Adherence to Extended Venous Thromboembolism Prophylaxis and Outcomes After Complex Gastrointestinal Oncologic Surgery.
Clinical guidelines recommend extended venous thromboembolism (VTE) prophylaxis for cancer patients after major gastrointestinal (GI) operations. However, adherence to the guidelines has been low, and the clinical outcomes not well defined. This study retrospectively analyzed a random 10 % sample of the 2009-2022 IQVIA LifeLink PharMetrics Plus database, an administrative claims database representative of the commercially insured population of the United States. The study selected cancer patients undergoing major pancreas, liver, gastric, or esophageal surgery. The primary outcomes were 90-day post-discharge VTE and bleeding. The study identified 2296 unique eligible operations. During the index hospitalization, 52 patients (2.2 %) experienced VTE, 74 patients (3.2 %) had postoperative bleeding, and 140 patients (6.1 %) had a hospital stay of at least 28 days. The remaining 2069 operations comprised 833 pancreatectomies, 664 hepatectomies, 295 gastrectomies, and 277 esophagectomies. The median age of the patients was 49 years, and 44 % were female. Extended VTE prophylaxis prescriptions were filled for 176 patients (10.4 % for pancreas, 8.1 % for liver, 5.8 % for gastric cancer, and 6.5 % for esophageal cancer), and the most used agent was enoxaparin (96 % of the patients). After discharge, VTE occurred for 5.2 % and bleeding for 5.2 % of the patients. The findings showed no association of extended VTE prophylaxis with post-discharge VTE (odds ratio [OR], 1.54; 95 % confidence interval [CI], 0.81-2.96) or bleeding (OR, 0.72, 95 % CI, 0.32-1.61). The majority of the cancer patients undergoing complex GI surgery did not receive extended VTE prophylaxis according to the current guidelines, and their VTE rate was not higher than for the patients who received it.


Adolescent exposure to nicotine impairs adult serial pattern learning in rats.
In the present study investigating the effects of adolescent nicotine exposure on adult serial pattern learning, adolescent rats received daily i.p. injections of either 1.0 mg/kg nicotine or saline for 5 days per week for 5 weeks beginning on postnatal day 25 (P25), then were allowed 35 days drug free. Rats then began training on P95 as adults on a 24-element serial pattern composed of eight 3-element chunks. Adolescent exposure to 1.0 mg/kg nicotine produced persistent retardation of learning for the first element of each 3-element chunk of the pattern, that is, for chunk boundary elements, and transient retardation of learning for elements 2 and 3 of each chunk of the pattern, that is, for the within-chunk elements. Deficits at chunk boundaries were interpreted as deficits of phrasing cue discrimination learning whereas deficits for learning responses for elements within-chunks (elements 2 and 3 of chunks) were interpreted as deficits of rule learning. These results indicate that the effects of adolescent nicotine exposure on adult learning and cognitive capacity deserve further scrutiny.


Comparing the effects of MSCs and CD34+ cell therapy in a rat model of myocardial infarction.
Stem cell therapy is considered as a promising approach in the treatment of myocardial infarction (MI). This study was designed as a comparison of human umbilical cord blood (HUCB)-derived CD34+ and HUCB-derived MSCs for the repair of cardiac tissue by induction of the angiogenesis. Forty-eight male rats were randomized into four groups: sham-operated group, MI group, MSCs-treated group, and CD34+ cells-treated group. After 4 weeks, the rats were sacrificed. All sections from left ventricles of all groups were subjected to hematoxylin & eosin, Masson's trichrome, and immunohistochemical stains (CD133, CD44, and α-smooth muscle actin). RNA was extracted for gene expression of the angiogenic markers. A significant reduction of the infarct size and the amplitude of T-wave in the CD34+ cells-treated group when compared with the MSCs-treated group were determined. Histologically, the MI group showed scar tissue, congested blood capillaries around the infarcted area, some necrotic cells, and inflammatory cells. Administration of either MSCs or CD34+ cells had a therapeutic potential to induce regenerative changes in the myocardium with better results in CD34+cells-treated group. Quantitative RT-PCR analysis revealed a significant increase in the expression of vascular endothelial growth factor (VEGF), VEGFR-2, Ang-1, and Tie-2 and a significant decreased expression of Ang-2 in stem cells transplanted groups when compared with the noncell transplanted hearts. A significant increase of VEGF, VEGFR-2, Ang-1, and Tie-2 expression in the group receiving CD34+ cells than those receiving MSCs was found. Finally, there was an upregulation of both human VEGF and human hypoxia-inducible factor 1α in the infarcted hearts treated by CD34+ cells than that treated by MSCs. We first revealed a superior efficacy of CD34+ cells when compared with MSCs in induction of regenerative changes in the MI model. Both cell therapies may repair the damaged heart tissue primarily by secretion of proangiogenic factors that induce the angiogenesis and activate the angiogenesis signaling pathway. © 2016 IUBMB Life, 68(5):343-354, 2016.


Keratosis lichenoides chronica in an Indian child following erythroderma.
A 4-year-old boy presented with mildly itchy, linear, skin lesions over the trunk, arms, and face of 3 months' duration. He had previously been admitted to a private hospital for generalized exfoliation of the skin following drug intake for fever and throat pain. The nature of the drugs was not known. The exfoliative dermatitis was treated with oral prednisolone, 10 mg daily, tapered over 3 weeks. No further topical or oral medication was given. The present skin lesions started 1 month after the cessation of the steroids. There was no family history of skin lesions, voice changes, or systemic complaints. Cutaneous examination showed multiple violaceous, linear, reticulate ridges with adherent scaling over the chest, back, and neck. There were scaly, flat-topped papules over the extensor aspects of both upper arms and the buttocks, and scaly plaques over the cheeks (Figs 1a-d and 2a,b). The scalp showed diffuse greasy scaling. There were no oral, genital, axillary, or eye lesions. The nails were normal. Systemic examination did not reveal any abnormal finding. Routine hematologic investigations, liver and kidney function tests, tests for hepatitis B and C, and enzyme-linked immunosorbent assay (ELISA) for HIV were normal. Histopathology from skin lesions on the back revealed hyperkeratosis, patchy parakeratosis, follicular plugging, alternating irregular acanthosis and epidermal thinning, basal cell degeneration, and a band-like inflammatory infiltrate of lymphocytes, histiocytes, and a few plasma cells (Fig. 3). Based on the classical clinical features and histopathology, keratosis lichenoides chronica was diagnosed, and topical 1% hydrocortisone acetate cream, twice daily, was prescribed. There was slight relief of pruritus at a follow-up visit after 3 weeks; however, the patient was subsequently lost to follow-up.


Hypogammaglobulinaemia.
This article reviews the primary immunodeficiencies that result in hypogammaglobulinemia or predominantly antibody deficiency disorders. This group makes up the largest proportion of patients with primary immunodeficiency. Significant advances have been made in understanding the molecular basis and clinical characteristics of patients with the more severe forms of antibody deficiency in the last 6 years. Recognition of these disorders remains poor with significant diagnostic delay. The milder forms of antibody deficiency disorders, especially those with normal total serum immunoglobulin G levels, remain poorly characterized and understood. Further work remains to be done in understanding and recognizing these syndromes to benefit patient care and foster further knowledge of the immune system.


Gastric bypass leads to improvement of diabetic neuropathy independent of glucose normalization--results of a prospective cohort study (DiaSurg 1 study).
Surprisingly, 40% to 95% of patients with type 2 diabetes mellitus (T2DM) show early remission of hyperglycemia after obesity surgery. It is unknown to what extent other diabetes-associated comorbidities such as distal peripheral neuropathy (DPN) might be influenced by obesity surgery. This pilot study aimed at providing further evidence for the impact of Roux-en-Y gastric bypass (RYGB) on both glycemic control and DPN in non-severely obese patients with insulin-dependent T2DM. In the present prospective cohort study, 20 patients with long-standing, insulin-dependent T2DM and a body mass index (BMI) between 25 and 35 kg/m underwent laparoscopic RYGB. Body mass index, glycosylated hemoglobin (HbA1c), and DPN [quantified by the Neuropathy Symptom Score (NSS) and the Neuropathy Deficit Score (NDS)] were investigated. Six months after surgery, the preoperative BMI of 32.8 ± 2.1 kg/m (mean ± standard deviation) dropped to 25.6 ± 2.5 kg/m (P < 0.001). Preoperative HbA1c levels decreased from 8.5 ± 1.2% to 7.1 ± 1.2% (P < 0.001), with 15% of patients having a normalized HbA1c level lower than 6.2%. Of 12 patients with documented DPN, the median NSS was 8 (range, 0-10) preoperatively and 0 (range, 0-9) postoperatively (P = 0.004), with 8 patients scoring an NSS of 0. The median NDS was 6 (range, 2-8) preoperatively and 4 (range, 0-8) postoperatively (P = 0.027), with 1 patient scoring an NDS of 0. All patients had an improvement or normalization in either 1 or both scores. As expected, BMI and HbA1c levels improved significantly after RYGB. More interestingly, neuropathy scores, such as NSS and NDS, improved significantly early after surgery. Symptomatic neuropathy was completely reversible in 67% of the patients. These findings add further evidence to the fact that RYGB might be a valuable treatment option not only for improving glycemic control but also for reducing diabetes-associated comorbidities, such as DPN. This points to a complex metabolic effect of RYGB that exceeds glucose normalization. However, the results still need to be confirmed in controlled trials.


High dose rate brachytherapy in the treatment of prostate cancer.
The optimal treatment of patients with localized prostate cancer remains controversial. Significant clinical data are available, however, demonstrating that patients treated with radiation therapy (RT) have a significantly better outcome as the dose to the gland is increased. What remains debatable, however, is how to best deliver these higher doses of RT without significantly increasing normal tissue toxicities. Conformal high dose rate brachytherapy (C-HDR BT) represents an alternative means of precise dose delivery that offers similar tumoricidal effects as three-dimensional (3D) conformal external beam radiotherapy (EBRT) or permanent interstitial prostate seed implants with potential additional advantages. Since C-HDR BT consists of temporarily placing afterloading needles or catheters directly into the prostate gland under real-time ultrasound guidance, a steep dose gradient between the prostate and adjacent normal tissues can be generated that is minimally affected by organ motion and edema or treatment setup uncertainties. The ability to control the amount of time the single HDR radioactive source "dwells" at each position along the length of each brachytherapy catheter further enhances the conformity of the dose. In addition, recent radiobiological data on prostate cancer treatment suggest that C-HDR BT should produce tumor control and late normal tissue side effects that are at least as good as achieved with conventional fractionation, with the additional possibility that acute side effects might be reduced. Published data from several groups performing C-HDR BT as boosts in patients with locally advanced disease have supported these assumptions. Combined with the physical advantages discussed above, C-HDR BT should provide similar tumor control as 3D conformal EBRT with the added advantages of reduced treatment times, less acute toxicity, and no additional technological requirements to account and correct for treatment setup uncertainties and organ motion. Due to the success of C-HDR BT as boost treatment in locally advanced disease, this form of radiation treatment has recently been applied to low-risk prostate cancer patients as an alternative brachytherapy technique to permanent interstitial seed implantation. Advantages in this setting include an improved ability to define and deliver the prescribed dose, a significantly shortened treatment schedule compared to 3D conformal EBRT, and the fact that patients are not radioactive after implantation.


