Preliminary biochemical characterization of faeces from uninfected rats and rats infected with the tapeworm, Hymenolepis diminuta.
Faecal pellets were collected from uninfected rats and rats infected with Hymenolepis diminuta, and analysed for caloric value, lipids, carbohydrates, glucose, amino acids, and proteins. Faeces from infected rats contained significantly more lipid and less carbohydrate and glucose than faeces from control rats. The total free amino acid content of faeces from infected and control rats did not differ, but there were significant differences in the amounts of individual free amino acids. The data support the hypothesis that the nutrient composition of faeces from infected and control hosts differ. Beetles that serve as the intermediate host for H. diminuta may be able to detect these differences, and this may explain why beetles preferentially ingest faeces containing the tapeworm s eggs.


Establishment and characterization of a human cholangiocarcinoma cell line.
Cholangiocarcinoma (CC) is a rare malignant tumor arising from the biliary tract. The disease is notoriously difficult to diagnose and is usually fatal due to its late clinical presentation and the lack of effective non-surgical therapeutic strategies. To date, little is known about the cancer biology of the disease and the establishment and characterization of only a few CC cell lines have been reported. We report here the establishment of a new human cancer cell line, HKGZ-CC, from a moderate to poorly differentiated intrahepatic bile duct carcinoma from a Chinese patient. Morphological characteristics, growth kinetics, ability to grow on anchorage-independent soft agar, tumorigenicity in nude mice and cytogenetic features of the cell line were investigated. Chromosome banding karyotype and comparative genomic hybridization analyses revealed chromosomal changes in 1pter-p31, 1q31-qter, 3q, 8q21-qter, 9pter-9q34, 10, 13q21-qter and X. This newly established cell line should serve as a useful model for studying the molecular pathogenesis of CC.


Evolution of substrate specificity in a retained enzyme driven by gene loss.
The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.


'No touch' technique for coronary anastomoses with arterial grafts.
We describe a simple no-touch technique for facilitating coronary anastomosis using different arterial grafts. To accomplish this technique it is necessary to make a cut near the end of the graft creating a "cuff". Holding this cuff during the anastomosis steadies the graft, which simplifies the suturing technique and facilitates precise anastomosis.


Thalamic midline cell populations projecting to the nucleus accumbens, amygdala, and hippocampus in the rat.
The organization of the thalamic midline efferents to the amygdaloid complex, hippocampal formation, and nucleus accumbens was investigated in the rat by means of multiple retrograde fluorescent tracing. The present findings indicate that these connections derive from separate cell populations of the thalamic midline, with a low degree of divergent collateralization upon more than one of the targets examined. The neural populations projecting to the amygdala, hippocampus, or accumbens are highly intermingled throughout the thalamic midline, but display some topographical prevalence. Midline thalamo-hippocampal cells are concentrated in the nucleus reuniens; thalamo-accumbens neurons prevail in the ventral portion of the paraventricular nucleus, and in the central medial nucleus. Thalamo-amygdaloid cells display a topographical prevalence in the rostral third of the thalamic midline and are concentrated in the dorsal part of the paraventricular nucleus and in the medial part of the nucleus reuniens. Both dorsally in the paraventricular nucleus and ventrally in the nucleus reuniens, thalamo-amygdaloid cells are located closer to the ependymal lining than the neurons projecting to the hippocampus or nucleus accumbens. Further, thalamo-amygdaloid cells, especially in the paraventricular nucleus, extend their dendritic processes in the vicinity of the ependymal lining, where they arborize profusely. These features indicate a close topographical relationship of neurons projecting to the amygdala with ependymal cells. The fairly discrete origin of midline outputs to the amygdala, hippocampus, and accumbens indicates that the flow of information is conveyed through separate channels from the thalamic midline to limbic and limbic-related targets. Together with the literature on the limbic afferents to the thalamus, these findings emphasize the relationships between the thalamus and the limbic system subserved by parallel input-output routes. However, because of the overlap of the projection cell populations, the thalamic midline may represent a locus of interaction among neurons connected with different parts of the limbic system. The functional implications of these findings are discussed in relation to the "nonspecific" thalamic system, as well as to the circuits involved in memory formation.


