticide resistance in C. lectularius. In this review, we discuss different modes of resistance (target sensitivity, penetration resistance, behavioral resistance, and metabolic resistance) with more emphasis on metabolic resistance.


BMI but not stage or etiology of nonalcoholic liver disease affects the diagnostic utility of carbohydrate-deficient transferrin.
A reliable biomarker is required in hepatology clinics for detection and follow-up of heavy alcohol consumption. Carbohydrate-deficient transferrin (CDT) increases with sustained heavy alcohol consumption and is the most specific biomarker of ethanol (EtOH) consumption. Recent introduction of a standardized method for measuring CDT has improved its clinical application. This study was designed to determine whether alcohol-independent factors influence CDT levels in patients with chronic liver disease (CLD). The relationship between serum %CDT and self-reported history of alcohol consumption was examined in 254 patients referred for evaluation of liver disease. CDT analysis was performed on serum collected at time of liver biopsy. CDT levels were not affected by severity or etiology of nonalcoholic liver disease. Thirteen of 254 subjects had a %CDT >1.7, predictive of heavy alcohol intake, 6 of whom did not acknowledge heavy drinking. Twelve of these 13 subjects were suspected heavy drinkers on review of their medical records and clinical results. Conversely, not all acknowledged heavy drinkers had %CDT >1.7. Heavy drinkers with a body mass index (BMI) in the overweight or obese range had significantly lower %CDT than lean heavy drinkers. This persisted even when lean body weight was used as an approximation of the EtOH volume of distribution. An elevated BMI reduces the diagnostic utility of CDT at higher alcohol intake in subjects with CLD using the standardized method. In a hepatology outpatient setting, this assay is likely to be useful to confirm suspicion of heavy drinking in subjects who are not overweight, but cannot reliably identify moderate drinkers or heavy drinkers who are overweight.


[A comparative study of nitric oxide (NO) gas solution, L-arginine and D-arginine on superoxide anion radical generation using human polymorphonuclear leukocytes].
Nitric oxide (NO) has been studied from various aspects since NO had been recognized as an endothelium-derived relaxing factor (EDRF). We studied the effect of NO gas solution, L-arginine and D-arginine on superoxide anion radical (O2-) generation using human polymorphonuclear leukocytes by chemiluminescence method. NO gas solution inhibited O2- generation induced by fMLP or PMA in a dose-dependent fashion, whereas L-arginine that in NO precursor increased O2- generation. On the other hand, D-arginine which is an optical isomer, had no effect on O2- generation. These results suggest that L-arginine administered externally may be different from endogenous L-arginine and has a different effect on O2- generation. Therefore, we must pay attention to biological effects of L-arginine when experiments are performed on nitric oxide.


Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer.
CDC6 plays a critical role in regulation of the onset of DNA replication in eukaryotic cells. We have found that Cdc6 expression is down-regulated in prostate cancer as detected by semiquantitative reverse transcriptase-PCR of prostate cell lines and laser-captured microdissected prostate tissues. This result was substantiated by immunohistochemical analysis of paraffin-embedded tissue sections and immunoblot analysis of benign (BPH-1) and adenocarcinomatous prostatic cells. Furthermore, a 100-fold reduction in the transcription efficiency of the Cdc6 promoter-luciferase construct was noted in the metastatic PC3 cells compared with that in BPH-1 cells. Concentration of the E2F and Oct1 transcription factors that have putative binding sites in the Cdc6 promoter was substantially low in PC3 cells compared with BPH cells. Mutagenesis of the two E2F binding sites on the Cdc6 promoter resulted in increased promoter activity in PC3 cells owing to elimination of the negative regulation by pRb.E2F complex but not to the level of that obtained in BPH cells. We conclude that an altered interaction of transcription factors may be responsible for the down-regulation of Cdc6 transcription in PC3 cells. Our study suggests a potential use of the lack of CDC6 expression as an index of prostate cancer development.


Cyclic peptide therapeutics: past, present and future.
Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics. Over 40 cyclic peptide drugs are currently in clinical use and around one new cyclic peptide drug enters the market every year on average. The vast majority of clinically approved cyclic peptides are derived from natural products, such as antimicrobials or human peptide hormones. New powerful techniques based on rational design and in vitro evolution have enabled the de novo development of cyclic peptide ligands to targets for which nature does not offer solutions. A look at the cyclic peptides currently under clinical evaluation shows that several have been developed using such techniques. This new source for cyclic peptide ligands introduces a freshness to the field, and it is likely that de novo developed cyclic peptides will be in clinical use in the near future.


Australian bat lyssavirus infection in three fruit bats from north Queensland.
We report the case findings of Australian bat lyssavirus infection in two black flying foxes (Pteropus alecto) and one little red flying fox (Pteropus scapulatus) from north Queensland between January 1995 and August 1996. Although the P. alecto case in January 1995 is the first recognised case of Australian bat lyssavirus infection in Australia, this was a retrospective diagnosis made after identification of the index case at Ballina in May 1996. Eight persons had exposure to the three bats. Serum antibodies to classical rabies virus were measured in six of these persons; the only one seropositive was a veterinarian who had previously been vaccinated against rabies. Six persons received rabies vaccine following exposure. None of the in-contact humans developed signs of lyssavirus infection. For people exposed to Australian bat lyssavirus-positive bats who have not been scratched or bitten or had mucosal contamination by these bats, we suggest a post-exposure regime of five inoculations of the human diploid cell inactivated rabies vaccine.


A solitary cauliflower-like nodule on the mucosal surface of the lower lip.
The incidence of oral condylomata acuminata and simultaneous genital condylomata is not known. A review of the literature implies that the disease is rare, but it is more likely that it is only rarely reported. As the virus is autoinoculable and transmissible, the etiologic factor in this case of oral condylomata acuminatum is most likely orogenital contact. This case report serves as a reminder also that oroanogenital contact expands the anatomic range of sexually transmitted diseases.


Crosstalk of the Androgen Receptor with Transcriptional Collaborators: Potential Therapeutic Targets for Castration-Resistant Prostate Cancer.
Prostate cancer is the second leading cause of death from cancer among males in Western countries. It is also the most commonly diagnosed male cancer in Japan. The progression of prostate cancer is mainly influenced by androgens and the androgen receptor (AR). Androgen deprivation therapy is an established therapy for advanced prostate cancer; however, prostate cancers frequently develop resistance to low testosterone levels and progress to the fatal stage called castration-resistant prostate cancer (CRPC). Surprisingly, AR and the AR signaling pathway are still activated in most CRPC cases. To overcome this problem, abiraterone acetate and enzalutamide were introduced for the treatment of CRPC. Despite the impact of these drugs on prolonged survival, CRPC acquires further resistance to keep the AR pathway activated. Functional molecular studies have shown that some of the AR collaborative transcription factors (TFs), including octamer transcription factor (OCT1), GATA binding protein 2 (GATA2) and forkhead box A1 (FOXA1), still stimulate AR activity in the castration-resistant state. Therefore, elucidating the crosstalk between the AR and collaborative TFs on the AR pathway is critical for developing new strategies for the treatment of CRPC. Recently, many compounds targeting this pathway have been developed for treating CRPC. In this review, we summarize the AR signaling pathway in terms of AR collaborators and focus on pyrrole-imidazole (PI) polyamide as a candidate compound for the treatment of prostate cancer.