Differential regulation of fatty acid biosynthesis in two Chlorella species in response to nitrate treatments and the potential of binary blending microalgae oils for biodiesel application.
This study was undertaken to investigate the effects of different nitrate concentrations in culture medium on oil content and fatty acid composition of Chlorella vulgaris (UMT-M1) and Chlorella sorokiniana (KS-MB2). Results showed that both species produced significant higher (p<0.05) oil content at nitrate ranging from 0.18 to 0.66 mM with C. vulgaris produced 10.20-11.34% dw, while C. sorokiniana produced 15.44-17.32% dw. The major fatty acids detected include C16:0, C18:0, C18:1, C18:2 and C18:3. It is interesting to note that both species displayed differentially regulated fatty acid accumulation patterns in response to nitrate treatments at early stationary growth phase. Their potential use for biodiesel application could be enhanced by exploring the concept of binary blending of the two microalgae oils using developed mathematical equations to calculate the oil mass blending ratio and simultaneously estimated the weight percentage (wt.%) of desirable fatty acid compositions.


Targeting hypoxia in head and neck cancer.
The idea of 'targeting' hypoxia stems from recognition of the fact that oxygen (or its lack) is central to the practice of radiation oncology. Targeting embraces the alternative goals of trying to overcome hypoxia on the one hand and trying to exploit it on the other. This presentation briefly reviews these two approaches with major emphasis on the latter.


Variants in proinflammatory genes IL1RL1, IL1B and IRF4 are associated with overweight in a pediatric Brazilian population.
Obesity is a chronic complex disease with great prevalence for children all over the world. Characterized for low-grade inflammation associated with several comorbidities such as resistance and type 2 diabetes mellitus (T2DM). To investigate whether genetic variants in IL10, IL1RL1, IL1B, IRF4, TNF, IL6, and IL33 genes are associated with being overweight in children. We performed the genotyping of 1004 children using Illumina 2.5 Human Omni bead chip, and association analysis on the genetic variants and the overweight through logistic regression adjusted for sex, age and components principal. Of the seven genes analyzed, 16 SNVs significantly associated. Eleven variants in IL1RL1, two in IL1B and one in IRF4 genes increased overweight risk and two SNVs in IL1RL1 were associated with protection against overweight. The rs2287047-A was negatively associated (OR: 0.66, CI95%: 0.19-0.45) and had a reduced IL1RL1 expression in whole blood (p 0.033) in silico eQTL. The rs12203592-T, in IRF4, was positively associated with being overweight, and led to an increased gene expression in whole blood (p < 0.001) and adipose tissue (p < 0.001). These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children.


Mitigate Cascading Failures on Networks using a Memetic Algorithm.
Research concerning cascading failures in complex networks has become a hot topic. However, most of the existing studies have focused on modelling the cascading phenomenon on networks and analysing network robustness from a theoretical point of view, which considers only the damage incurred by the failure of one or several nodes. However, such a theoretical approach may not be useful in practical situation. Thus, we first design a much more practical measure to evaluate the robustness of networks against cascading failures, termed Rcf. Then, adopting Rcf as the objective function, we propose a new memetic algorithm (MA) named MA-Rcf to enhance network the robustness against cascading failures. Moreover, we design a new local search operator that considers the characteristics of cascading failures and operates by connecting nodes with a high probability of having similar loads. In experiments, both synthetic scale-free networks and real-world networks are used to test the efficiency and effectiveness of the MA-Rcf. We systematically investigate the effects of parameters on the performance of the MA-Rcf and validate the performance of the newly designed local search operator. The results show that the local search operator is effective, that MA-Rcf can enhance network robustness against cascading failures efficiently, and that it outperforms existing algorithms.


Gp80 (clusterin; TRPM-2) mRNA level is enhanced in human renal clear cell carcinomas.
The gp80 glycoprotein complex (clusterin, apolipoprotein J, TRPM-2) is a widely expressed protein that has been attributed functions in tissue remodelling, immune defense and transport of lipids and biologically active peptides. The expression of the protein appears to be elevated in several neurodegenerative, apoptotic and malignant processes. We show here that in patients with renal clear cell carcinoma gp80 mRNA is 3-fold overexpressed in tissue of the tumors compared with adjacent non-tumor tissue.


[An improvement in the terminology of atopic dermatitis-diffuse neurodermatitis].
The problem of dermatologic terminology at large is discussed as exemplified by the synonymous terms concerned with diffuse neurodermatitis.


[Analysis of spontaneous reperfusion in acute myocardial infarction and its effect on short-term prognosis].
To analyse the clinical and angiographic characteristics of spontaneous reperfusion (SR) in AMI, and to evaluate its effect on short-term prognosis. 112 consecutive AMI patients without intravenous thrombolytic therapy received emergent coronary angiography and primary PCI. The patients were divided into SR group (antegrade TIMI grade 2-3 flow) and non-SR group (antegrade TIMI grade 0-1 flow). The clinical, angiographic and prognostic features of the patients were analyzed. 31 patients (27.7%) were in SR group, and there was no significant difference in base-line clinical characteristics between the two groups. Compared with non-SR group, peak values of CK and CK-MB, Ventricular wall motion abnormality and mortality were lower in SR group, ejection fraction was higher in SR group. Logistic regression analysis showed that there was good correlation between SR and peak value of CK, collaterals, ventricular wall motion abnormality and pre-dilation in PCI. SR decreased infarction size, improved heart function and reduced 30-day mortality.


Fungal contamination of Hanks solution.
Laboratory contamination of clinical specimens submitted for cytological examination is an on-going threat that requires continuous vigilance and quality control. We recently were confronted with a suspected fungal infection in a bone aspirate that was found to derive from contaminated Hanks solution used in cytological preparation. Diff-Quik staining of air-dried cytocentrifuged preparations of Hanks fluid as well as any other suspect laboratory fluid is recommended as a routine quality control procedure.


Rates of H2O2 generation from peroxisomal beta-oxidation are sufficient to account for fatty acid-stimulated ethanol metabolism in perfused rat liver.
Fatty acids generate H2O2 via peroxisomal beta-oxidation and increase ethanol metabolism markedly in a system that involves catalase-H2O2. The present studies were conducted to understand why fatty acid-stimulated ethanol metabolism occurs much faster than rates of H2O2 generation reported previously in perfused rat liver. A new method was developed to measure rates of H2O2 generation based on the fact that methanol is oxidized only by catalase in rat liver. Rates of H2O2 generation were estimated from the time necessary for the steady-state level of catalase-H2O2 measured spectrophotometrically (660-640 nm) through a lobe of the liver to return to basal values following the addition of a known quantity of methanol in a closed perfusion system containing 4% bovine serum albumin. Under these conditions, basal rates of H2O2 production and rates of 4-methylpyrazole-insensitive ethanol oxidation were in a similar range (10 to 20 mumol/g/hr). Rates of H2O2 generation were increased up to 80 mumol/g/hr by addition of laurate, palmitate or oleate (1 mM); half-maximal increases in rates were observed with 0.6 mM oleate. Hexanoate, a short-chain fatty acid, did not stimulate H2O2 production or ethanol uptake. In these studies, rates of H2O2 generation compared well with rates of fatty acid-stimulated ethanol uptake measured in the presence of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, with all fatty acids studied. It is concluded, therefore, that rates of H2O2 generation are sufficient to account for rates of fatty acid-stimulated ethanol metabolism via catalase-H2O2. In addition, these data indicate that catalase may contribute significantly to ethanol oxidation under physiological conditions in the presence of fatty acids.


Safety assessment of the methanol extract of the stem bark of Amphimas pterocarpoides Harms: Acute and subchronic oral toxicity studies in Wistar rats.
Amphimas pterocarpoides Harms (Leguminosae) is widely used traditionally in Central and West Africa for the treatment of various ailments. However, no data regarding its safety have been published until now. Thus, the present study aimed to investigate the potential toxicity of the methanol extract of the stem bark of Amphimas pterocarpoides (AP) in Wistar rats following the OECD guidelines. In acute oral toxicity, female rats received a single dose of 2000 mg/kg of AP and were observed for 14 days. In subchronic toxicity, doses of 150, 300, 600 mg/kg/day of AP were given per os to rats (males and females) for 28 days. No death and abnormal behaviors were observed in acute toxicity and the LD50 was estimated higher than 5000 mg/kg. In the subchronic study, AP induced no significant variation in body weight and relative weight of organs, whereas a delayed decrease of white blood cell count and granulocytes was observed. Inconsistent increase of the total cholesterol/high density lipoprotein was observed at 600 mg/kg in males. Such variation (not dose dependent) and without biological relevance indicate a wide margin of safety for the traditional use of AP.