SGT1 interacts with the Prf resistance protein and is required for Prf accumulation and Prf-mediated defense signaling.
The highly conserved eukaryotic co-chaperone SGT1 (suppressor of the G2 allele of skp1) is an important signaling component of plant defense responses and positively regulates disease resistance conferred by many resistance (R) proteins. In this study, we investigated the contribution of SGT1 in the Prf-mediated defense responses in both Nicotiana benthamiana and tomato (Solanum lycopersicum). SGT1 was demonstrated to interact with Prf in plant cells by co-immunoprecipitation. The requirement of SGT1 in the accumulation of Prf or autoactive Prf(D1416V) was determined by the degradation of these proteins in N. benthamiana, in which SGT1 was repressed by virus-induced gene silencing (VIGS). Pseudomonas pathogen assay on the SGT1-silenced tomato plants implicates SGT1 is required for the Prf-mediated full resistance to Pseudomonas syringae pv. tomato (Pst). These results suggest that, in both N. benthamiana and tomato, SGT1 contributes to the Prf-mediated defense responses by stabilizing Prf protein via its co-chaperone activity.


Morning glory disc anomaly and its implications in moyamoya arteriopathy: a retrospective case series.
Morning glory disc anomaly (MGDA), a congenital abnormality of the optic nerve, may be associated with moyamoya arteriopathy, a cerebrovascular abnormality. In this study, the authors aimed to define the temporal evolution of cerebrovascular arteriopathy in patients with MGDA to characterize a rational strategy for screening and management over time. The records of pediatric neurosurgical patients at two academic institutions were retrospectively reviewed to identify cases of cerebral arteriopathy and MGDA, including radiographic and clinical records documenting patient outcomes of medical and surgical management. Thirteen cases of moyamoya syndrome (MMS) associated with MGDA were identified in 13 children aged 0.6-17 years. The pattern of arteriopathy resembled that of non-MGDA MMS, with predominantly anterior circulation involvement. The arteriopathy lateralized with the MGDA, although 3 patients also had contralateral involvement. The overall group was followed for a median of 3.2 years. Radiological biomarkers of cerebral ischemia were applied to guide surgical decisions, and more than half of the patients (7 of 13) had evidence of stroke or progression on serial imaging. Nine patients underwent revascularization surgery, and 4 were managed medically. Cerebral arteriopathy observed in association with MGDA resembles MMS seen in patients without MGDA and is dynamic, with progression observed over months to years and an associated risk of cerebral ischemia that indicates a role for surgical revascularization. Radiological biomarkers may augment clinical data to identify candidates for revascularization surgery.


Unified model and reverse recovery nonlinearities of the driven diode resonator.
We study the origins of period doubling and chaos in the driven series resistor-inductor-varactor diode (RLD) nonlinear resonant circuit. We find that resonators driven at frequencies much higher than the diode reverse recovery rate do not show period doubling. Models of chaos based on the nonlinear capacitance of the varactor diode display a reverse-recovery-like effect, and this effect strongly resembles reverse recovery of real diodes. We find for the first time that in addition to the known dependence of the reverse recovery time on past current maxima, there are also important nonlinear dependencies on pulse frequency, duty cycle, and dc voltage bias. Similar nonlinearities are present in the nonlinear capacitance models of these diodes. We conclude that a history-dependent and nonlinear reverse-recovery time is an essential ingredient for chaotic behavior of this circuit, and demonstrate for the first time that all major competing models have this effect, either explicitly or implicitly. Besides unifying the two major models of RLD chaos, our work reveals that the nonlinearities of the reverse-recovery time must be included for a complete understanding of period doubling and chaos in this circuit.


Health services, health manpower, and universities in relation to health for all: an historical and future perspective.
The World Health Organization's goal of Health for All by the Year 2000 (HFA) has become a major force in national and international health policies. This paper deals with some of the historical roots of HFA and describes ways in which the major components of the health sector--health services, manpower, and universities--have evolved and should evolve in the future if they are to support the idea of HFA. One conclusion is that the changes called for in relation to HFA are not simply incremental extensions of previous values, structures, and functions. Rather a radical break with the past is often required. To expect otherwise is to misunderstand how fundamentally the concepts of HFA differ from values that have governed the health sector in the past. A second conclusion is that recent decades have seen a remarkable progression of new ideas and changes in the health sector, so much so that the changes called for by HFA are not so improbable as one might otherwise think.