Discovery of an alpha-melanotropin antagonist effective in vivo.
A hybrid analogue, H-His-D-Arg-Ala-Trp-D-Phe-Lys-NH2, was designed based upon the primary structures of a growth hormone-releasing peptide analogue, [His1,Lys6]GHRP, and the MSH fragment, Ac-alpha-MSH(6-11)-NH2. In vitro studies demonstrated the alpha-MSH antagonistic efficacy of the analogue in the lizards Sceloporus jarrovii and Urosaurus ornatus. In live white background-adapted S. jarrovii previously injected with the antagonist (10 nmol/5 g b.wt.), maximal skin darkening induced by alpha-MSH was reduced to 50%. In white background-adapted U. ornatus, previous injection of the analogue (1 nmol/5 g b.wt.) totally abolished the response to alpha-MSH and depressed to 50% the maximal response elicited by the superpotent MSH analogue, [Nle4,D-Phe7]alpha-MSH.


[OPG and OPGL expression in condyle cartilage of temporomandibular joint following anterior disc displacement].
To investigate the change of osteoprotegerin (OPG) and OPGL expression and its significance in condylar cartilage after anterior disc displacement (ADD). Twenty healthy adult Japanese rabbits (from medical animal center of Zhejiang University) weighing from 2 to 3 kg were used in this study. Sixteen rabbits were subjected to surgical anterior disc displacement in the right temporomandibular joints (TMJ), four rabbits were sacrificed 1, 2, 4, 8 weeks post-operation,respectively; two rabbits with sham-operation and two without operation were as control. The structure of temporomandibular joint was observed under microscope. The expression of OPG and OPGL in condylar cartilage were examined by S-P immunohistochemical staining and measured with Image Computer Analysis Software. Date was statistically analyzed by one-way ANOVA. Experimental and sham-operative animals tolerated the surgical procedures well. The discs displaced anteriorly were observed in the surgical rabbits by general and microscope observation. The expression of OPG and OPGL was detected in the proliferating zone and hypertrophy zone cells of condyle in all animals. However, the expression of OPG and OPGL was stronger in the surgical group. There was significant difference in average gray degree (P<0.05) between the experimental and control groups. The ratio of OPG/OPGL was stable. The expression of OPG and OPGL in condylar cartilage was increased after ADD. They might play a role in the development and prognosis of the temporomandibular condylar cartilage alteration after ADD.


Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells.
Histone replacement by transition proteins (TPs) and protamines (Prms) constitutes an essential step for the successful production of functional male gametes, yet nothing is known on the underlying functional interplay between histones, TPs, and Prms. Here, by studying spermatogenesis in the absence of a spermatid-specific histone variant, H2A.L.2, we discover a fundamental mechanism involved in the transformation of nucleosomes into nucleoprotamines. H2A.L.2 is synthesized at the same time as TPs and enables their loading onto the nucleosomes. TPs do not displace histones but rather drive the recruitment and processing of Prms, which are themselves responsible for histone eviction. Altogether, the incorporation of H2A.L.2 initiates and orchestrates a series of successive transitional states that ultimately shift to the fully compacted genome of the mature spermatozoa. Hence, the current view of histone-to-nucleoprotamine transition should be revisited and include an additional step with H2A.L.2 assembly prior to the action of TPs and Prms.


Evaluation of the Family Liaison Officer role during the COVID-19 pandemic.
Communication within healthcare settings is often a subject of contention for patients' families at the best of times; however, contention was greatly magnified in the United Kingdom by restrictions on hospital visitations during the early stage of the COVID-19 pandemic. To support communication between families and patients, a central London hospital introduced the role of the family liaison officer (FLO). This study was designed to evaluate the rapid implementation of the FLO and to explore potential for it to become a standard role. Semi-structured interviews were conducted with five FLOs and seven colleagues who had worked alongside them between April and June, 2020. Two versions of the role emerged based on FLOs' previous background: clinical (primarily nurses) and pastoral (primarily play specialists). The FLO became a key role during the pandemic in facilitating communication between patients, clinical teams, and families. Challenges associated with the role reflect the speed in which it was implemented. It was evident to those in the role, and clinicians who the role was supporting, that it had potential to help improve hospital communication and the work of healthcare staff beyond the pandemic.


The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans.
In Caenorhabditis elegans, reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C. elegans ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of daf-2 and glp-1 mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, mbk-1 loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in daf-2 mutant animals. These findings indicate that mbk-1 and daf-16 functionally interact in the germline- but not in the daf-2 pathway. Together, our data suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.


Release of mediators from free bronchoalveolar cells: effect of ionophore A23187 and antigen challenge.
The ionophore A23187 stimulated the release of prostaglandins and SRS-A (now identified as leukotriene D4) from guinea-pig bronchoalveolar macrophages. Upon specific antigen challenge of the cells obtained from ovalbumin-sensitized animals or of normal cells preincubated with the serum of sensitized animals, prostaglandins, SRS-A or histamine were undetectable. Furthermore, treatment of "sensitized" cells with the ionophore resulted in a reduced liberation of prostaglandins in comparison to control cells. It is suggested that sensitization produce in bronchoalveolar macrophages some functional alterations of arachidonic acid oxygenation products.


Alterations of the miR-126-3p/POU2AF1/Spi-B Axis and JCPyV Reactivation in Multiple Sclerosis Patients Receiving Natalizumab.
Natalizumab (NTZ) can reactivate human polyomavirus John Cunningham polyomavirus (JCPyV) latent infection and lead to progressive multifocal leukoencephalopathy (PML). NTZ modulates the expression of microRNA-126-3p (miR-126-3p) and its target genes, Spi-B, POU2AF1, and vascular cell adhesion molecule-1 (VCAM-1); Spi-B protein binds the JCPyV regulatory region, initiating early gene transcription. This paper is aimed to evaluate the miR-126-3p and soluble (s)VCAM-1 concentration, Spi-B/POU2AF1 gene expression, and JCPyV activity in patients with multiple sclerosis (MS) before and during 2-years NTZ. Serum miR-126-3p and sVCAM-1 concentration was measured before NTZ and after 1, 12, and 24 months of treatment in 22 MS subjects, 1 patient who developed PML, and 29 healthy controls (HCs). The Spi-B and POU2AF1 expression in blood was analyzed at baseline and at month 24 in 13 patients with MS; results were clusterized based on JCPyV activity. miR-126-3p was significantly downregulated in MS before and during NTZ but was greatly increased in the PML patient. sVCAM-1 concentration was comparable in MS and HCs, and was reduced by NTZ in MS and PML. Spi-B/POU2AF1 expression was significantly increased in MS at baseline and was upregulated by NTZ, particularly in JCPyV-infected patients in whom JCPyV reactivation was detected. Taken together, the results suggest that the modulation of the miR-126-3p/POU2AF1/Spi-B axis associates with JCPyV activity in NTZ-treated patients with MS.