Anti-immunoglobulin antibodies. III. Properties of sequential anti-idiotypic antibodies to heterologous anti-gamma globulins. Detection of reactivity of anti-idiotype antibodies with epitopes of Fc fragments (homobodies) and with epitopes and idiotopes (epibodies).
Murine anti-V region antibodies against a human monoclonal protein Gl with anti-gamma-globulin activity and bearing the Wa cross-reactive idiotype were prepared in several strains of mice. Antibodies were obtained that were specific for the Gl idiotype, the Wa cross-reactive idiotype, and for various framework antigenic determinants that were distinguished by a variety of procedures. Synthesis of such antibodies were found to be independent of MHC and Igh gene complexes. These anti-V region antibodies, produced by a majority of mouse strains investigated, also share a cross-reactive idiotype recognized by BALB/c anti-anti-V region Gl antibodies. A fraction of BALB/c anti-anti-V region Gl antibodies displayed human Fc gamma binding activity and, therefore, can be considered homobodies, as described in other systems. Two of the anti-idiotype antibodies obtained in this system exhibited a peculiar property: they interacted not only with their own antigen (IgM Gl), but also with the Fc fragment with which IgM Gl reacts. Thus, A/J anti-V region Gl antibodies bind to the human Fc gamma fragment in addition to IgM Gl. Similarly, a monoclonal CB6 F1 anti-anti-V region Gl antibody interacted with the V region of IgM Gl as well as with the syngeneic anti-V region antibodies. We called these anti-idiotypic antibodies epibodies because they interact with epitopes of the primary antigen. These homobodies and epibodies, obtained by immunization across heterologous barriers, represent new examples of recognition of the internal image of the antigen within the immune system.


State of Stress-Marker Organs in Rats with Various Behavioral Characteristics during Repeated Stress Exposures.
Changes in the relative weight of stress-marker organs in rats with various behavioral patterns in the open-field test were studied after repeated stress exposures on the model of daily 4-h immobilization over 8 days. Involution of the thymus and spleen in behaviorally passive specimens was found after single stress, as well as under conditions of 3- and 8-fold immobilizations. The weight of these organs in active animals remained practically unchanged after acute stress, but decreased on day 3 and particularly on day 8 of repeated stress exposures. As differentiated from passive rats (open-field test), behaviorally active specimens were characterized by hypertrophy of the adrenal glands after single and 3-fold stress procedures. Our results complement the data on individual features of the peripheral and central mechanisms for the stress response in mammals. These data illustrate the importance of individual approach to studying systemic organization of physiological functions under normal conditions and during negative emotiogenic exposures.


[Constant Duméril (1774-1860) anatomist doctor and naturalist, about a portrait by G. Devers].
André, Marie, Constant Duméril (1774-1860) served as a professor in the << faculté de médecine de Paris >> from 1801 to 1855. He was also chairman of herpetology and ichthyology of the << Muséum national d'histoire naturelle >> in Paris. The Paris-Descartes University (department of anatomy) owns a great, framed portrait which is an oil painting by Giuseppe Devers, 1855, representing C. Duméril sat on a chair. The study of his portrait, biography and bibliography brings precisions on a noticeable scholar of the anatomical and naturalistic field in Paris in the first half of the 19th century.


Preliminary characterization of a thermostable DNA polymerase I from a mesophilic Bacillus sphaericus strain C3-41.
A thermostable DNA polymerase I from a mesophilic Bacillus sphaericus strain C3-41 was characterized in this study. The polI was cloned, sequenced and over-expressed in Escherichia coli. The expressed 110 kDa fusion protein of PolI was stable at 70 degrees C for 1 h. Compared with DNA polymerase I of E. coli (TaKaRa), the relative polymerase activity of this PolI was 3.33 +/- 0.1 RFU microl(-1) at 37 degrees C using fluorescent quantitative analysis. It showed higher polymerase activity than E. coli PolI at higher temperature, with a relative activity of 3.75 +/- 0.1 RFU microl(-1) at 70 degrees C. The polI sequence analysis and the protein structure prediction indicated that this protein had a high similarly to other PolI from thermophilic micro-organisms. This information is of importance for future study for evolution of the house-keeping gene polI in entomopathogenic bacterium B. sphaericus.


The gamma-Na+,K+-ATPase subunit assembles selectively with alpha1/beta1-Na+,K+-ATPase but not with the colonic H+,K+-ATPase.
The ubiquitous Na+-pump (Na+,K+-ATPase) assembles as a heterodimer of composition alpha/beta in some nephron segments, while in other segments it may exist as a heterotrimer of composition alpha/beta/gamma. The gamma-subunit has been reported to increase the affinity of the Na+-pump for adenosine 5'-triphosphate (ATP), and decrease affinity for both Na+ and K+. The alpha-subunit of the colonic H+,K+-ATPase (cHK) shares 75% sequence similarity with alpha1-Na+,K+-ATPase (alpha1) and assembles with beta1-Na+,K+-ATPase (beta1) in distal colon and renal medulla. Differences in pharmacological properties have been ascribed to when heterologously expressed function has been compared to function in vitro. The purpose of this study was to determine if cHK might associate with the gamma-subunit of the Na+,K+-ATPase (gamma) as a possible explanation for these variations in function. An antibody specific for the gamma was used in coimmunoprecipitation experiments to determine if the gamma assembles stably in vitro with cHK and beta1 in rat renal medulla or distal colon. Our results demonstrate that the gamma-subunit assembles specifically with the Na+-pump, but not with cHK. Furthermore, the gamma-subunit assembly was specific for rat kidney and was not observed in distal colon. Since the gamma-subunit did not assemble with the cHK/beta1 complex, gamma-subunit assembly cannot explain those variations in ex vivo and in vitro pharmacologic properties ascribed to cHK.


A modified oddball paradigm for investigation of neural correlates of attention: a simultaneous ERP-fMRI study.
The objective of the presented study was to develop and evaluate a P300 experimental protocol for simultaneous registration of event-related potentials (ERPs) and functional MRI (fMRI) data with continuous imaging. It may be useful for investigating attention and working memory processes in specific populations, such as children and neuropsychiatric patients. Eleven children were investigated with simultaneous ERP-fMRI. To fulfill requirements of both BOLD and electroencephalographic signal registration, a modified oddball task was used. To verify the ERP-fMRI protocol we also performed a study outside the scanner using a typical two-stimuli oddball paradigm. Localization of the P300 component of ERPs partially corresponded with fMRI results in the frontal and parietal brain regions. FMRI activations were found in: middle frontal gyrus, insula, SMA, parietal lobule, thalamus, and cerebellum. Our modified oddball task provided ERP-fMRI results with high level of significance (EEG SNR=35, fMRI p<0.05-Bonf.). ERPs obtained in the scanner were comparable with those registered outside the scanner, although some differences in the amplitude were noticed, mainly in the N100 component. In our opinion the presented paradigm may be successfully applied for simultaneous ERP-fMRI registration of neural correlates of attention in vulnerable populations.


Revealing cryptic spatial patterns in genetic variability by a new multivariate method.
Increasing attention is being devoted to taking landscape information into account in genetic studies. Among landscape variables, space is often considered as one of the most important. To reveal spatial patterns, a statistical method should be spatially explicit, that is, it should directly take spatial information into account as a component of the adjusted model or of the optimized criterion. In this paper we propose a new spatially explicit multivariate method, spatial principal component analysis (sPCA), to investigate the spatial pattern of genetic variability using allelic frequency data of individuals or populations. This analysis does not require data to meet Hardy-Weinberg expectations or linkage equilibrium to exist between loci. The sPCA yields scores summarizing both the genetic variability and the spatial structure among individuals (or populations). Global structures (patches, clines and intermediates) are disentangled from local ones (strong genetic differences between neighbors) and from random noise. Two statistical tests are proposed to detect the existence of both types of patterns. As an illustration, the results of principal component analysis (PCA) and sPCA are compared using simulated datasets and real georeferenced microsatellite data of Scandinavian brown bear individuals (Ursus arctos). sPCA performed better than PCA to reveal spatial genetic patterns. The proposed methodology is implemented in the adegenet package of the free software R.


Early treatment of ureteral injuries found after gynecological surgery.
Five consecutive patients with 7 ureteral injuries found after gynecological operations were treated conservatively. The complications ensuing this type of management are reported briefly. Twenty more consecutive patients with 27 ureteral injuries were treated immediately after diagnosis and definitively. Important points of technique are 1) little attempt to stay extraperitoneally, 2) sacrifice of all abnormal ureter, 3) re-establishment of ureteral continuity between a normal ureter and the bladder by usual means, 4) peritoneal closure only when easy, 5) adequate drainage and 6) use of antibiotics. The results obtained were excellent. Early and definitive treatment of ureteral injuries found after gynecological operations seems to be the safest and easiest type of management in all cases.


Behavioral mapping of children's physical activities and social behaviors in an indoor preschool facility: methodological challenges in revealing the influence of space in play.
GIS (Geographic Information Systems) based behavior maps are useful for visualizing and analyzing how children utilize their play spaces. However, a GIS needs accurate locational information to ensure that observations are correctly represented on the layout maps of play spaces. The most commonly used tools for observing and coding free play among children in indoor play spaces require that locational data be collected alongside other play variables. There is a need for a practical, cost-effective approach for extending most tools for analyzing free play by adding geospatial locational information to children's behavior data collected in indoor play environments. We provide a non-intrusive approach to adding locational information to behavior data acquired from video recordings of preschool children in their indoor play spaces. The gridding technique showed to be a cost-effective method of gathering locational information about children from video recordings of their indoor physical activities and social behaviors. Visualizing the proportions of categories and observed intervals was done using bubble pie charts which allowed for the merging of multiple categorical information on one map. The addition of locational information to other play activity and social behavior data presented the opportunity to assess what types of equipment or play areas may encourage different physical activities and social behaviors among preschool children. Gridding is an effective method for providing locational data when analyzing physical activities and social behaviors of preschool children in indoor spaces. It is also reproducible for most GIS behavior mapping focusing on indoor environments. This bypasses the need to have positioning devices attached to children during observations, which can raise ethical considerations regarding children's privacy and methodological implications with children playing less naturally. It also supports visualizations on behavior maps making them easier to interpret.


Increased phosphorylation of AKAP by inhibition of phosphatidylinositol 3-kinase enhances human sperm motility through tail recruitment of protein kinase A.
Sperm motility is regulated by a complex balance between kinases and phosphatases. Among them, phosphatidylinositol 3-kinase (PI 3-kinase) has been recently suggested to negatively regulate sperm motility (Luconi, M., Marra, F., Gandini, L., Lenzi, A., Filimberti, E., Forti, G. and Baldi, E. (2001). Hum. Reprod. 16, 1931-1937). We demonstrate the presence and activity of PI 3-kinase in human spermatozoa and have investigated the molecular mechanism(s) by which the PI 3-kinase inhibitor, LY294002, triggers an increase in sperm motility. PI 3-kinase inhibition results in an increase in intracellular cAMP levels and in tyrosine phosphorylation of the protein kinase A-anchoring protein AKAP3. These effects finally result in a stimulation of protein kinase A (PKA) binding to AKAP3 in sperm tails through the regulatory subunit RIIbeta. The increased binding of RIIbeta to AKAP3 induced by LY294002 is mainly due to tyrosine phosphorylation of AKAP3, since it is completely blocked by the tyrosine kinase inhibitor erbstatin, which also reverses the effects of LY294002 on motility and suppresses PKA-AKAP3 interaction. The requirement of PKA binding to AKAP3 for sperm motility is confirmed by the reduction of motility induced by an inhibitor of RIIbeta-AKAP3 binding, Ht31, whose effects on sperm motility and PKA binding to AKAP3 are reversed by LY294002. These results demonstrate that PI 3-kinase negatively regulates sperm motility by interfering with AKAP3-PKA binding, providing the first evidence of a molecular mechanism by which PKA can be targeted to sperm tails by interaction with tyrosine phosphorylated form of AKAP3.