Sorafenib induces renal cell carcinoma apoptosis via upregulating activating transcription factor 4.
Previous studies have shown sorafenib to function as a multitargeted tyrosine kinase inhibitor in different tumors. However, whether sorafenib improves renal cell carcinoma (RCC) through activating transcription factor 4 (ATF4) has never been explored. In the current study, we showed that sorafenib could suppress RCC cell viability in a time- and dose-dependent manner. Furthermore, sorafenib is demonstrated to enhance the mRNA and protein levels of ATF4. Meanwhile, overexpression of ATF4 was demonstrated to induce ACHN cell cycle arrest and cell apoptosis. Moreover, treatment with sorafenib could enhance the expression of CCAAT/enhancer-binding protein-homologous protein (CHOP) and p53 upregulated modulator of apoptosis (PUMA), thereby leading to ACHN cell apoptosis. More importantly, silencing of ATF4 could largely abolish sorafenib-induced upregulation of CHOP and PUMA in ACHN cells. Meanwhile, sorafenib-induced cell apoptosis may be dependent on the activation of ATF4 since knockdown of ATF4 partially reversed sorafenib-induced ACHN cell apoptosis. In summary, the present study demonstrates that sorafenib activates ATF4-CHOP-PUMA pathway in RCC cells, resulting in enhanced ER stress-related cell apoptosis.


Optical absorption and photoluminescence studies of gold nanoparticles deposited on porous silicon.
We present an investigation on a coupled system consists of gold nanoparticles and silicon nanocrystals. Gold nanoparticles (AuNPs) embedded into porous silicon (PSi) were prepared using the electrochemical deposition method. Scanning electron microscope images and energy-dispersive X-ray results indicated that the growth of AuNPs on PSi varies with current density. X-ray diffraction analysis showed the presence of cubic gold phases with crystallite sizes around 40 to 58 nm. Size dependence on the plasmon absorption was studied from nanoparticles with various sizes. Comparison with the reference sample, PSi without AuNP deposition, showed a significant blueshift with decreasing AuNP size which was explained in terms of optical coupling between PSi and AuNPs within the pores featuring localized plasmon resonances.


Women's lived experiences of learning to live with osteoporosis: a longitudinal qualitative study.
A vast amount of literature exists concerning pharmaceutical adherence in osteoporosis. However, the process of learning to live with osteoporosis over time remains largely unknown. The purpose of this study was to gain a deeper understanding of the continued process of how women learn to live with osteoporosis. Our objective was to explore what characterizes women's experiences of living with osteoporosis during the first year after diagnosis, when patients are prescribed anti-osteoporotic treatment, without having experienced an osteoporotic fracture. Forty-two narrative qualitative interviews were conducted with fifteen recently diagnosed Danish women. A longitudinal design was chosen since this allows an investigation of the perspective over time. The interviews were conducted in the period of March 2011 to August 2012. Data were analyzed using a phenomenological-hermeneutic interpretation of text. No medical records were available for the researchers. All information with the exception of T-score was self-reported. The participants' experiences could be described in two key themes developed through the analysis: 1) "To become influenced by the medical treatment" which consisted of two sub-themes "taking the medication", and "discontinuing the medication". 2) "Daily life with osteoporosis", which was characterized by three sub-themes: "interpretation of symptoms", "interpretation of the scan results" and "lifestyle reflections". The results highlighted that learning to live with osteoporosis is a multifaceted process that is highly influenced by the medical treatment. In some cases, this is a prolonged process that can take around one year. The results suggest a need for improved support for individual women during the complex process of learning to live with osteoporosis. The study adds new knowledge that can be useful for healthcare professionals taking a health-oriented stance when supporting women in self-management of their illness. Further investigations of lived experiences over time in the field of osteoporosis research are therefore needed.


Effects of aging on the recall of extended expository prose.
Groups of young and old adults read a 5 1/2 page passage of expository prose under one of two instructional treatments. Since previously observed deficits in older adults' memory may be due to the level of processing, one instructional treatment was intended to encourage deeper processing. Vocabulary and a measure of current reading activity were used as covariates. As with previous work, young adults recalled more than old adults and also had more intrusions in their recall protocols. There was no effect for instructional treatment but older adults showed the same sensitivity to the relative importance of information as younger adults.


The Role of Online Social Identity in the Relationship Between Alcohol-Related Content on Social Networking Sites and Adolescent Alcohol Use.
Social networking sites (SNSs) are social platforms that facilitate communication. For adolescents, peers play a crucial role in constructing the self online through displays of group norms on SNSs. The current study investigated the role of online social identity (OSI) in the relationship between adolescent exposure to alcohol-related content posted by peers on SNSs and alcohol use. In a sample (N = 929) of Australian adolescents (Age M = 17.25, SD = 0.31) higher levels of exposure to alcohol-related content on SNSs was associated with higher levels of alcohol use. Importantly, the association was stronger when the participants reported higher OSI particularly when also reporting low or moderate amount of time spent on SNS. The findings can be explained by social identity literature that demonstrates individuals align their behaviors with other members of their social group to demonstrate, enact, and maintain social identity. The results of this study reflect the importance of considering the construction of the "self" through online and offline constructs.