Cs3REIIIGe3O9 (RE = Pr, Nd, and Sm-Yb) and Cs8TbIII2TbIVGe9O27: A Rare Example of a Mixed-Valent Tb(III)/Tb(IV) Oxide.
Single crystals of 12 new cesium rare earth germanates crystallizing in two new structure types were grown from a CsCl/CsF flux. Cs3REGe3O9 (RE = Pr, Nd, and Sm-Yb), a new family of germanates that form for almost the entire series of rare earth elements, crystallizes in orthorhombic space group Pna21 with lattice parameters in the following ranges: a = 13.7033(4)-14.022(2) Å, b = 7.0545(2)-7.2405(12) Å, and c = 12.6672(4)-12.836(2) Å. Surprisingly, the Tb reaction yielded both Cs3TbGe3O9 and Cs8Tb3Ge9O27, a rare example of a mixed-valent Tb(III)/Tb(IV) compound. Cs8Tb3Ge9O27 crystallizes in space group P3 with the following lattice parameters: a = 11.2906(4) Å, and c = 7.9605(3) Å. The mixed-valent oxidation state of Tb was confirmed by structure solution, bond-valence sums, X-ray photoelectron spectroscopy data, and magnetic data. Optical and magnetic properties are reported for both sets of compounds.


A bioinformatics perspective on proteomics: data storage, analysis, and integration.
The field of proteomics is advancing rapidly as a result of powerful new technologies and proteomics experiments yield a vast and increasing amount of information. Data regarding protein occurrence, abundance, identity, sequence, structure, properties, and interactions need to be stored. Currently, a common standard has not yet been established and open access to results is needed for further development of robust analysis algorithms. Databases for proteomics will evolve from pure storage into knowledge resources, providing a repository for information (meta-data) which is mainly not stored in simple flat files. This review will shed light on recent steps towards the generation of a common standard in proteomics data storage and integration, but is not meant to be a comprehensive overview of all available databases and tools in the proteomics community.


A novel approach for chewing detection based on a wearable PPG sensor.
Monitoring of human eating behaviour has been attracting interest over the last few years, as a means to a healthy lifestyle, but also due to its association with serious health conditions, such as eating disorders and obesity. Use of self-reports and other non-automated means of monitoring have been found to be unreliable, compared to the use of wearable sensors. Various modalities have been reported, such as acoustic signal from ear-worn microphones, or signal from wearable strain sensors. In this work, we introduce a new sensor for the task of chewing detection, based on a novel photoplethysmography (PPG) sensor placed on the outer earlobe to perform the task. We also present a processing pipeline that includes two chewing detection algorithms from literature and one new algorithm, to process the captured PPG signal, and present their effectiveness. Experiments are performed on an annotated dataset recorded from 21 individuals, including more than 10 hours of eating and non-eating activities. Results show that the PPG sensor can be successfully used to support dietary monitoring.


Differences in adenosine triphosphate dependency of receptor-mediated endocytosis of alpha 2-macroglobulin and insulin correlate with separate routes of ligand-receptor complex internalization.
Biochemical and morphological studies compared the ATP requirements for and the internalization routes of alpha 2-macroglobulin and insulin in H35 hepatoma cells. Cellular ATP concentrations were decreased more than 94% by 1 mM 2,4-dinitrophenol or 10 mM sodium azide, potassium cyanide, or oligomycin. ATP depletion decreased total cell-associated alpha 2-macroglobulin 70-90% by inhibiting binding 67-77% and receptor-mediated internalization 90-96%. Under the same conditions, insulin binding was decreased less than 10%, and endocytosis and intracellular accumulation were not affected. Quantitative electron microscopic analysis of the distribution of occupied receptors on the surface of control and treated cells was performed using colloidal gold-labeled alpha 2-macroglobulin or insulin. alpha 2-Macroglobulin concentrated in and was internalized almost exclusively by coated pits. Insulin was rarely associated with coated pits, but was found in and internalized by noncoated invaginations. ATP depletion did not affect receptor mobility or ligand-induced aggregation of either receptor. There was an increase in the amount of alpha 2-macroglobulin found in coated pit-like structures. The coat underlying pits in ATP-depleted cells was poorly defined and may account for the inability of coated pits to form and/or internalize. These results showed that receptor-mediated internalization via coated pits was ATP dependent, whereas internalization via pinocytotic invaginations was energy independent, which explained the difference in the ATP dependency of uptake for the two ligands. These observations suggested that autophosphorylation of the insulin receptor may not be involved in either the aggregation or internalization of the insulin-receptor complex, since ATP depletion did not affect either process. This study provided evidence that specialized mechanisms exist for the internalization of insulin which may be related to some of its intracellular effects.


Smooth Muscle Stiffness Sensitivity is Driven by Soluble and Insoluble ECM Chemistry.
Smooth muscle cell (SMC) invasion into plaques and subsequent proliferation is a major factor in the progression of atherosclerosis. During disease progression, SMCs experience major changes in their microenvironment, such as what integrin-binding sites are exposed, the portfolio of soluble factors available, and the elasticity and modulus of the surrounding vessel wall. We have developed a hydrogel biomaterial platform to examine the combined effect of these changes on SMC phenotype. We were particularly interested in how the chemical microenvironment affected the ability of SMCs to sense and respond to modulus. To our surprise, we observed that integrin binding and soluble factors are major drivers of several critical SMC behaviors, such as motility, proliferation, invasion, and differentiation marker expression, and these factors modulated the effect of stiffness on proliferation and migration. Overall, modulus only modestly affected behaviors other than proliferation, relative to integrin binding and soluble factors. Surprisingly, pathological behaviors (proliferation, motility) are not inversely related to SMC marker expression, in direct conflict with previous studies on substrates coupled with single extracellular matrix (ECM) proteins. A high-throughput bead-based ELISA approach and inhibitor studies revealed that differentiation marker expression is mediated chiefly via focal adhesion kinase (FAK) signaling, and we propose that integrin binding and FAK drive the transition from a migratory to a proliferative phenotype. We emphasize the importance of increasing the complexity of in vitro testing platforms to capture these subtleties in cell phenotypes and signaling, in order to better recapitulate important features of in vivo disease and elucidate potential context-dependent therapeutic targets.


Microstructure of magnesium fluoride films deposited by boat evaporation at 193 nm.
Single layer magnesium fluoride (MgF2) was deposited on fused-silica substrates by a molybdenum boat evaporation process at 193 nm. The formation of various microstructures in relation to the different substrate temperatures and deposition rates were investigated. The relation between these microstructures (including cross-sectional morphology, surface roughness, and crystalline structures), the optical properties (including refractive index and optical loss) and stress, were all investigated. It was found that the laser-induced damage threshold (LIDT) would be affected by the microstructure, optical loss, and stress of the thin film. To obtain a larger LIDT value and better optical characteristics, MgF2 films should be deposited at a high substrate temperature (300 degrees C) and at a low deposition rate (0.05 nm s(-1)).