Clostridium difficile outbreak caused by NAP1/BI/027 strain and non-027 strains in a Mexican hospital.
Clostridium difficile infections caused by the NAP1/B1/027 strain are more severe, difficult to treat, and frequently associated with relapses. A case-control study was designed to examine a C. difficile infection (CDI) outbreak over a 12-month period in a Mexican hospital. The diagnosis of toxigenic CDI was confirmed by real-time polymerase chain reaction, PCR (Cepheid Xpert C. difficile/Epi). During the study period, 288 adult patients were evaluated and 79 (27.4%) patients had confirmed CDI (PCR positive). C. difficile strain NAP1/B1/027 was identified in 31 (39%) of the patients with confirmed CDI (240 controls were included). Significant risk factors for CDI included any underlying disease (p<0.001), prior hospitalization (p<0.001), and antibiotic (p<0.050) or steroid (p<0.001) use. Laboratory abnormalities included leukocytosis (p<0.001) and low serum albumin levels (p<0.002). Attributable mortality was 5%. Relapses occurred in 10% of patients. Risk factors for C. difficile NAP1/B1/027 strain infections included prior use of quinolones (p<0.03). Risk factors for CDI caused by non-027 strains included chronic cardiac disease (p<0.05), chronic renal disease (p<0.009), and elevated serum creatinine levels (p<0.003). Deaths and relapses were most frequent in the 027 group (10% and 19%, respectively). C. difficile NAP1/BI/027 strain and non-027 strains are established pathogens in our hospital. Accordingly, surveillance of C. difficile infections is now part of our nosocomial prevention program.


Two different centered monoclinic crystals of the E. coli outer-membrane protein OmpF originate from the same building block.
Macromolecule crystal formation can be divided in two major steps: 1. the formation of a nucleus and 2. the growth of this nucleus into a full mature crystal. The latter is well described and understood, while the former remains elusive due to the difficulty to study it and is described by nucleation theories. Here we report the structure of the Escherichia coli outer membrane porin OmpF in two centered monoclinic space groups. Strikingly, the two crystals originate from the same building block, made of two trimers of OmpF interacting via their rough side. The different crystallization conditions trigger the formation of distinct arrangement of these building blocks, leading to the formation of translational non-crystallographic symmetry (tNCS) in one case, made possible by the loose lateral packing mediated by detergents. In light of nucleation theories, these results allow us to speculate that these two crystals originate from nuclei made of either clusters of building blocks, or already forming columns that later associate laterally using detergents as glue.


[Migraine and patent foramen ovale].
Observational studies indicate an increased prevalence of patent foramen ovale (PFO) in migraineurs with aura and an increased prevalence of migraine and migraine with aura in patients with PFO but a recent stratified meta-analysis does not support pairwise association between PFO and migraine. There are conflicting data regarding causal relationship between these two conditions. According to recent studies, microembolization might provoke a decrease in cerebral oxygen saturation, thus triggering cortical spreading depression and, thereafter, migraine with aura attack. Release of vasoactive substances by activated platelets or atrial natriuretic factor are other pathophysiological explanations. Retrospective analyses of PFO closure suggest clinically significant improvements in migraine patterns. The MIST study is the only prospective study available with a good design but this study gave a negative response about cure of migraine with aura and revealed a high morbidity for such a benign condition. Although PFO closure sometimes appears to affect migraine patterns favorably, the very low grade of available evidence to support this association precludes definitive conclusions. To date, PFO closure in migraineurs with aura is not recommended in daily practice.


Default Network and Aging: Beyond the Task-Negative Perspective.
During cognitive tasks requiring externally directed attention, activation in the default-network (DN) typically decreases below baseline levels ('deactivation'). Healthy aging is associated with reduced deactivation, which is usually attributed to a failure to suppress DN processes. Recent evidence instead suggests that older adults may be more reliant on DN than young adults when performing these tasks.


Circular RNA hsa_circ_0011298 enhances Taxol resistance of non-small cell lung cancer by regulating miR-486-3p/CRABP2 axis.
Circular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non-small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC. Circ_0011298, microRNA-486-3p (miR-486-3p), and CRABP2 mRNA expression were determined using qRT-PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual-luciferase reporter and RIP assays were performed to confirm the relationship between miR-486-3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo. Circ_0011298 was overexpressed in Taxol-resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol-resistant NSCLC cells. Circ_0011298 was a sponge of miR-486-3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR-486-3p inhibition. Moreover, miR-486-3p directly targeted CRABP2, and miR-486-3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR-486-3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo. Circ_0011298 elevated Taxol resistance of NSCLC by sponging miR-486-3p and upregulating CRABP2, providing a possible circRNA-targeted therapy for NSCLC.


[A recording method for locomotor activity of small insects].
The method described in this paper enables the locomotor activity of small insects to be recorded. It is based on variations in capacitance within a bridge circuit, the variations being due to movements of the animals. The method is adapted to the use of multi-channel action recorders, thus allowing a greater number of sensor units to be employed simultaneously.As an example of application, a comparison is made between the diurnal rhythmicity patterns of locomotor activity inDrosophila melanogaster andDrosophila azteca. Both species show maximal activity in the morning and in the evening.D. melanogaster is active throughout the middle of the day as well, butD. azteca, being adapted to an arid climate, shows a resting period during this time of day.


Tumor necrosis factor α induces myofibroblast differentiation in human tongue cancer and promotes invasiveness and angiogenesis via secretion of stromal cell-derived factor-1.
Cancer-associated fibroblasts (CAFs) play an important role in tumor progression and are associated with a poor prognosis. Tumor necrosis factor α (TNFα) has been involved in growth and metastasis associated with epithelial-mesenchymal transition (EMT) in many types of cancers. However, the relationship among the TNFα, activation of CAFs and their tumor-promoting effects on tongue squamous cell carcinoma (TSCC) remain obscure. A series of matched primary CAFs and normal fibroblasts (NFs) pairs were cultured, and additionally two TSCC cell lines SCC9 and CAL27, were treated with TNFα or CAFs derived stromal cell-derived factor-1 (SDF1) respectively to study invasion and EMT in vitro. In addition, NFs were treated with TNFα to detect the expression of myofibroblast markers, invasion, induced collagen gel contraction and enhanced cancer metastasis. Finally, invasion and angiogenesis of human vein endothelial cells (HUVECs) treated with TNFα and CAFs derived SDF1 was measured. TNFα and CAFs-derived SDF1 induced TSCC cells metastasis and EMT separately. TNFα facilitated the transformation of NFs to CAFs-like fibroblasts, which was accompanied by acquisition of similar myofibroblast markers expression and malignant function to CAFs. Furthermore, TNFα and CAFs derived SDF1 also promoted invasion and angiogenesis of HUVECs. These results suggest that TNFα may not only directly but also indirectly enhance cancer metastasis, EMT and angiogenesis formation in tongue cancer through myofibroblast differentiation via SDF1 secretion.


Obesity Is Associated With Increased Thoracic Kyphosis in Adolescent Idiopathic Scoliosis Patients and Nonscoliotic Adolescents.
Retrospective comparative cohort study. To compare radiographic parameters between adolescents with a greater body mass index (BMI) percentile to underweight individuals. Increased BMI percentile has been associated with increased complications after surgical correction of adolescent idiopathic scoliosis (AIS). However, association between BMI percentile and preoperative sagittal plane alignment has not been evaluated. The purpose of this study was to evaluate the effect of BMI percentile on sagittal alignment in AIS patients compared with nonscoliotic adolescents. Posterior-anterior and lateral spinal radiographs of 1,551 AIS patients with a thoracic major curve (Lenke 1-4) and 70 nonscoliotic adolescent patients were compared. BMI percentile was determined based on age and sex, and patients were divided into four categories: underweight (<5th percentile), normal-weight (5th-85th percentile), overweight (85th-95th percentile), and obese (≥95th percentile). Coronal plane deformity magnitude was not significantly different between the 4 categories of AIS patients (p = .51). Increased BMI percentile was associated with increased thoracic kyphosis globally (T2-T12: p < .005) as well as segmentally (T2-T5: p < .001; T5-T12: p < .001) in patients with AIS. This was also true in obese adolescents without spinal deformity (p < .04). Lumbar lordosis, pelvic incidence, and pelvic tilt were not significantly different between AIS patients in the four BMI percentile categories (p > .07). Pelvic incidence was significantly greater in AIS patients compared with nonscoliotic adolescents (54 ± 13 vs. 46 ± 11; p = .01). Increased BMI percentile is associated with increased thoracic kyphosis in AIS patients and nonscoliotic adolescents. Excess weight may reduce anterior vertebral growth. AIS patients have an increased pelvic incidence compared with nonscoliotic adolescents; however, this variable is not influenced by body mass. These relationships should be taken into account when planning sagittal plane deformity correction or considering neuro axis disorders (also associated with increased kyphosis) in patients with scoliosis. Level II.


In vitro activation of rat brain protein kinase C by polyenoic very-long-chain fatty acids.
A variety of fatty acids including the cis-polyunsaturated very-long-chain fatty acids (VLCFA) (> 22 carbon atoms) common in retina, spermatozoa, and brain were examined for their ability to activate protein kinase C (PKC) purified from rat brain. Arachidonic [20:4(n-6)], eicosapentaenoic [20:5(n-3)], and docosahexaenoic [22:6(n-3)] acids as well as the VLCFA dotriacontatetraenoic [32:4(n-6)] and tetratriacontahexaenoic [34:6(n-3)] were equally capable of activating PKC in vitro with maximal activity being between 25 and 50 microM. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate further enhanced the in vitro activation of PKC when added to the protein kinase assay system with the fatty acids. The fully saturated arachidic acid (20:0) was inactive in both assay systems. The potential significance of the in vitro activation of PKC by the VLCFA is discussed.