Ventricular free wall rupture: sudden, subacute, slow, sealed and stabilized varieties.
Six cases of acute myocardial infarction with blood in the pericardial sac are described. In one case rapid death followed myocardial rupture leaving no time for the possibility of intervention. Of two other cases acute symptoms developing after myocardial rupture, one was operated on promptly and the other, whose condition improved on pericardiocentesis, after a delay of a few hours. Both are now long term survivors A fourth patient probably had two episodes of rupture which apparently sealed off. He underwent cardiac catheterization, but no epicardial leak was found. Subsequently at operation a sealed myocardial rupture was detected and sutured over. The fifth patient suffered a silent myocardial rupture. A false aneurysm was diagnosed four months later and he withstood successful surgery. In the sixth patient, the course was similar to that of case 1, namely rapid death with a clinical picture suggestive of tamponade. Postmortem examination showed a covert rupture with some evidence of attempts to plug the opening. The purpose of this report is to emphasize the varying course which myocardial rupture can take.


Pore Evolution in Cell Walls of Food Tissue during Microwave-Assisted Drying: An In-Depth Investigation.
Microwave (MW) heating is a unique approach that, unlike conduction- and convection-based heating, can provide volumetric heating. Complex microstructural changes in food materials occur because of simultaneous heat and mass transfer during drying, significantly affecting food structure and quality. Food properties, drying methods, and other drying parameters all have an impact on the microstructure of food samples, which in turn affects drying kinetics and food quality. However, no study has been undertaken to investigate the development of nano-micro-pores (NM-pores) on the cell walls and their relationship with the moisture migration mechanism. This study presents a novel investigation of the microstructural changes in food during microwave drying, with a focus on the formation of nano-micro-pores (NM-pores) on cell walls and their impact on moisture transport kinetics. The utilized hot air was maintained at a temperature of 70 °C, whereas microwave (MW) power levels of 100 W, 200 W, 300 W, and 400 W were used in microwave drying. The findings of the study indicate that the development of NM-pores occurs only during intermittent microwave drying (IMCD), while the cell wall of the food samples tends to burn or collapse in continuous microwave drying (CMD) due to the high heat generated. Additionally, no NM-pores were observed in the cell wall during convective drying. During IMCD with microwave power ranging from 100 W to 400 W, a range of pore sizes from 0.1 μm to 8.5 μm were observed. Due to the formation of NM-pores and collapses, MW drying takes around 10-20 times less time than convective drying to remove the same quantity of moisture. The effective moisture diffusivity values were found to be the highest in CMD at 4.70 × 10-07 m2/s and the lowest in CD at 2.43 × 10-09 m2/s. IMCD showed a moderate diffusivity of 2.45 × 10-08 m2/s. This study investigates the formation of NM-pores on cell walls during microwave drying and their impact on moisture transport kinetics and establishes correlations between microstructure modifications and moisture migration pathways.


Optimization and characterization of biosurfactant production from marine Vibrio sp. strain 3B-2.
A biosurfactant-producing bacterium, designated 3B-2, was isolated from marine sediment and identified as Vibrio sp. by 16S rRNA gene sequencing. The culture medium composition was optimized to increase the capability of 3B-2 for producing biosurfactant. The produced biosurfactant was characterized in terms of protein concentration, surface tension, and oil-displacement efficiency. The optimal medium for biosurfactant production contained: 0.5% lactose, 1.1% yeast extract, 2% sodium chloride, and 0.1% disodium hydrogen phosphate. Under optimal conditions (28°C), the surface tension of crude biosurfactant could be reduced to 41 from 71.5 mN/m (water), while its protein concentration was increased to up to 6.5 g/L and the oil displacement efficiency was improved dramatically at 6.5 cm. Two glycoprotein fractions with the molecular masses of 22 and 40 kDa were purified from the biosurfactant, which held great potential for applications in microbial enhanced oil recovery and bioremediation.