Physics, Structures, and Applications of Fluorite-Structured Ferroelectric Tunnel Junctions.
The interest in ferroelectric tunnel junctions (FTJ) has been revitalized by the discovery of ferroelectricity in fluorite-structured oxides such as HfO2 and ZrO2 . In terms of thickness scaling, CMOS compatibility, and 3D integration, these fluorite-structured FTJs provide a number of benefits over conventional perovskite-based FTJs. Here, recent developments involving all FTJ devices with fluorite structures are examined. The transport mechanism of fluorite-structured FTJs is explored and contrasted with perovskite-based FTJs and other 2-terminal resistive switching devices starting with the operation principle and essential parameters of the tunneling electroresistance effect. The applications of FTJs, such as neuromorphic devices, logic-in-memory, and physically unclonable function, are then discussed, along with several structural approaches to fluorite-structure FTJs. Finally, the materials and device integration difficulties related to fluorite-structure FTJ devices are reviewed. The purpose of this review is to outline the theories, physics, fabrication processes, applications, and current difficulties associated with fluorite-structure FTJs while also describing potential future possibilities for optimization.


Distinctive mucositis and feeding-tube dependency in cetuximab plus radiotherapy for head and neck cancer.
Prophylactic percutaneous endoscopic gastrostomy may be considered before chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma, because severe mucositis is a common complication. We evaluated the mucosal findings and necessity of prophylactic percutaneous endoscopic gastrostomy in patients with head and neck squamous cell carcinoma receiving cetuximab and radiotherapy. Fourteen consecutive patients with locally advanced head and neck squamous cell carcinoma receiving cetuximab and radiotherapy were analyzed. Patients' backgrounds were as follows: male/female, 8/6; median age, 64.5 years (range, 35-83 years); performance status, 0/1, 9/5. Primary tumor sites included the oropharynx, hypopharynx and larynx in four, seven and three patients, respectively. Patients completed a median of eight cetuximab cycles. All patients received three-dimensional conformal radiotherapy (median dose, 70 Gy). Thirteen patients were treated with elective neck irradiation at the ipsilateral (n = 3) or bilateral (n = 10) nodes. Grade ≥ 3 mucositis/stomatitis (clinical examination) occurred in 85.7% patients (n = 12). The median irradiation dose was 33 Gy at the Grade 3 mucositis onset. Eight patients showed mucositis with distinctive features, a wide range of white-coated lesions with a clear border; hypopharyngeal atresia was observed in two patients. Prophylactic percutaneous endoscopic gastrostomy was performed in 11 patients, and 11 patients (78.6%) actually required nutritional support because of Grade ≥ 3 mucositis/stomatitis (functional/symptomatic). Prophylactic percutaneous endoscopic gastrostomy is recommended because most patients receiving cetuximab and radiotherapy for locally advanced head and neck squamous cell carcinoma have Grade ≥ 3 mucositis with distinctive features.


Entropically driven Polymeric Enzyme Inhibitors by End-Group directed Conjugation.
A new generic concept for polymeric enzyme inhibitors is presented using the example of poly(2-methyl-2-oxazoline) (PMOx) terminated with an iminodiacetate (IDA) function. These polymers are shown to be non-competitive inhibitors for horseradish peroxidase (HRP). Mechanistic investigations revealed that the polymer is directed to the protein by its end group and collapses at the surface in an entropy-driven process as shown by isothermal titration calorimetry. The dissociation constant of the complex was determined as the inhibition constant Ki using HRP kinetic activity measurements. Additional experiments suggest that the polymer does not form a diffusion layer around the protein, but might inhibit by inducing minor conformational changes in the protein. This kind of inhibitor offers new avenues towards designing bioactive compounds.


Site-selective Synthesis of β-[70]PCBM-like Fullerenes: Efficient Application in Perovskite Solar Cells.
We report on the site-selective synthesis of PCBM-like [70]fullerene site-isomers, where the elusive β-site-isomers are, for the first time, the major product in a (cyclo)addition chemical reaction involving [70]fullerene. The reaction involves an straightforward cyclopropanation of [70]fullerene from sulfonium salts, affording a mixture of α and β site-isomers in good yields. Amazingly, the preference for the α- or β-site-isomer can be efficiently controlled by means of the solvent polarity! DFT theoretical calculations (DMF and toluene) nicely predict that, although the formation of the α-adduct is, as expected, thermodynamically favored, the selectivity of the process is determined by the energy difference of the respective transition states. Furthermore, the employ of α or/and β site-isomers, as pure materials or as a mixture of them, used as templating agent, has been evaluated in perovskite solar cells. The positive influence of the [70]fullerenes by passivating the voids/pin-holes and/or deep slits, is reflected in highly efficient and stable bulk heterojunction perovskite solar cells, whose performance (around 20 %) is slightly but consistently depending on the isomeric fullerene composition. These experimental findings pave the way to investigate a new reactivity on C70 and to explore the properties of the less-known β-derivatives.


Optimizing strategies to identify high risk of developing type 2 diabetes.
The success of diabetes prevention based on early treatment depends on high-quality screening. This study compared the diagnostic properties of currently recommended screening strategies against alternative score-based rules to identify those at high risk of developing diabetes. The study used data from ELSA-Brasil, a contemporary cohort followed up for a mean (standard deviation) of 7.4 (0.54) years, to develop risk functions with logistic regression to predict incident diabetes based on socioeconomic, lifestyle, clinical, and laboratory variables. We compared the predictive capacity of these functions against traditional pre-diabetes cutoffs of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), and glycated hemoglobin (HbA1c) alone or combined with recommended screening questionnaires. Presenting FPG > 100 mg/dl predicted 76.6% of future cases of diabetes in the cohort at the cost of labeling 40.6% of the sample as high risk. If FPG testing was performed only in those with a positive American Diabetes Association (ADA) questionnaire, labeling was reduced to 12.2%, but only 33% of future cases were identified. Scores using continuously expressed clinical and laboratory variables produced a better balance between detecting more cases and labeling fewer false positives. They consistently outperformed strategies based on categorical cutoffs. For example, a score composed of both clinical and laboratory data, calibrated to detect a risk of future diabetes ≥20%, predicted 54% of future diabetes cases, labeled only 15.3% as high risk, and, compared to the FPG ≥ 100 mg/dl strategy, nearly doubled the probability of future diabetes among screen positives. Currently recommended screening strategies are inferior to alternatives based on continuous clinical and laboratory variables.


Psychological assessment of children and adolescents with obesity.
Objective This study aimed to analyse the psychological conditions and behaviour of a group of Chinese children and adolescents with obesity, and to develop an intervention for these young patients. Methods A group of 72 patients aged from 4 to 15 years were recruited from an obesity clinic. Patients, or the parents of children younger than 12 years, filled out a series of self-report questionnaires, and the responses were recorded and analysed. Results The 72 children and adolescents with obesity had a mean age of 9.14 ± 2.18 years. The body mass index-z scores of children with obesity showed a significant positive correlation with the level of impulsive behaviour, motivational impulses, and cognitive instability (inattention). Children with obesity quickly responded with extreme emotions, and these responses were positively correlated with the degree of obesity (slight, intermediate, or severe obesity). Conclusion Children and adolescents being treated for obesity have many underlying psychological problems, including emotional instability and impulsivity, and are prone to extreme emotional-psychological problems. These difficulties are positively correlated with the degree of obesity. Therefore, clinical treatment of these problems requires not only use of medication, improved nutrition, and healthy exercise, but also addressing underlying psychologic problems.


Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers.
Acetaminophen (APAP) by oral or intravenous (iv) routes is used for mild to moderate pain but may take time to be effective. When fast relief is required and/or oral or iv routes are not available because of the patient's condition, the transmucosal route may be an alternative. A new transmucosal/buccal (b) pharmaceutical form of APAP dissolved in 50% wt alcohol is compared with other routes of administration. Two consecutive randomized, crossover, double-blind clinical trials (CT1: NCT00982215 and CT2: NCT01206985) included 16 healthy volunteers. CT1 compared the pharmacology of 250 mg bAPAP with 1 g iv APAP. CT2 compared the pharmacodynamics of 125 mg bAPAP with 1 g iv and 125 mg sublingual (s) APAP. Mechanical pain thresholds are recorded in response to mechanical stimuli applied on the forearm several times during 120 minutes. The objective is to compare the time of onset of antinociception and the antinociception (area under the curve) between the routes of administration with analysis of variance (significance P<0.05). bAPAP has a faster time of antinociception onset (15 minutes, P<0.01) and greater antinociception at 50 minutes (P<0.01, CT1) and 30 minutes (P<0.01, CT2) than ivAPAP and sAPAP. All routes are similar after 50 minutes. bAPAP has a faster antinociceptive action in healthy volunteers. This attractive alternative to other routes would be useful in situations where oral or iv routes are not available. This finding must now be confirmed in patients suffering from acute pain of mild and moderate intensity.


Hematopoietic stem cells undergo a lymphoid to myeloid switch in early stages of emergency granulopoiesis.
Emergency granulopoiesis is the enhanced and accelerated production of granulocytes that occurs during acute infection. The contribution of hematopoietic stem cells (HSCs) to this process was reported; however, how HSCs participate in emergency granulopoiesis remains elusive. Here, using a mouse model of emergency granulopoiesis we observe transcriptional changes in HSCs as early as 4 h after lipopolysaccharide (LPS) administration. We observe that the HSC identity is changed towards a myeloid-biased HSC and show that CD201 is enriched in lymphoid-biased HSCs. While CD201 expression under steady-state conditions reveals a lymphoid bias, under emergency granulopoiesis loss of CD201 marks the lymphoid-to-myeloid transcriptional switch. Mechanistically, we determine that lymphoid-biased CD201+ HSCs act as a first response during emergency granulopoiesis due to direct sensing of LPS by TLR4 and downstream activation of NF-κΒ signaling. The myeloid-biased CD201- HSC population responds indirectly during an acute infection by sensing G-CSF, increasing STAT3 phosphorylation, and upregulating LAP/LAP* C/EBPβ isoforms. In conclusion, HSC subpopulations support early phases of emergency granulopoiesis due to their transcriptional rewiring from a lymphoid-biased to myeloid-biased population and thus establishing alternative paths to supply elevated numbers of granulocytes.


Functional Design of Dielectric-Metal-Dielectric-Based Thin-Film Encapsulation with Heat Transfer and Flexibility for Flexible Displays.
In this study, a new and efficient dielectric-metal-dielectric-based thin-film encapsulation (DMD-TFE) with an inserted Ag thin film is proposed to guarantee the reliability of flexible displays by improving the barrier properties, mechanical flexibility, and heat dissipation, which are considered to be essential requirements for organic light-emitting diode (OLED) encapsulation. The DMD-TFE, which is composed of Al2O3, Ag, and a silica nanoparticle-embedded sol-gel hybrid nanocomposite, shows a water vapor transmission rate of 8.70 × 10-6 g/m2/day and good mechanical reliability at a bending radius of 30 mm, corresponding to 0.41% strain for 1000 bending cycles. The electrical performance of a thin-film encapsulated phosphorescent organic light-emitting diode (PHOLED) was identical to that of a glass-lid encapsulated PHOLED. The operational lifetimes of the thin-film encapsulated and glass-lid encapsulated PHOLEDs are 832 and 754 h, respectively. After 80 days, the thin-film encapsulated PHOLED did not show performance degradation or dark spots on the cell image in a shelf-lifetime test. Finally, the difference in lifetime of the OLED devices in relation to the presence and thickness of a Ag film was analyzed by applying various TFE structures to fluorescent organic light-emitting diodes (FOLEDs) that could generate high amounts of heat. To demonstrate the difference in heat dissipation effect among the TFE structures, the saturated temperatures of the encapsulated FOLEDs were measured from the back side surface of the glass substrate, and were found to be 67.78, 65.12, 60.44, and 39.67 °C after all encapsulated FOLEDs were operated at an initial luminance of 10 000 cd/m2 for sufficient heat generation. Furthermore, the operational lifetime tests of the encapsulated FOLED devices showed results that were consistent with the measurements of real-time temperature profiles taken with an infrared camera. A multifunctional hybrid thin-film encapsulation based on a dielectric-metal-dielectric structure was thus effectively designed considering the transmittance, gas-permeation barrier properties, flexibility, and heat dissipation effect by exploiting the advantages of each separate layer.


Expression of c-erbB-2 in human pancreatic adenocarcinomas.
The c-erbB-2 (neu) gene encodes a transmembrane phosphoglycoprotein (p185erbB-2) which resembles a growth factor receptor-like molecule closely related to the epidermal growth factor receptor. Overexpression of c-erbB-2 induces cell transformation in vitro. Poorer survival rates and elevated recurrence rates following treatment have been shown in patients whose breast adenocarcinomas demonstrate increased c-erbB-2 expression. Using immunoprecipitation and immunoperoxidase staining, we surveyed human cell lines for p185erbB-2. Cell lines from most tumor types (e.g. lymphomas, neuroblastomas, melanomas) demonstrated negligible p185erB-2; however, 3 of 6 pancreatic cell lines overexpressed c-erbB-2. Southern blot analysis revealed that c-erbB-2 was amplified in two of these cell lines and was both rearranged and amplified in one of them. Based on these findings, we examined tissue sections from archival specimens of primary human pancreatic adenocarcinomas. A substantial proportion of specimens had increased p185erbB-2, as judged by increased immunostaining of the tumor cells. In such pancreatic tumors p185erbB-2 may contribute to the malignant phenotype and could provide a target for immunodiagnostic or immunotherapeutic strategies.


Ultrasonographic diagnosis of pancreatic carcinoma supplemented with CT or ERCP.
The practicability of ultrasonography as the primary imaging method for pancreatic carcinoma was studied in a series of 64 patients with pancreatic carcinoma examined and operated on more than 2 years previously, and CT and ERCP were compared for their expedience in the further examination of uncertain sonographic findings. Ultrasound revealed 42 carcinomas definitely and 8 carcinomas uncertainly (78%) and further indicated dilatation of bile and/or pancreatic ducts in 10 patients. Three sonographic examinations failed, and one resulted in a false negative finding (error of interpretation). ERCP proved to be a little more informative than CT in the further examinations.