Clinical and biochemical characteristics of nonobese type 2 diabetic patients with glutamic acid decarboxylase antibody in Korea.
We evaluated the prevalence of glutamic acid decarboxylase autoantibody (GADA) in nonobese patients with type 2 diabetes mellitus in Korea and investigated the characteristics of GADA-positive and GADA-negative patients. Two years later, we assessed the progression of beta-cell function in these patients. Of the 647 nonobese patients with type 2 diabetes mellitus enrolled in the study, 10.1% was positive for GADA. Glutamic acid decarboxylase antibody-positive patients had lower fasting and stimulated C-peptide levels compared with GADA-negative patients (1.70 +/- 0.72 vs 1.24 +/- 0.59 microg/L, P < .001; 2.59 +/- 1.51 vs 1.99 +/- 0.82 microg/L, P < .001). Patients treated with insulin had lower fasting and stimulated C-peptide levels than those not treated (1.13 +/- 0.52 vs 1.66 +/- 0.73 microg/L, P = .002; 1.85 +/- 0.69 vs 2.49 +/- 0.91 microg/L, P = .004) and had higher titers of GADA (30.5 +/- 7.3 vs 6.0 +/- 4.8 U/mL, P < .001). In terms of progression of beta-cell function, fasting and stimulated C-peptide levels were significantly lower in GADA-positive patients after 2 years (from 1.24 +/- 0.59 to 0.95 +/- 0.54 microg/L, P = .004; from 1.99 +/- 0.82 to 1.61 +/- 0.77 microg/L, P = .007), whereas no such difference was observed in the GADA-negative patients. We demonstrate that a significant proportion of Korean patients may be positive for GADA; this is consistent with studies of white subjects, although disagrees with previous reports on Korean subjects. By assessing the presence of GADA in Korean type 2 diabetic patients, we are able to predict their course of beta-cell function and identify in advance those who are likely to require insulin treatment.


Implications of Stemness Features in 1059 Hepatocellular Carcinoma Patients from Five Cohorts: Prognosis, Treatment Response, and Identification of Potential Compounds.
Cancer stemness has been reported to drive hepatocellular carcinoma (HCC) tumorigenesis and treatment resistance. In this study, five HCC cohorts with 1059 patients were collected to calculate transcriptional stemness indexes (mRNAsi) by the one-class logistic regression machine learning algorithm. In the TCGA-LIHC cohort, we found mRNAsi was an independent prognostic factor, and 626 mRNAsi-related genes were identified by Spearman correlation analysis. The HCC stemness risk model (HSRM) was trained in the TCGA-LIHC cohort and significantly discriminated overall survival in four independent cohorts. HSRM was also significantly associated with transarterial chemoembolization treatment response and rapid tumor growth in HCC patients. Consensus clustering was conducted based on mRNAsi-related genes to divide 1059 patients into two stemness subtypes. On gene set variation analysis, samples of subtype I were found enriched with pathways such as DNA replication and cell cycle, while several liver-specific metabolic pathways were inhibited in these samples. Somatic mutation analysis revealed more frequent mutations of TP53 and RB1 in the subtype I samples. In silico analysis suggested topoisomerase, cyclin-dependent kinase, and histone deacetylase as potential targets to inhibit HCC stemness. In vitro assay showed two predicted compounds, Aminopurvalanol-a and NCH-51, effectively suppressed oncosphere formation and impaired viability of HCC cell lines, which may shed new light on HCC treatment.


Efficient L-Alanine Production by a Thermo-Regulated Switch in Escherichia coli.
L-Alanine has important applications in food, pharmaceutical and veterinary and is used as a substrate for production of engineered thermoplastics. Microbial fermentation could reduce the production cost and promote the application of L-alanine. However, the presence of L-alanine significantly inhibit cell growth rate and cause a decrease in the ultimate L-alanine productivity. For efficient L-alanine production, a thermo-regulated genetic switch was designed to dynamically control the expression of L-alanine dehydrogenase (alaD) from Geobacillus stearothermophilus on the Escherichia coli B0016-060BC chromosome. The optimal cultivation conditions for the genetically switched alanine production using B0016-060BC were the following: an aerobic growth phase at 33 °C with a 1-h thermo-induction at 42 °C followed by an oxygen-limited phase at 42 °C. In a bioreactor experiment using the scaled-up conditions optimized in a shake flask, B0016-060BC accumulated 50.3 g biomass/100 g glucose during the aerobic growth phase and 96 g alanine/100 g glucose during the oxygen-limited phase, respectively. The L-alanine titer reached 120.8 g/l with higher overall and oxygen-limited volumetric productivities of 3.09 and 4.18 g/l h, respectively, using glucose as the sole carbon source. Efficient cell growth and L-alanine production were reached separately, by switching cultivation temperature. The results revealed the application of a thermo-regulated strategy for heterologous metabolic production and pointed to strategies for improving L-alanine production.


3D self-assembled indium sulfide nanoreactor for in-situ surface covalent functionalization: Towards high-performance room-temperature NO2 sensing.
Thiol functionalization of two-dimensional (2D) metal sulfides has been demonstrated as an effective approach to enhance the sensing performances. However, most thiol functionalization is realized by multiple-step approaches in liquid medium and depends on the dispersity of 2D materials. Here, we utilize a three-dimensional (3D) In2S3 nano-porous structure that self-assembled from 2D components as the nanoreactor, in which the surface-absorbed thiol molecules from the chemical residues of the nanoreactor are used for the in-situ covalent functionalization. Such functionalization is realized by facile heat the nanoreactor at 100 °C, leading to the recombing sulfur vacancies with thiol-terminated groups. The NO2 sensing performances of such functionalized nanoreactor are investigated at room temperature, in which In2S3-100 exhibits a response magnitude of 21.5 towards 10 ppm NO2 with full reversibility, high selectivity, and excellent repeatability. Such high-performance gas sensors can be attributed to the additional electrons that transferring from the functional group into the host, thus significantly modifying the electronic band structure. This work provides a guideline for the facile in-situ functionalization of metal sulfides and an efficient strategy for the high performances gas sensors without external stimulus.


Phage-typing of Salmonella weltevreden based on lysogeny. I. The phage-typing system.
All of the 1070 strains of Salmonella weltevreden tested were lysogenic, temperate phage being demonstrable in 83.9% of the strains in broth culture, 6.4% in mixed culture and the remaining 9.7% after induction by UV-irradiation and MC treatment. A phage-typing scheme for Salmonella weltevreden based on the host range of temperate phages was developed. The strains could be classified into eight groups by means of the host range of their temperate phages on six indicator strains and a ninth group, the symbiotic phages of which failed to lyse any of the indicator strains.


17β-Estradiol and 17α-estradiol induce rapid changes in cytoskeletal organization in cultured oligodendrocytes.
Dramatic changes in the cytoskeleton and the morphology of oligodendrocytes (OLs) occur during various stages of the myelination process. OLs in culture produce large membrane sheets containing cytoskeletal veins of microtubules and actin filaments. We recently showed that estrogen receptors (ER) related to ERα/β were expressed in the membrane sheets of mature OLs in culture. Ligation of these or other membrane ERs in OLs with both 17β- and 17α-estradiol mediated rapid non-genomic signaling. Here, we show that estrogens also mediate rapid non-genomic remodeling of the cytoskeleton in mature OLs in culture. 17β-Estradiol caused a rapid loss of microtubules and the actin cytoskeleton in the OL membrane sheets. It also increased phosphorylation of the actin filament-severing protein cofilin, thus inactivating it. Staining for actin barbed ends with rhodamine-actin showed that it decreased the amount of actin barbed ends. 17α-Estradiol, on the other hand, increased the percentage of cells with abundant staining of actin filaments and actin barbed ends, suggesting that it stabilized and/or increased the dynamics of the actin cytoskeleton. The specific ERα and ERβ agonists, 4,4',4″-(4-propyl-(1H)-pyrazole-1,3,5-triyl) trisphenol (PPT) and diarylpropionitrile 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN), respectively, also caused the rapid phosphorylation of cofilin. Estrogen-induced phosphorylation of cofilin was inhibited by Y-27632, a specific inhibitor of the Rho-associated protein serine/threonine kinase (ROCK). The Rho/ROCK/cofilin pathway is therefore implicated in actin rearrangement via estrogen ligation of membrane ERs, which may include forms of ERα and ERβ. These results indicate a role for estrogens in modulation of the cytoskeleton in mature OLs, and thus in various processes required for myelinogenesis.


99mTc-human immunoglobulin (HIG)--first results of a new agent for the localization of infection and inflammation.
Technetium (99mTc) labelled, polyclonal human immunoglobulin (HIG) is a new agent that detects focal infection and inflammation. This new agent was compared in 40 patients with the accepted standard, namely 111In-oxine-labelled leucocytes. This comparison resulted in a sensitivity of 94% and a specificity of 96% for 99mTc-HIG when 111In-oxine leucocytes were defined as giving the true result. The new agent was shown to localize both sepsis and active inflammatory bowel disease (IBD). There was 100% concordance in the 16 patients with IBD who were imaged with both 99mTc-HIG and 111In-oxine leucocytes. Discordant results were obtained in one case of suspected osteomyelitis, which was false-positive on the 99mTc-HIG scan, and one case of pyrexia of unknown origin when the 99mTc-HIG was false-negative and the 111In-oxine leucocyte scan demonstrated accumulation of tracer in the caecum at 24 h post-injection. Normal distribution for 99mTc-HIG demonstrated activity in the kidneys and bladder and that 50% of the tracer is cleared through the kidneys during the first 24 h post-injection. There were no major or minor side-effects.


Corrigendum to: IDH knockdown alters foraging behavior in the termite Odontotermes formosanus in different social contexts.
[This corrects the article DOI: 10.1093/cz/zoab032.].