The role of neurotrophins in muscle under physiological and pathological conditions.
This review summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of development, maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors not only modulates survival and function of innervating motoneurons and proprioceptive neurons but also development and differentiation of myoblasts and muscle fibers. Neurotrophins and neurotrophin receptors play a role in the coordination of muscle innervation and functional differentiation of neuromuscular junctions. However, neurotrophin receptors are also expressed in differentiating muscle cells, in particular at early developmental stages in myoblasts before they fuse. In adults with pathological conditions such as human degenerative and inflammatory muscle disorders, variations of neurotrophin expression are found, but the role of neurotrophins under such conditions is still not clear. The goal of this review is to provide a basis for a better understanding and future studies on the role of these factors under such pathological conditions and for treatment of human muscle diseases.


Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice.
High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals.


Density functional theory of charged, hard-sphere fluids.
An approximate electrostatic (ES) excess free energy functional for charged, hard sphere fluids is presented. This functional is designed for systems with large density variations, but may also be applied to systems without such variations. Based on the Rosenfeld method of perturbation about a bulk (homogeneous) reference fluid [Y. Rosenfeld, J. Chem. Phys. 98, 8126 (1993)], the new ES functional replaces the reference fluid densities with a functional of the particle densities, called the RFD functional. The first-order direct correlation function (DCF) in the particle densities is computed using as input the first- and second-order DCFs in [rho(i)(x)], the inhomogeneous densities defined by the RFD functional. Because this formulation imposes no a priori constraints on the form of the RFD functional-it is valid for any choice of [rho(i)(x)]-the RFD functional may be chosen (1) so that the input DCFs (that is, DCFs in [rho(i)(x)]) may be approximated and (2) so the combination of [rho(i)(x)] and input DCFs yields a good estimate of the first-order DCF in the particle densities. In this way, the general problem of finding the excess free energy functional has been replaced by the specific problem of choosing a RFD functional. We present a particular RFD functional that, together with bulk formulations for the input DCFs, accurately reproduces the results of Monte Carlo simulations.


[Early detection of chronic kidney disease: epidemiological data on renal dysfunction].
Estimated glomerular filtration rate (eGFR) and urinary albumin (U-Alb) have been suggested as indicators for the early identification of persons with kidney dysfunction. The Gubbio Study collected data on serum creatinine, UAlb, other laboratory indices, blood pressure, and medical history in a population sample of 4574 adults (2083 men and 2491 women, age range 18- 95 years). The study included analyses on six disorders which are commonly associated with kidney disease (hypertension, cardiovascular disease, anemia, high serum uric acid, high serum phosphorus/low serum calcium, and high serum potassium). Low eGFR (<60 mL/min per 1.73 m2) was found in 6.6% of men and 6.2% of women. Low eGFR prevalence varied largely with age (from <1% at 18-24 years up to > 30% at > or =75 years in both sexes, p<0.001). On the basis of these data, it was estimated that the prevalence of low eGFR in the whole Italian population could be 1.3 million among men (95%CI 1.1/1.5) and 1.5 million among women (95%CI 1.3/1.8). Data available only for age 45-64 indicate that 6.4% of men and 3.0% of women have high U-Alb (> or =20 microg/min) in the presence of non-low eGFR. Low eGFR was associated with at least two disorders potentially due to kidney disease in the majority of persons but was rarely associated with a previous diagnosis of kidney disease (<5% of cases). These data support the use of eGFR for the screening of people with or at risk of developing kidney disease. Awareness of kidney disease is very low in the Italian population.


IgA nephropathy associated with Crohn's disease.
The relationship between IgA nephropathy (IgAN) and Crohn's disease was reported. IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure, and up to 50% of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis. However, specific and effective therapeutic strategies are still lacking. In this review, we discuss the possibility of the mechanism involved in IgAN associated with Crohn's disease based on the findings of basic and clinical studies. Although the etiology of IgAN associated with Crohn's disease is not permanent and various factors are thought to be involved, the stabilization of the disease condition of Crohn's disease is believed to help treat IgAN.