Protective effects of NAC and salubrinal on apoptosis of retinal pigment epithelial cells induced by all-trans retinoic acid.
Accumulation of endogenous all-trans retinoic acid (ATRA) plays a role in the degeneration of photoreceptor cells and retinal pigment epithelium (RPE) cells, contributing to age-related macular degeneration (AMD). This study attempted to investigate the influence of antioxidant N-acetylcysteine (NAC) and selective endoplasmic reticulum stress (ERS) inhibitor salubrinal on apoptosis of ARPE-19 cells induced by ATRA. The RPE cell line (ARPE-19) was treated with ATRA, ATRA+NAC, ATRA+salubrinal or ATRA+NAC+salubrinal and the control was untreated. After 24 h of cell culture, the levels of apoptosis, multicaspase and reactive oxygen species (ROS) were detected by flow cytometry. Western blot analysis was employed to detect the expression of vascular endothelial growth factor-A (VEGF-A), C/EBP homologous protein (CHOP) and cleaved caspase-3 in the groups. The results of flow cytometry showed that NAC and salubrinal decreased the levels of apoptosis, ROS and multicaspase. ATRA increased VEGF-A levels associated with neovascularisation. NAC and salubrinal inhibited an increase in VEGF-A, CHOP and caspase-3 caused by ATRA in ARPE-19 cells. In ARPE-19 cells, the levels of ROS and ERS can be increased by ATRA, contributing to apoptosis, which can be effectively inhibited by NAC and salubrinal. Thus, ATRA may play an important role in the prevention, diagnosis and treatment of age-related macular degeneration.


Effect of growing forage legumes on the migration and survival in the pasture of gastrointestinal nematodes of sheep.
In order to identify types of forage that inhibit pasture contamination, an evaluation was performed of the effect of the forage legumes Trifolium repens (white clover), Trifolium pratense (red clover) and Lotus corniculatus (bird's-foot-trefoil) on the survival and migration of infective larvae (L3) of gastrointestinal nematodes (GIN) of sheep. An experimental area of 441 m2 was divided into four blocks, subdivided into areas of 1.20 × 1.20 in which the three forage legumes were separately overseeded. After growth of the forage in each subdivision, experimental units were established that were later artificially contaminated with sheep faeces containing GIN eggs. Between October and December 2018, pasture, faecal and soil samples were collected on four occasions during weeks 1, 2, 4 and 8 after the deposition of faeces. In week 6, the forage legumes in all the experimental units were mown to simulate grazing. The number of L3 was quantified to determine their survival in the pasture, faeces and soil. In addition, the horizontal migration of L3 was measured at two distances from the faecal pellets (10 and 30 cm), as well as their vertical migration at two heights of the plant stems, that is, lower half and upper half. Larvae vertical migration was affected by the forage species (P < 0.001), in that bird's-foot-trefoil contained fewer larvae in the upper stratum. Bird's-foot-trefoil restricted the migration of L3 to the upper stratum of the plant, which could potentially decrease the risk of infection by intestinal nematodes in grazing sheep.


Slow crabs - fast genomes: Locomotory capacity predicts skew magnitude in crustacean mitogenomes.
Base composition skews (G-C/G+C) of mitochondrial genomes are believed to be primarily driven by mutational pressure, which is positively correlated with metabolic rate. In marine animals, metabolic rate is also positively correlated with locomotory capacity. Given the central role of mitochondria in energy metabolism, we hypothesised that selection for locomotory capacity should be positively correlated with the strength of purifying selection (dN/dS), and thus be negatively correlated with the skew magnitude. Therefore, these two models assume diametrically opposite associations between the metabolic rate and skew magnitude: positive correlation in the prevailing paradigm, and negative in our working hypothesis. We examined correlations between the skew magnitude, metabolic rate, locomotory capacity, and several other variables previously associated with mitochondrial evolution on 287 crustacean mitogenomes. Weakly locomotory taxa had higher skew magnitude and ω (dN/dS) values, but not the gene order rearrangement rate. Skew and ω magnitudes were correlated. Multilevel regression analyses indicated that three competing variables, body size, gene order rearrangement rate, and effective population size, had negligible impacts on the skew magnitude. In most crustacean lineages selection for locomotory capacity appears to be the primary factor determining the skew magnitude. Contrary to the prevailing paradigm, this implies that adaptive selection outweighs nonadaptive selection (mutation pressure) in crustaceans. However, we found indications that effective population size (nonadaptive factor) may outweigh the impact of locomotory capacity in sessile crustaceans (Thecostraca). In conclusion, skew magnitude is a product of the interplay between adaptive and nonadaptive factors, the balance of which varies among lineages.


Bedtime ethanol increases resistance of upper airways and produces sleep apneas in asymptomatic snorers.
Nasal continuous positive airway pressure (nasal CPAP) and polysomnography were used to analyze the time course of the effect of bedtime ethanol on resistance of upper airways and on the number of respiratory pauses during sleep. On one night, six asymptomatic nonalcoholic male snorers drank 2 ml/kg of 100 proof vodka mixed in orange juice (ethanol dose, 0.79 gm/kg, giving a peak blood alcohol level of 71.8 +/- 33.3 mg/dl). On a second night they received a placebo (1-2 drops of vodka floated on top of the orange juice). We measured (a) the minimum nasal (CPAP) required to eliminate snoring, (b) the number of hypopneas and apneas during each hour of sleep and (c) the arterial oxygen saturation (SaO2) by ear oximetry. On the alcohol night there was a significant increase in the CPAP pressure required to eliminate snoring (placebo 4.8 +/- 1.7 cm H2O, alcohol 6.2 +/- 1.5 cm H2O). The number of respiratory events per hour of sleep (apnea index) was 7.5 +/- 2.1 for ethanol nights versus 3.8 +/- 2.7 for placebo nights (p less than 0.0125). An apnea index of greater than 5 is generally considered abnormal. There was no significant difference in the number of desaturation events (declines of 4% or more in the SaO2) or in the mean SaO2, but the minimum SaO2 was significantly lower on the ethanol night (placebo 89.8% +/- 1.6, alcohol 86.8% +/- 2.7, p less than 0.05). The effect of this dose of alcohol on airway resistance was most pronounced during the first 2 hr after ingestion.


Animal vaccination and the veterinary pharmaceutical industry.
The market for veterinary vaccines is spread across species but it is limited in size and the development of vaccines is becoming more complex and expensive. Vaccines are amongst the most effective means of preventing disease in both animals and humans. In many cases, diseases have been eradicated or their impact on animal health and welfare greatly reduced. It is an ethical responsibility to ensure the availability of a wide range of vaccines even where the market needs to be financially supported, as in the case of less common animal species and those with less common conditions (commonly referred to by the acronym MUMS: Minor Use and Minor Species). Mass slaughter is becoming unacceptable to society and we must move to a 'vaccinate to live' policy wherever possible. We need to use vaccines to avoid the high costs of disease and to enhance food safety. In developing vaccines, we need to minimise animal testing. In addition, we need to ensure that the public acceptthe use of vaccines in food-producing animals as a means of protecting the health and welfare of all animals. As we look to the future, vaccines will be vital to ensure our ability to provide more food to a growing global population. The European Technology Platform for Global Animal Health has a key role to play in identifying key research priorities.