Propagation of amygdala-kindled seizures to the hippocampus in the rat: electroencephalographic features and behavioural correlates.
The propagation of amygdala-kindled seizures to the dorsal and ventral hippocampus was examined, in rats. The relation of contralateral seizure propagation to the onset of generalized convulsions was also studied. In all subjects, electrodes were implanted in the amygdala. Two additional electrodes were implanted (bilaterally) in the dorsal (n = 6) or ventral (n = 8) hippocampus. Kindling stimulations were delivered twice daily (interval 4 h). Initially, triggered after-discharges (ADs) were recorded only in the amygdala. With repeated stimulation, the AD propagated to the hippocampus. Rates of propagation were as follows (mean # of stimulations +/- SEM): ipsilateral ventral hippocampus, 4.0 +/- 0.9; ipsilateral dorsal hippocampus, 6.2 +/- 1.4; contralateral dorsal hippocampus, 7.5 +/- 1.4; contralateral ventral hippocampus, 8.5 +/- 1.0. AD propagation to contralateral sites was significantly slower than to ipsilateral sites. Ipsilateral hippocampal recruitment occurred between stages 1 and 2 (partial seizures), whereas contralateral hippocampal recruitment occurred between stages 2 and 3 (transition to generalized seizures). These results indicate that during amygdala-kindling, it takes several stimulations before discharge propagates to the hippocampus. The close link between contralateral hippocampus involvement and seizure generalization warrants further study, and may lead to a better understanding of the pathways involved in seizure spread.


M-phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl-2 and EMT-related signaling pathways.
The main issue of this study is to demonstrate whether M-phase phosphoprotein 8 (MPP8) affect gastric tumor growth and metastasis. Retrospective study was proceeded in 280 patients' surgical specimens with different disease stages. Loss-of-function assays, including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, flow cytometry, and transwell assays were performed to evaluate the biological function of MPP8 in gastric cancer cells. Apoptosis and metastasis relative biomarkers were measured by quantitative real-time polymerase chain reaction and Western blot analysis. Compared with normal adjacent tissues, obviously elevated MPP8 expression was found in gastric cancer tissues. Elevated MPP8 expression was associated with male sex (vs female sex), intermediate differentiation (vs poorly differentiated cancer), and later stage (vs earlier stage). Furthermore, MPP8 overexpression in tumor tissues was marginally associated with a poor prognosis, with a significant relationship between MPP8 overexpression and prognosis among patients with poorly differentiated gastric cancer. Inhibition of MPP8 in these cells significantly suppressed proliferation and colony formation, promoted apoptosis, and repressed invasion. Furthermore, silencing of MPP8 remarkably increased apoptosis-related proteins (p53, Bax, and PARP) expression, but downregulated Bcl-2 expression. Silencing of MPP8 also decreased the expression of metastasis pathway-related proteins (N-cadherin and vimentin), and as well as the levels of anti-oncogene ZEB1, MET, and KRAS mRNA. Our findings demonstrated that MPP8 might be an oncogene by positively regulating gastric cancer cell function through the p53/Bcl-2 and epithelial to mesenchymal transition-related signaling pathways.


Carmustine wafer implantation for supratentorial glioblastomas, IDH-wildtype in "extreme" neurosurgical conditions.
We assessed the feasibility of Carmustine wafer implantation in "extreme" conditions (i.e. patients > 80 years and Karnofsky Performance Status score < 50) and of implantation ≥ 12 Carmustine wafers in adult patients harbouring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. We performed an observational, retrospective single-centre cohort study at a tertiary surgical neuro-oncological centre between January 2006 and December 2021. Four hundred eighty patients who benefited from a surgical resection at first-line treatment were included. We showed that Carmustine wafer implantation in patients > 80 years, in patients with a Karnofsky performance status score < 50, and that implantation ≥ 12 Carmustine wafers (1) did not increase overall postoperative complication rates, (2) did not affect the completion of standard radiochemotherapy protocol, (3) did not worsen the postoperative Karnofsky Performance Status scores, and (4) did not significantly affect the time to oncological treatment. We showed that the implantation of ≥ 12 Carmustine wafers improved progression-free survival (31.0 versus 10.0 months, p = 0.025) and overall survival (39.0 versus 16.5 months, p = 0.041) without increasing postoperative complication rates. Carmustine wafer implantation during the surgical resection of a newly diagnosed supratentorial glioblastoma, IDH-wildtype is safe and efficient in patients > 80 years and in patients with preoperative Karnofsky Performance Status score < 50. The number of Carmustine wafers should be adapted (up to 16 in our experience) to the resection cavity to improve survival without increasing postoperative overall complication rates.


The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy.
Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman's capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman's capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.


Effect of temperature-sensitive mutation on activity of the RNA transcriptase of vesicular stomatitis virus New Jersey.
The virion-associated RNA transcriptase activity of vesicular stomatitis virus New Jersey temperature-sensitive (ts) mutants was assayed in vitro at the permissive (31 degrees C) and restrictive (39 degrees C) temperatures. RNA synthesis at 39 degrees C by the RNA-negative ts A1 and the RNA-positive ts C1 and ts D1 mutants was similar to that of wild-type virus. The RNA-negative ts B1 synthesized only small amounts of RNA in vitro at 39 degrees C. The three mutants of complementation group E were dissimilar in the amounts of RNA they synthesized at 39 degrees C: ts E1 synthesized very little RNA, ts E2 synthesized moderate amounts, and RNA synthesis by ts E3 was not inhibited. The two mutants of group F were also dissimilar, since ts F1 synthesized very little RNA at 39 degrees C, whereas ts F2 synthesized as much RNA as wild-type virus. The revertant clones ts B1/R1, ts E1/R1, and ts F1/R1 synthesized RNA at 39 degrees C in amounts comparable to wild-type virus, indicating that the heat sensitivity of the transcriptase activity of the mutants ts B1, ts E1, and ts F1 was associated with temperature sensitivity. Similar heat sensitivities were observed when transcribing nucleoprotein complexes were used in the assays, showing that the mutated polypeptides were part of the viral core. The heat stability of the mutant ts B1 was similar to that of wild-type virus, and in vitro RNA synthesis was fully restored when the temperature was lowered to 31 degrees C after 30 min of preincubation at 39 degrees C, showing that the inhibition was due to reversible configurational change of the mutated polypeptide. When virions of the mutant ts E1 were heated for 5 h at 39 degrees C, their infectivity and transcriptase activity were as stable as those of the wild-type virus, whereas transcriptase activity became very heat labile after disruption of the viral coat with a neutral detergent. This suggests an interaction between the mutated polypeptide and a coat polypeptide which stabilizes the activity of the transcriptase. The RNA transcriptase activity of the mutant ts F1 was also heat labile, although to a lesser extent than that of ts E1. Thus, the defects in transcriptase activity of groups B, E, and F suggest that all three polypeptides of the virus core, polypeptides L, N, and NS, are involved in the transcription. In addition, we postulate that the mutated gene products of groups E and F are multifunctional, being required both in transcription and replication, and that the gene product of group E may also be involved in some late stage of virus development.


An 18-months' evaluation of self-etch and etch & rinse adhesive in non-carious cervical lesions.
In this intra-individual comparison (an 18-months' randomized, controlled prospective study), we evaluated the clinical performance of one self-etch and one "etch & rinse" adhesive in non-carious cervical lesions. Twenty-five patients with at least two pairs of similar-sized non-carious cervical lesions participated. Seventy-eight restorations were placed; 39 with etch & rinse (Single-Bond) and 39 with self-etch (Adper Prompt). Both adhesives were combined with the microfilled resin composite Filtek-A110. The restorations were evaluated at baseline, 6, 12, and 18 months according to slightly modified USPHS criteria. Statistical differences between the adhesives was tested with McNemar's test and clinical degradation over time for each material with the Fisher exact test (a=0.05). Thirty pairs were evaluated at 12 and 18 months. Two self-etch restorations were lost after 18 months. Nine Adper Prompt and four Single-Bond restorations scored bravo for marginal adaptation at 18 months (p<0.05). Nine Adper Prompt and three Single-Bond restorations scored bravo for marginal discoloration (p<0.05). Both adhesive systems showed acceptable clinical retention rates according to the ADA full acceptance criteria for enamel-bonding systems in class V non-carious lesions. The self-etch adhesive showed a faster progressive marginal degradation.


Modulation of therapeutic sensitivity by human papillomavirus.
Human papillomaviruses (HPVs) are small double-stranded DNA viruses that pose significant public health concerns as the causative agent of approximately 5% of worldwide cancers. The HPV oncogenes E6 and E7 play key roles in carcinogenesis. In the last 15years there has been a significant increase in the incidence of HPV-related head and neck cancers arising primarily in the oropharynx. Patients with HPV-positive head and neck cancers (HNCs) have a significantly improved prognosis compared to those with HPV-negative disease. In this review we will discuss data suggesting how HPV oncogenes modulate both the intrinsic radiation sensitivity of HNCs and also have important effects upon the tumor microenvironment. Together, these findings contribute to the improved outcomes seen in patients with HPV-positive HNC.


Impact of COVID-19 on emergency department visits among palliative home care recipients: a retrospective population-based cohort study in the Piedmont region, Italy.
Integrated palliative home care (IHPC) is delivered to patients with progressive end-stage diseases. During the COVID-19 pandemic, IHPC needed to provide high-quality home care services for patients who were treated at home, with the goal of avoiding unnecessary care, hospital admissions, and emergency department (ED) visits. This study aimed to compare the ED visits of IHPC recipients in a large Italian region before and during the first two waves of the COVID-19 pandemic and to find sociodemographic or clinical characteristics associated with changes in ED visits during the first two waves of COVID-19 pandemic, compared with the period before. Administrative databases were used to identify sociodemographic and clinical variables of IHPC recipients admitted before and during the pandemic. The obtained data were balanced by applying a propensity score. The average number of ED visits before and during the pandemic was calculated by using the Welch's t test and stratified by all the variables. Before and during the pandemic, 5155 and 3177 recipients were admitted to IHPC, respectively. These individuals were primarily affected by neoplasms. ED visits of IHPC recipients reduced from 1346 to 467 before and during the pandemic, respectively. A reduced mortality among IHCP patients who had at least one ED visit during the pandemic (8% during the pandemic versus 15% before the pandemic) was found. The average number of ED visits decreased during the pandemic [0.143, confidence interval (CI) = (0.128-0.158) versus 0.264, CI = (0.242-0.286) before the pandemic; p < 0.001] for all ages and IHPC duration classes. The presence of a formal caregiver led to a significant decrease in ED use. Medium and high emergency ED admissions showed no difference, whereas a decrease in low-level emergency ED admissions during the pandemic [1.27, CI = (1.194-1.345) versus 1.439, CI = (1.3-1.579) before the pandemic; p = 0.036] was found. ED visits among IHPC recipients were significantly decreased during the first two waves of the COVID-19 pandemic, especially in those individuals characterized by a low level of emergency. This did not result in an increase in mortality among IHPC recipients. These findings could inform the reorganization of home care services after the pandemic.