Truncated O-GalNAc glycans impact on fundamental signaling pathways in pancreatic cancer.
Truncated O-GalNAc glycosylation is an important feature of pancreatic ductal adenocarcinomas (PDAC) and expression of truncated O-GalNAc glycans is strongly associated with decreased survival and poor prognosis. It has been proven, that aberrant O-GalNAc glycosylation influence PDAC signaling to promote oncogenic properties, but elucidation of the influence of truncated O-GalNAc glycosylation on different signaling molecules has just been started. We herein elucidated the impact of aberrant O-GalNAc glycosylation on two important PDAC signaling pathways, namely AKT/mTOR and RAS/MAPK. In PDAC cells expressing truncated O-GalNAc glycans, we identified differentially expressed proteins associated with AKT/mTOR and RAS/MAPK pathways using quantitative proteomics. Since AKT, a key-signaling molecule in PDAC, was among the identified proteins, we analyzed AKT and found a strikingly enhanced S473 phosphorylation and identified a previously unknown O-GalNAc-modification. Consecutive analysis of COSMC knockdowns in PDAC revealed strong effects on AKT upstream and downstream effector molecules. Interestingly, truncated O-GalNAc glycans could facilitate an mTORC1 inhibitor resistance using AZD8055. In addition, as AKT/mTOR pathway has extensive cross talks with RAS/MAPK pathway we analyzed the pathways and found it negatively regulated. Finally, we found that the expression of epithelial-mesenchymal-transition markers, key features of aggressive PDACs cells, are enhanced and truncated O-GalNAc glycans enhance pancreatic cancer cell growth in a xenograft mouse model. Our study demonstrates that truncated O-GalNAc glycans have a strong impact on AKT/mTOR and RAS/MAPK signaling pathways, are modulated by EGF or IGF-1 signaling and should be considered for targeted therapy of these pathways in PDAC.


New technique for endobronchial ultrasound-guided transbronchial needle aspiration to improve diagnostic yield.
Although the pooled sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) using a convex scanning ultrasound bronchoscope is equivalent to the gold standard of mediastinoscopy, diagnosis cannot be obtained in a small number of patients with poor cellularity. The method described was investigated with the aim of avoiding puncturing the cartilage and enabling reliable tissue harvesting, as this can be expected to improve diagnostic yield. Outer sheath method (OSM): While pressing the outer sheath (OS) of the puncture needle gently against the bronchial wall, the hyperechoic line appeared on surface of the bronchial wall on EBUS image. Then pulling and pushing the entire bronchoscope, the tip of OS moved to the epithelium above the bronchial cartilage while detecting the best position for puncturing on the EBUS images simultaneously. The bronchoscopist could visualize the cartilage moving longitudinally on EBUS image. The movement of the cartilage was stopped when the tip of the OS was caught in a concavity between 2 rings of cartilage. Group A consisted of 169 patients who underwent EBUS-TBNA before the introduction of OSM, and group B consisted of 169 patients who underwent EBUS-TBNA after the introduction of OSM. These 2 groups were compared with to investigate the usefulness of OSM. Adding this operation enabled a suitable puncture site to be identified, significantly improving diagnostic yield from 92.7% (group A) to 98.2% (group B). This method was regarded as useful for improving diagnostic yield by enabling the selection of a puncture site between rings of cartilage during EBUS-TBNA.


Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer.
The cardiovascular effects of short-term overt hypothyroidism are not well known. We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and the ankle brachial index (ABI) in thyroid cancer patients with short-term overt hypothyroidism due to thyroid hormone withdrawal (THW). Twenty-one patients requiring radioactive iodine (RAI) ablation or scanning and 36 healthy control subjects were enrolled. Patients were evaluated in the subclinical thyrotoxic phase when they were on suppressive levothyroxine therapy and in the overt hypothyroid phase due to THW for four weeks. PCSK9, sLOX-1, lipids and ABI were measured in the patient and control groups. Total cholesterol, LDL cholesterol, triglycerides and Apo B levels were increased in short overt hypothyroidism compared with the control group (p<0.001). PCSK9 levels increased before THW and after THW in the patients compared to control group (p<0.001, p=0.004, respectively). sLOX-1 levels were not different between patients with short term overt hypothyroidism and control group (p=0.27). ABI was found to be significantly decreased in patients with thyroid cancer before and after THW compared to control group (p=0.04, p=0.002 respectively). PCSK9 levels were correlated negatively with ABI (r=-0.38, p=0.004). In conclusion; our study demonstrated that patients with differentiated thyroid cancer both before and after THW which is a short term overt hypothyroid phase, had increased PCSK9 levels and decreased ABI. Short term overt hypothyroidism also leads to increased HDL, LDL, total cholesterol, Apo A and Apo B levels.