Fate of β-blockers in aquifer material under nitrate reducing conditions: batch experiments.
The fate of the three environmentally relevant β-blockers atenolol, metoprolol and propranolol has been studied in batch experiments involving aquifer material and nitrate reducing conditions. Results from the about 90 d long tests indicate that abiotic processes, most likely sorption, jointly with biotransformation to atenololic acid were responsible for the 65% overall removal observed for atenolol. Zero order kinetics, typical of enzyme-limited reactions, controlled the transformation of this beta blocker to its corresponding carboxylic acid. The mass balance evidences that no mineralization of atenolol occurs in the biotic experiment and that atenololic acid is more stable than its parent compound under the studied conditions. This finding stresses the importance of considering atenololic acid as target compound in the environmental studies on the fate of atenolol. For metoprolol and propranolol the results from the experiment suggest a slower sorption to be the dominant removal process, which led to final decreases in concentrations of 25-30% and 40-45%, respectively. Overall, the removals observed in the experiments suggest that subsurface processes potentially constitute an alternative water treatment for the target beta-blockers, when compared to the removals reported for conventional wastewater treatment plants.


Screening of hepatocellular cancer: Japanese strategy.
In Japan, hepatocellular carcinoma ranks as the fourth most common cancer and is responsible for about 40,000 deaths annually. Accordingly, the development of a screening system for its early detection will be linked to early treatment with a view to increasing survival. Algorithms for surveillance of hepatocellular carcinoma established in Japan will be useful for its early detection.


Classroom postures of 8-12 year old children.
This study examined classroom postures of 8-12 year old school children in Flanders and related the outcomes to self-reported back or neck pain. Postural behaviours using the portable ergonomic observation (PEO) method and self-reported one-week back and neck pain were studied in 105 children from 41 different class groups. Pupils sat statically for 85% of the time, 28% of which the trunk was bent or flexed forward. For 9% of the time, children sat dynamically and for 36% they used a back rest. Children who spent more time sitting with a flexed trunk reported significantly more thoraco-lumbar pain compared to pain-free children and to children with cervical pain (p < 0.05). Children reporting pain stood for a longer period of time than pain-free children (p < 0.05). It is concluded that prolonged static kyphotic sitting without use of a backrest is common in elementary school children in Flanders.


Do resources bolster coping and does coping buffer stress? An organizational study with longitudinal aspect and control for negative affectivity.
Psychiatric workers facing redeployment completed questionnaire measures of stressors, resources (locus of control and perceived social support), coping, well-being, and negative affectivity, at baseline (N = 109) and 1 year later (loss of 7 participants). Regression analyses of the baseline data suggested that as stressors increased, so did avoidance coping, but less so for those high in internality or perceived social support. Problem-focused coping was bolstered by internality and emotion-focused coping by perceived social support. Other regression analyses, with a longitudinal aspect, suggested that stressors had a deleterious effect on well-being. Problem- and emotion-focused coping had beneficial effects, whereas avoidance coping had a (delayed) deleterious effect. These effects of coping were predominantly main and not buffering effects.


Vaginal misoprostol for induction of labour: a more effective agent than prostaglandin F2 alpha gel and prostaglandin E2 pessary.
To compare labour outcome in women who had labour induced with PGF2 alpha gel, PGE2 vaginal pessary or misoprostol administered intravaginally or orally. Unmasked randomised controlled trial. Department of Obstetrics and Gynaecology, University of Zimbabwe, Harare. Women with a singleton foetus in cephalic presentation after 37 weeks gestation admitted for induction of labour who were randomised to prostaglandin F2 alpha gel (n = 76), prostaglandin E2 pessary (n = 75) and misoprostol administered either intra-vaginally (n = 128) or orally (n = 127). Primary outcome was induction to delivery interval. Secondary outcomes included use of oxytocin during labour, mode of delivery, duration of labour, neonatal condition at delivery and maternal complications. Four hundred and six women admitted for induction of labour with a singleton foetus in cephalic presentation after 37 weeks gestation were enrolled. To estimate the risk with induction using other agents the odds ratio and 95% confidence interval was calculated using the group that received prostaglandin F2 alpha gel as referents. The women were comparable for baseline characteristics. Compared to prostaglandin F2 alpha gel, the need for augmentation with oxytocin in labour was significantly reduced in women induced with prostaglandin E2 pessary (OR 0.46; 95%CI 0.23 to 0.93), vaginal misoprostol (OR 0.34; 95%CI 0.18 to 0.63) and oral misoprostol (OR 0.42; 95%CI 0.22 to 0.78). There was no difference in mode of delivery. There was a significantly reduced risk (OR 0.20; 95%CI 0.04 to 0.86) of Caesarean section (CS) for failure to progress in the vaginal misoprostol group. Labour induced with misoprostol and prostaglandin E2 pessary was significantly shorter than in prostaglandin F2 alpha gel. Vaginal misoprostol significantly shortened the induction to delivery interval. There were more admissions to the neonatal unit in the misoprostol groups. Compared to prostaglandin F2 alpha gel, misoprostol and prostaglandin E2 pessary had reduced need for oxytocin and a shorter duration of labour. Effects of misoprostol on the foetus need further investigation before it is used as a routine agent for induction of labour.


Organotypic cultures of cerebellar slices as a model to investigate demyelinating disorders.
Demyelinating disorders, characterized by a chronic or episodic destruction of the myelin sheath, are a leading cause of neurological disability in young adults in western countries. Studying the complex mechanisms involved in axon myelination, demyelination and remyelination requires an experimental model preserving the neuronal networks and neuro-glial interactions. Organotypic cerebellar slice cultures appear to be the best alternative to in vivo experiments and the most commonly used model for investigating etiology or novel therapeutic strategies in multiple sclerosis. Areas covered: This review gives an overview of slice culture techniques and focuses on the use of organotypic cerebellar slice cultures on semi-permeable membranes for studying many aspects of axon myelination and cerebellar functions. Expert opinion: Cerebellar slice cultures are probably the easiest way to faithfully reproduce all stages of axon myelination/demyelination/remyelination in a three-dimensional neuronal network. However, in the cerebellum, neurological disability in multiple sclerosis also results from channelopathies which induce changes in Purkinje cell excitability. Cerebellar cultures offer easy access to electrophysiological approaches which are largely untapped and we believe that these cultures might be of great interest when studying changes in neuronal excitability, axonal conduction or synaptic properties that likely occur during multiple sclerosis.


Dicephalus dipus dibrachius twins: report of an autopsy case.
Dicephalus dipus dibrachius twins are a rare form of conjoined twins. An autopsy of conjoined dicephalus twins is reported. The diagnosis was performed during the pregnancy and the family received a judicial authorization for termination of pregnancy. The preterm newborn progressed to cardiac arrest and died following a court order to terminate the pregnancy. The conceptus presented two arms, two legs, a trunk, two heads, and a single umbilical cord. The two spinal columns presented vertebral fusion in the sacral region. The heart exhibited complex malformations. The external genitalia were female; and cytogenetic analysis confirmed female sex (46, XX). This analysis also corroborated the etiopathogenic hypotheses described for this abnormality, which proposes failures in embryonic formation rather than specific chromosomal alterations. Current identification of cases by ultrasound permits medical management and multidisciplinary action with the family, enabling the legal termination of pregnancy.