Angiotensin II induces endothelin-1 expression in human hepatic stellate cells.
Both angiotensin (Ang)-II and endothelin-1 (ET-1) are involved in the pathogenesis of liver fibrosis. Activated hepatic stellate cells (HSCs) are considered a key effector of liver fibrosis. To explore the effect of Ang-II on ET-1 expression in cultured human HSCs and the underlying mechanisms. Human HSCs were treated with Ang-II in different concentrations (0.1, 0.5, 1, 5, or 10 nM) for different lengths of time (0.5, 1, 2, 4, or 6 h) with or without transcription inhibitor actinomycin D, Ang-II type 1 (AT1) receptor blocker losartan, AT2 receptor blocker PD123177, or different kinase inhibitors. Ang-II increased the ET-1 mRNA level in a statistically significant dose- and time-dependent manner within 4 h, which led to dose-dependent up-regulation of the ET-1 protein level. Actinomycin D (1 mg/ml), losartan (50 μM), and phosphatidylinositol-3 kinase inhibitor LY294002 (50 μM) abolished the promoting effect of Ang-II on ET-1 expression. Ang-II (10 nM) significantly increased the expression of α-smooth muscle actin and type I collagen in HSCs, which was abolished by losartan, LY294002, ET A receptor blocker BQ123, and ET-1 siRNA, but not PD123177 and ET B receptor blocker BQ788. Ang-II induces ET-1 expression in human HSCs via the AT1 receptor by the PI3 K/Akt signaling pathway. The ET-1/ET A receptor axis could mediate the promoting effects of Ang-II on HSCs' transdifferentiation into myofibroblast-like cells. This is the first evidence of crosstalk between the Ang-II/AT1 axis and the ET-1 system in regard to the pathogenesis of liver fibrosis.


Molecular spectrum of beta-thalassemia mutations in Northwestern Iran.
Beta-thalassemia (beta-thal) is a hereditary autosomal disorder with decreased or absent beta-globin chain synthesis. This study was designed to identify the common and rare beta-thal mutations in the Azerbaijan provinces, Northwestern Iran, and to set up a prenatal diagnostic laboratory. One hundred unrelated patients with known beta-thal major and intermedia, registered with the thalassemia clinics in the provincial capitals of Tabriz and Ardebil, were included. Mutations were studied in 200 chromosomes, by polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) and direct sequencing methods. We found 17 beta-thal mutations in this region of Iran. The results showed that IVS-II-1 (-->GA) was the most frequent mutation, comprising 21% of all mutations. Other common mutations were IVS-I-110 (-->GA) 18%, frameshift codons (FSC) 8/9 (+G) 14.5%, FSC 8 (-AA) 8% and IVS-I-1 (GA) 7.5%. This is the first comprehensive study in this region and could be useful for developing a beta-thal molecular screening in Azerbaijan-Iran.


The influence of social environment on endocrine, cardiovascular and tissue responses in the rabbit.
Previous work from our lab demonstrated that social environment influences the progression of atherosclerosis in genetically hyperlipidemic rabbits. The purpose of the current study was to examine behavioral and physiological responses associated with these distinct chronic social conditions. Normolipidemic rabbits were exposed to one of three social environments for 4 hours/day over 20 weeks: 1) an Unstable Group in which animals were paired weekly with a different unfamiliar rabbit, 2) a Stable Group in which rabbits were paired with the same littermate for the entire study, and 3) an Individually Caged Group in which animals were socially isolated. It was found that the Unstable Group, characterized by increased agonistic behavior and relatively less affiliative behavior, exhibited physiological responses indicative of chronic stress (increased urinary norepinephrine, plasma cortisol, splenic weight, and decreased visceral fat and body weight compared to the other groups). These animals also had increased acute plasma oxytocin responses relative to the other groups 10 minutes into the social pairing. In contrast, the Stable Group exhibited more affiliative behavior and less stressful physiological and tissue responses. The Individually Caged Group had elevated urinary norepinephrine relative to the Stable Group, and they exhibited higher heart rates at the end of the study compared to the other groups, suggesting that this social environment is also associated with chronic sympathetic arousal. It was concluded that distinct social contexts lead to different patterns of behavioral and physiological responses, and these responses are relevant to the pathophysiology of atherosclerosis and cardiovascular disease.


The influence of the route of administration of gold nanoparticles on their tissue distribution and basic biochemical parameters: In vivo studies.
The gold nanoparticles (AuNP's) exhibit interesting chemical and physical properties and for this reason are intensively tested in medicine. However there is a lack of information about toxicity of those nanoparticles as well as their excretion from the body. Thus, the aim of the present study was to investigate the influence of the route of administration of gold nanoparticles to rats on their distribution in tissues and excretion rate. The experiment was carried out on male Wistar rats. The colloidal gold suspension containing 0.3619 mg of particles per milliliter, was administered per 1 kg of body weight. Serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, glucose and ferric reducing ability of plasma were measured in all investigated animals. It was shown that after oral administration only a small amount of AuNPs was absorbed. In addition, excretion of the metal during consecutive days after po or iv administration was examined. Moreover, the impact of AuNPs on some biochemical parameters 3 days after intravenous administration was studied. It was shown that the AuNPs are mainly cumulated in the liver, lungs and in spleen after iv administration and only slightly removed from the body in urine and feces. Accumulation of those nanoparticles effect in increases of FRAP and glucose level up to 27% and 73%, respectively. This in turn suggests that iv administration of AuNPs may effect in serious medical complications. On the other site, the accumulation in the liver of about 50% of introduced particles to the rats body is promising for phototherapy and it opens "door" for drug transport to this organ.


Passive cooling to initiate hypothermia for transported encephalopathic newborns.
Two newborns at high risk for severe encephalopathy were passively cooled by discontinuing the supplied heat from a radiant warmer. Cooling was attempted in both babies (successfully in one) before the arrival of the neonatal transport team. Both infants had core temperatures of approximately 34 degrees C on arrival at the NICU. Passive cooling may be an effective method to initiate cooling very early in the course of encephalopathy.


Stabilization of black rice anthocyanins by self-assembled silk fibroin nanofibrils: Morphology, spectroscopy and thermal protection.
Nanofibrillated proteins possess diverse techno-functional properties are considered as matrices for stabilizing bioactive agents. In this study, the morphology and interaction of silk fibroin nanofibrils (SNFs) with black rice anthocyanins (ACN) were investigated through multiple microscopy and spectroscopic techniques. The impact of SNFs on the thermal stability of ACN was analyzed. Nanofibrils with diameter less than 20 nm were self-assembled from silk fibroin (SF) lyophilized powder solution at pH 6.0. A static model occurred in the interactions of cyanidin-3-O-glucoside (C3G, the major anthocyanin in black rice) with SF and SNFs. C3G binding altered the secondary structures of SF and SNFs. Moreover, the thermal retention rates of ACN combined with SF and SNFs were significantly (P < 0.05) higher than that of ACN alone followed the order of SNFs-ACN (60.87%) > SF-ACN (57.47%) > ACN alone (40.33%) after heating 120 min at 80 °C and SNFs-ACN (50.42%) > SF-ACN (32.81%) > ACN alone (23.64%) after heating 120 min at 90 °C. The half-life (t1/2) of thermal degradation of ACN was elongated in SNFs-ACN complex compared with that in SF-ACN complex. These results showed that SNFs effectively binding with C3G and exhibit better protective effects on the thermal stability of ACN than SF.


Home-hospital care for children with acute illnesses: A 2-year follow-up study.
Procedures normally performed in the hospital setting are increasingly delivered as part of hospital at home (HAH) programmes. The aim of this study is to describe the procedures and diseases treated during the first 2 years of a new paediatric HAH programme. This is a retrospective, observational study conducted in the HAH programme of Niño Jesús Children's Hospital (Spain). We included demographic data, diagnosis and procedures delivered to patients admitted to the HAH programme from November 2018 to November 2020. There were 935 admissions of 833 patients. The median age was 5 years (interquartile range 2.3-9.5). Seventy-five percent of patients were previously healthy. The most frequent illnesses were acute infections (37%) (e.g. complicated appendicitis and ENT, genitourinary, skin and soft tissue infections) and acute respiratory diseases (17.3%) (e.g. asthma, bronchiolitis and pneumonia). Thirty-six percent of admissions underwent nocturnal polysomnography. The median length of stay was 4 days (SD 4.9 days). Eight percent of the episodes studied required care in the emergency department due to condition worsening (55.3%) and problems with devices (36.1%). Hospital readmission was required in 5.6% of cases, 42.4% of which later resumed care in the HAH. The estimated daily cost of HAH is 330.65 euros, while the hospital per-day costs of polysomnography, asthma and endovenous therapy are 1899.24, 1402.5, and 976.26 euros. Ninety percent of families reported a high level of satisfaction. Paediatric HAH programmes are a feasible, cost-effective alternative to hospital care. Further studies should compare the evolution of patients treated in the traditional hospital setting and those in HAH.


Temperature effects on tubificid worms and their relation to sediment oxygen demand.
Sediment samples were collected from the Dead River in New Jersey and tested in the laboratory under two temperature conditions, 4 degrees C and 20 degrees C. The study was conducted to determine the effect of worm density on the sediment oxygen demand (SOD) rate and if temperature affects the ability for tubificid worms to deplete dissolved oxygen (DO) from the overlying stream water. The study showed that the DO concentration was affected by tubificid worm density and that higher temperature increased the metabolic activity of the worms.


Frailty: A Multidimensional Biopsychosocial Syndrome.
The original conceptual landscape of frailty has evolved into a complex, multidimensional biopsychosocial syndrome. This has broadened the field to now include social and behavioral scientists and clinicians from a wide range of specialties. This article aims to provide an updated overview of this conceptual change by examining the emerging definitions of physical, cognitive, social, and psychological frailty; the tools used for diagnosis and assessment of these domains; the epidemiology of the domains; their pathogenesis, risk factors, and course; frameworks for prevention and treatment; and unresolved issues affecting the field.