Amphiphiles in aqueous solution: well beyond a soap bubble.
Owing to their "dual" affinity, amphiphiles self-assemble in water to form different kinds of nanoscale multimolecular assemblies ranging from simple micelles and vesicles to highly organized fibers, helices and tubes. In this tutorial review the aggregates formed in water by head/tail amphiphiles are revisited and discussed from the point of view of supramolecular chemistry with a focus on their structure and recognition abilities. Their applications in materials chemistry, as soft templates for inorganic nanostructures, as well as in biological and medicinal chemistry are also illustrated. Special attention is paid to highlight intriguing aspects, for example the control of morphology and chirality, their modulation by experimental parameters and chiral symmetry breaking.


Ruminal escape protein for lightweight feedlot calves.
Effects of supplemental ruminal escape protein (REP) were evaluated in an 84-d growth study involving 140 feedlot steers (198 kg) and in a site of digestion study involving four steers (149 kg). Dietary treatments were as follows: 1) basal diet; 2) basal diet plus 2% of a REP blend (1/3 blood meal, 1/3 meat and bone meal, and 1/3 feather meal); 3) basal diet plus 4% REP; and 4) basal diet plus 6% REP. The basal diet contained 18% alfalfa hay, 10% sudangrass hay, 61% steam-flaked corn, 2.5% yellow grease, 6% molasses, and 2.5% supplement. The basal diet contained 12.2% CP, and urea was the sole source of supplemental N. There was a quadratic effect (P < .05) of REP supplementation on rate and efficiency of gain. The greatest response was with 2% REP, which increased rate and efficiency of gain by 13.4 and 8.4%, respectively, over that of the basal diet. Protein supplementation had a quadratic effect (P < .05) on the NE value of the diet. The addition of 2% supplemental REP increased the NE of the diet by 6.6%. In the site of digestion trial, supplemental REP linearly increased (P < .01) passage of nonammonia and amino acid N to the small intestine. Compared with estimated amino acid requirements and with muscle composition, postruminal supplies of arginine, histidine, lysine, methionine, and phenylalanine were the limiting amino acids in the basal diet. Excess bypass protein, by placing an additional demand on arginine for detoxification of ammonia, may limit growth and performance.


Quasispecies evolution of the prototypical genotype 1 porcine reproductive and respiratory syndrome virus early during in vivo infection is rapid and tissue specific.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major infectious threat to the pig industry worldwide. Increasing evidence suggests that microevolution within a quasispecies population can give rise to high sequence heterogeneity in PRRSV; potentially impacting the pathogenicity of the virus. Here, we report on micro-evolutionary events taking place within the viral quasispecies population in lung and lymph node 3 days post infection (dpi) following experimental in vivo infection with the prototypical Lelystad PRRSV (LV). Sequence analysis revealed 16 high frequency single nucleotide variants (SNV) or differences from the reference LV genome which are assumed to be representative of the consensus inoculum genome. Additionally, 49 other low frequency SNVs were also found in the inoculum population. At 3 dpi, a total of 9 and 10 SNVs of varying frequencies could already be detected in the LV population infecting the lung and lymph nodes, respectively. Interestingly, of these, three and four novel SNVs emerged independently in the two respective tissues when compared to the inoculum. The remaining variants, though already present at lower frequencies in the inoculum, were positively selected and their frequency increased within the quasispecies population. Hence, we were able to determine directly from tissues infected with PRRSV the repertoire of genetic variants within the viral quasispecies population. Our data also suggest that microevolution of these variants is rapid and some may be tissue-specific.


The relationships between obsessional personality, obsessions in depression, and symptoms of depression.
The relationships between obsessional personality, obsessions in depression, and symptoms of depression were investigated by means of a retrospective study of case notes and item sheets. One hundred and sixty-eight cases of depression, aged 20 to 29 years, were rated for obsessional personality as defined by Ingram (1961). The presence of previous obsessions, of obsessions in depression and of eight symptoms of depression was assessed from the item sheets. Obsessional personality was found to be significantly associated only with a decreased frequency of objective apathy, although it seemed to act to reduce the anxiety experienced by those with obsessions, in depression. Obsessions in depression were associated with rapid changes of mood, anxiety, agitation and overactivity and with a relative absence of retardation.