Preserved anabolic threshold and capacity as estimated by a novel stable tracer approach suggests no anabolic resistance or increased requirements in weight stable COPD patients.
Assessing the ability to respond anabolic to dietary protein intake during illness provides important insight in the capacity of lean body mass maintenance. We applied a newly developed stable tracer approach to assess in one session in patients with chronic obstructive pulmonary disease (COPD) and healthy older adults both the minimal amount of protein intake to obtain protein anabolism (anabolic threshold) and the efficiency of dietary protein to promote protein anabolism (anabolic capacity). We studied 12 clinically and weight stable patients with moderate to very severe COPD (mean ± SE forced expiratory volume in 1 s: 36 ± 3% of predicted) and 10 healthy age-matched older adults. At 2-h intervals and in consecutive order, all participants consumed a mixture of 0.0, 0.04, 0.10 and 0.30 g hydrolyzed casein protein×kg ffm-1×2 h-1 and carbohydrates (2:1). We assessed whole body protein synthesis (PS), breakdown (PB), net PS (PS-PB) and net protein balance (phenylalanine (PHE) intake - PHE to tyrosine (TYR) hydroxylation) by IV primed and continuous infusion of L-[ring-2H5]PHE and L-[13C9,15N]-TYR. Anabolic threshold (net protein balance = 0) and capacity (slope) were determined on an individual basis from the assumed linear relationship between protein intake and net protein balance. We confirmed a linear relationship between protein intake and net protein balance for all participants (R2 range: 0.9988-1.0, p ≤ 0.0006). On average, the anabolic threshold and anabolic capacity were comparable between the groups (anabolic threshold COPD vs. healthy: 3.82 ± 0.31 vs. 4.20 ± 0.36 μmol PHE × kg ffm-1 × hr-1; anabolic capacity COPD vs. healthy: 0.952 ± 0.007 and 0.954 ± 0.004). At protein intake around the anabolic threshold (0.04 and 0.10 g protein×kg ffm-1×2 h-1), the increase in net PS resulted mainly from PB reduction (p < 0.0001) whereas at a higher protein intake (0.30 g protein×kg ffm-1×2 h-1) PS was also stimulated (p < 0.0001). The preserved anabolic threshold and capacity in clinically and weight stable COPD patients suggests no disease related anabolic resistance and/or increased protein requirements. ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.


[Removal of oral Prevotella intermedia Endotoxin by octyl phenyl polyoxyethylene ether extraction method].
To investigate an effective purification method for removing endotoxin from Prevotella intermedia. The main protein ingredients of bacteria prepared from ammonium sulfate precipitation were further treated with octyl phenyl polyoxyethylene ether (Triton X-114), and then processed at 4°C, 37°C and 25°C. The obtained aqueous phase after at least two more cycle repeated operations was assayed for endotoxin by Western blotting, LAL-clotting method, in vitro cell stimulation and in vivo animal experiments. Western blotting and LAL-clotting method demonstrated that the reduction in endotoxin level was greater than 99.99% and recovery of the proteins after endotoxin removal was greater than 90% with Triton X-114 treatment for 3 cycles. The cytokines expression level was lower in both in vitro cell stimulation and in vivo animal experiments than in untreated group (P < 0.05). The extraction method provides a new choice for endotoxin removal from large volumes of the oral Prevotella intermedia.


In vitro biomechanical analysis of suture methods for flexor tendon repair.
This study was designed to compare five different suture methods that are used clinically for tendon repair. The flexor digitorum profundus tendons from the digits of adult mongrel dogs and adult human cadavers were used as models. The tendons in zone II of the hand, defined as the region from the distal palmar crease to the insertion of the flexor digitorum superficialis tendon at the middle phalanx, were transected and then were repaired by one of the suture methods developed by Kessler, Tsuge, Tajima, Savage, or Lee. The gliding function and tensile properties of the repaired tendons were evaluated biomechanically at time zero. The Tajima and Savage methods produced better gliding function than the other techniques. In the canine specimens that had been repaired by one of these two methods, the rotation of the distal interphalangeal joint was more than 60% of the rotation of the canine control specimens; only the Savage technique produced a rotation 124% that of the human control specimens. After the Tajima repair, the rotation of the proximal interphalangeal joint was 113% that of the canine control specimens and 157% that of the human controls. In the canine specimens that had had the Tajima or Savage repair, excursion of the tendon was greater than 55% that of the controls. The tendons repaired by the Savage method tolerated a significantly higher ultimate load to failure (14 and 25% that of the canine and human control specimens, respectively) than the other methods.(ABSTRACT TRUNCATED AT 250 WORDS)


Action of Caffeine as an Amyloid Inhibitor in the Aggregation of Aβ16-22 Peptides.
Alzheimer's disease (AD) is a neurodegenerative disease caused due to aggregation of Aβ peptides in the brain tissues. Recently, several studies on AD transgenic mice have shown the effect of caffeine in significantly reducing the Aβ amyloid level in their brains. However, the mechanism and mode of caffeine action on amyloid aggregation are not known. Therefore, in this study, we have carried out molecular dynamics simulations of five amyloid-forming Aβ16-22 peptides in pure water and in a regime of caffeine solutions, with different caffeine/peptide stoichiometric ratios. The secondary structure analyses of peptides in pure water show the formation of β-sheet conformations, whereas on addition of caffeine, these ordered conformations become negligible. The radial distribution function, contact map, nonbonding interaction energy, hydrogen bonding, potential of mean force, and hydration analyses show that there is less interpeptide interaction in the presence of caffeine, and the effect is greater with an increasing caffeine ratio. The interaction of aromatic phenylalanine residues of peptides with caffeine restricts the interpeptide interaction tendency. Upon increasing the number of caffeine molecules, interaction of caffeine with other hydrophobic residues also increases. Thus, the hydrophobic core-recognition motif of amyloid formation of peptides is physically blocked by caffeine, thereby abolishing the self-assembly formation.


The dangerousness of mountain recreation: A quantitative overview of fatal and non-fatal accidents in France.
In France, there is a growing enthusiasm for outdoor sports and recreation. In the meantime, the risk of both severe and frequent injury associated with active pursuits in mountain areas is acknowledged. This paper tackles accidents related to mountain sports, with a focus on three critical activities: hiking, mountaineering and ski touring. The aim consists of estimating the actual number of accidents (whether they entailed deaths or injuries) in the three above-mentioned activities. In order to align the information collected, then provide estimations based on the reasoned crossing of these secondary data, we consulted and summarised all the databases available on the French territory. Results address the trauma-related mortality in absolute values, and a comparison with the death rate of other sports. The calculation of a mortality index, including secondary mortality, is then provided. Elements of mountain sports accidentality are also presented, intending to clarify how many casualities occur each year in the French mountains. Last, a focus on the particularities of each mountain sport is provided.