Prevalence of Overt and Occult Hepatitis B Virus Infection among HIV-Positive People Referring to Consultation Center for Behavioral Diseases, Kurdistan Province, Iran
Based on evidence, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) have common transmission routes; co-infection of HBV/HIV can dramatically increase disease progression. The present study aimed to determine the prevalence of overt HBV infection and occult hepatitis B virus infection (OBI) in HIV-positive people. In this descriptive study, whole blood samples were collected from 184 HIV-positive subjects referring to the Consultation Center for Behavioral Diseases, Sanandaj, Iran, during 2014 to 2016. ELISA was used for the determination of HBV serologic markers (hepatitis B surface antigen [HBsAg] and antibodies to hepatitis B virus core antigen [anti-HBc]). To evaluate OBI, DNA was extracted only from HBsAg-negative and anti-HBc-positive samples and tested for HBV DNA by real-time PCR. Test results and patients' data were analyzed by SPSS software. The mean age of the study population was 39.2 ± 9.4 (SD) years, of whom 140 (76%) were male. Overall, 43 (23.3%) samples were positive for HBsAg (overt HBV infection), and 50 (27.2%) for anti-HBc. Among 31 HBsAg-negative and anti-HBc-positive samples (suspected OBI), one (3.2%) sample was positive for HBV DNA (verified seropositive OBI). HBV infection was higher among males (n = 37; 86.05%), jobless people (n = 23; 53.49%), and those with an injection HIV transmission route (n = 32; 74.43%). We observed a high prevalence of overt HBV and one OBI among the study population. A serologic marker such as anti-HBc indicates resolved or past HBV infection. Molecular screening for HBV is valuable for the management of HIV-infected people.


Surgically Relevant Morphological Parameters of Proximal Human Femur: A Statistical Analysis Based on 3D Reconstruction of CT Data.
Recently, more accurate description of the femoral geometry has become of interest to engineers and orthopedic surgeons. However, an appropriate database is lacking. Therefore, the aim of this study is to present morphological parameters and their correlations, which are relevant for medical issues such as impingement after total hip replacement, as well as for implant design and the etiology of hip fractures. We investigated 12 well-known morphological parameters of the femur in 169 healthy human subjects through evaluation of 3D-reconstructed CT scans. Pearson's coefficients of correlations were calculated using a statistical t-test method for each pair of parameters. The mean, maximum, minimum, median, and standard deviation values are reported for all parameters. Histograms showing the distribution of each morphological parameter are also presented. It is shown that absolute and horizontal offsets, total femur length, and NCVD parameters are normally distributed, but NCDF and NCDS are not. Furthermore, an inter-correlation matrix was reported to reveal statistical correlations between these parameters. The strongest positive correlation existed between absolute offset (OSA) and horizontal offset (OSH), while the least positive correlation was found between NCDF and total femur length (TFL), and also between NCDS and NCDF. Anteversion angle (ATA) and OSA showed the least negative correlation. However, the strongest negative correlation was found between neck-shaft angle (NSA) and greater trochanter height (GTH), as well as between OSA and NCVD. Comprehending patients' native bone morphology, including the variations and correlations, is essential for orthopedic surgeons to undertake preoperative planning and surgery as well as to appropriately design medical devices. Thus, more population-based detailed databases are necessary. We investigated an extensive set of proximal femoral morphology parameters using a statistically standardized method to expand the existing knowledge. The results of our study can be used for diverse medical and biomechanical purposes.


Molecular evidence for high frequency of multiple paternity in a freshwater shrimp species Caridina ensifera.
Molecular genetic analyses of parentage provide insights into mating systems. Although there are 22,000 members in Malacostraca, not much has been known about mating systems in Malacostraca. The freshwater shrimp Caridina ensifera blue, is a new species belonging to Malacostraca which was discovered recently in Sulawesi, Indonesia. Due to its small body size and low fecundity, this species is an ideal species to study the occurrence and frequency of multiple paternity and to understand of how the low fecundity species persist and evolve. In this study, we developed four polymorphic microsatellites from C. ensifera and applied them to investigate the occurrence and frequency of multiple paternity in 20 C. ensifera broods caught from Lake Matano, Sulawesi. By genotyping the mother and all offspring from each brood we discovered multiple paternity in all 20 broods. In most of the 20 broods, fathers contributed skewed numbers of offspring and there was an apparent inverse correlation between reproductive success of sires and their relatedness to mothers. Our results in combination with recent reports on multiple paternity in crayfish, crab and lobster species suggests that multiple paternity is common in Malacostraca. Skewed contribution of fathers to the numbers of offspring and inverse correlation between reproductive success of sires and their relatedness to mothers suggest that sperm competition occurred and/or pre- and postcopulatory female choice happen, which may be important for avoiding the occurrence of inbreeding and optimize genetic variation in offspring and for persistence and evolution of low fecundity species.


Infrainguinal Vein Graft Stenoses: Long-Term Outcomes of Graft Angioplasty.
Graft angioplasty combines the durability and ability of surgical bypasses to treat long arterial occlusions with the minimally invasive nature of endovascular procedures. The purpose of this study was to evaluate the efficacy of single and repeated graft angioplasty in revising failing infrainguinal vein bypass grafts and to determine predictors of medium- and long-term freedom from revision after graft angioplasty. This was a retrospective analysis from a prospectively maintained database. Consecutive endovascular revisions of graft-threatening lesions identified by duplex ultrasound surveillance were reviewed from 2003 to 2010. Patients were followed up until death, major amputation, or the end of follow-up, with the data last updated on January 1, 2013. 178 graft angioplasty procedures performed in 114 bypass grafts in 103 limbs from 98 patients were studied. At 5 years, freedom from revision was 22.6%, graft survival was 45.8%, amputation-free survival was 57.9%, and patient survival was 64.9%. Analysis of repeated angioplasties found no evidence that effectiveness diminishes significantly with the number of previous angioplasties performed (p=.892). Higher Rutherford Grade of ischemia and longer time interval from index surgery to first angioplasty were significant positive predictors of medium- and long-term patency. Percutaneous transluminal angioplasty of infrainguinal vein grafts is safe and effective in the treatment of failing grafts identified by duplex surveillance. Graft angioplasties do not lose effectiveness when repeated and have shown cumulative benefit in prolonging graft survival. Treatment of claudicants and time interval from graft implantation of more than 6 months at the time of first angioplasty are positive predictors of at least medium-term patency after graft angioplasty.


Synthesis and in vitro evaluation of a library of modified endomorphin 1 peptides.
Endomorphin 1 (Endo-1=Tyr-Pro-Trp-Phe-NH(2)), an endogenous opioid with high affinity and selectivity for mu-opioid receptors, mediates acute and neuropathic pain in rodents. To overcome metabolic instability and poor membrane permeability, the N- and C-termini of Endo-1 were modified by lipoamino acids (Laa) and/or sugars, and 2',6'-dimethyltyrosine (Dmt) replacement of Tyr. Analogues were assessed for mu-opioid receptor affinity, inhibition of cAMP accumulation, enzymatic stability, and permeability across Caco-2 cell monolayers. C-terminus modification decreased receptor affinity, while N-terminus C8-Laa improved stability and permeability with slight change in receptor affinity. Dmt provided a promising lead compound: [C8Laa-Dmt[1]]-Endo-1 is nine times more stable (t(1/2)=43.5min), >8-fold more permeable in Caco-2 cell monolayers, and exhibits 140-fold greater mu-opioid receptor affinity (K(imu)=0.08nM).


[Reflections on the biosynthesis of morphine and idiopathic Parkinson's disease].
Based on a day-by-day, in-depth study of a clinical case, it was deduced that Parkinson's disease results in autointoxication, due to damage to morphine biosynthesis. Blood morphine levels should be studied in patients suffering from Parkinson's disease before treatment as well as in depressive patients (being the group most affected by Parkinson s disease) to achieve early preclinical diagnosis.


Metachronous lesions after gastric endoscopic submucosal dissection: first assessment of the FAMISH prediction score.
Surveillance after gastric endoscopic submucosal dissection (ESD) is recommended for all patients owing to the persistent risk of metachronous gastric lesions (MGLs). We developed and validated a prediction score to estimate MGL risk after ESD for early neoplastic gastric lesions, to define an individualized and cost-saving approach. Clinical predictors and a risk score were derived from meta-analysis data. A retrospective, single-center, cohort study including patients with ≥ 3 years of standardized surveillance after ESD was conducted for score validation. Predictive accuracy of the score by the area under the receiver operating characteristic curve (AUC) was assessed and cumulative probabilities of MGL were estimated. The risk score (0-9 points) included six clinical predictors (scored 0-3): positive family history of gastric cancer, older age, male sex, corpus intestinal metaplasia, synchronous gastric lesions, and persistent Helicobacter pylori infection (FAMISH). The study population included 263 patients. The MGL rate was 16 %. The score diagnostic accuracy for predicting MGL at 3 years' follow-up, measured by the AUC, was 0.704 (95 %CI 0.603-0.806). At 3 years and a cutoff < 2, the score achieved maximal sensitivity and negative predictive value; 15 % of patients could be assigned to a low-risk group, in which the progression to MGL was significantly lower than for the high-risk group (P = 0.04). The FAMISH score might be a useful tool to accurately identify patients with low-to-intermediate risk for MGL at 3 years of follow-up who could have surveillance intervals extended to reduce the burden of care.


Rise of levels of von Willebrand factor and factor VIII with age: Role of genetic and acquired risk factors.
Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels. To disentangle the role of genetic (sex, blood group) and acquired factors (comorbidities, body mass index, reduced kidney function, hormone use, and inflammation) in regulating von Willebrand factor antigen (VWF:Ag) and factor VIII activity (FVIII:C) levels in the normal population. Analysis were performed in a large population sample (2923 individuals) from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), after exclusion of individuals with active cancer and women who were pregnant or within nine months postpartum. The increase of VWF:Ag and FVIII:C with age was evaluated by linear regression after the age of 40 years. Analyses were adjusted for acquired factors and stratified for sex and blood group. VWF:Ag and FVIII:C increased with age: increase per decade of age for VWF:Ag 18 IU/dL (95%CI 15-20) and for FVIII:C 12 IU/dL (95%CI 10-14). After adjustment for acquired factors, the increase per decade was 13 IU/dL (95%CI 10-16) for VWF:Ag and 9 IU/dL (95%CI 6-11) for FVIII:C. The stratified analysis for blood group showed higher increase in the non-O group, but these differences were annulled after adjustment for acquired factors. VWF:Ag and FVIII:C increase with age. Carriers of blood group non-O present a steeper increase of VWF:Ag and FVIII:C with age, that is mediated by acquired factors.