Transcranial magnetic stimulation over the posterior cerebellum during smooth pursuit eye movements in man.
Recent neurophysiological experiments in the monkey have demonstrated that the flocculus and the posterior vermis, lobules VIc-VII (oculomotor vermis), are involved in the generation of pursuit eye movements. Whereas the functions of the flocculus in the control of smooth pursuit have been intensively investigated, sufficient data are not available for a profitable discussion of the functions of the oculomotor vermis in the control of smooth pursuit. We previously indicated that the posterior vermis can be electrically stimulated by a focal transcranial magnetic stimulation (TMS) device through the skull in man, and that focal TMS of the posterior vermis can modulate saccadic eye movements. In this study we investigated the effects of cerebellar stimulation on smooth pursuit metrics in man using a focal TMS device. Focal TMS was applied over the posterior cerebellum in an area approximately 7 mm lateral and caudal to the inion, where saccadic eye movements are modulated by TMS, during horizontal smooth pursuit elicited by a step-ramp target with a constant velocity of 15 degrees/s in four normal subjects. The TMS device was triggered after the onset of smooth pursuit during the initial acceleration phase (latency range = 40-80 ms) or the steady-state tracking phase (latency range = 300-340 ms). We investigated the effect of TMS on the velocity and acceleration of smooth pursuit. For smooth pursuit directed ipsilateral to the stimulation side (ipsiversive), focal TMS of the posterior cerebellum produced abrupt acceleration of pursuit in both initial acceleration and steady-state tracking phases. On the other hand, TMS produced abrupt deceleration of contraversive pursuit in both initial acceleration and steady-state tracking phases. These findings suggest that the posterior vermis controls smooth pursuit velocity in a direction-selective manner in both initial acceleration and steady-state tracking phases.


GPR55, a lysophosphatidylinositol receptor with cannabinoid sensitivity?
Emerging data indicates the existence of novel molecular targets for cannabinoid ligands and recently it has been suggested that the orphan G-protein coupled receptor, GPR55 can be activated by a range of endogenous, plant and synthetic cannabinoids. However, to date, the most potent ligand identified for GPR55 is the endogenous phospholipid, lysophosphatidylinositol (LPI). GPR55 is thought to link predominantly G-protein alpha(13), where it promotes Rho-dependent signalling. Additional events downstream of GPR55 include activation of ERK-MAP kinase and Ca(2+) release from stores, as well as the induction of a number of transcription factors. Although GPR55 has only a low sequence identity with the CB1 or CB2 cannabinoid receptors, it clearly interacts with certain cannabinoid ligands. However, the nature and scope of these effects are presently unclear and they may be influenced by the assay and cellular background used for their study. This article reviews the current status of GPR55 pharmacology and its putative endogenous ligand, lysophosphatidylinositol LPI.


Micrografting: An Old Dog Plays New Tricks in Obligate Plant Pathogens.
Micrografting, which was developed almost 50 years ago, has long been used for virus eradication, micropropagation, regeneration, rejuvenation, and graft compatibility. Recently, micrografting has been used for studies of long-distance trafficking and signaling of molecules between scions and rootstocks. The graft transmissiveness of obligate plant pathogens, such as viruses, viroids, and phytoplasmas, facilitated the use of micrografting to study biological indexing and pathogen transmission, pathogen-induced graft incompatibility, and screening for the pathogen resistance during the past 20 years. The present study provides comprehensive information on the latter subjects. Finally, prospects are proposed to direct further studies.


Olfactory responses to aphid and host plant volatile releases: (E)-beta-farnesene an effective kairomone for the predator Adalia bipunctata.
The volatiles released from several aphid and host plant species, alone or associated, were studied for their infochemical role in prey location. Using a four-arm olfactometer, the attraction of several combinations of three aphid (Myzus persicae, Acyrthosiphon pisum, and Brevicoryne brassicae) and three plant (Vicia faba, Brassica napus, and Sinapis alba) species toward Adalia bipunctata larvae and adults was observed. Both predatory larvae and adults were attracted only by A. pisum and M. persicae when they were crushed, whatever the host plant. (E)-beta-farnesene, the aphid alarm pheromone, was the effective kairomone for the ladybird. Plant leaves alone (V. faba, B. napus, and S. alba) or in association with nonstressed whole aphids (the three species) did not have any attraction for the predator. The B. brassicae specialist aphid is the only prey that was not attracted to A. bipunctata larvae and adults, even if they were crushed. Release of B. brassicae molecules similar to the host plant allelochemicals was demonstrated by GC-MS analysis. The lack of behavioral response of the ladybird at short distance toward the cruciferous specialist aphid was related only to the absence of (E)-beta-farnesene in the aphid prey volatile pattern.


[Subchronic toxicity of gamma-Falisan-Universal dry dressing agent to rats].
Doses of 50 mg/kg, 100 mg/kg, and 400 mg/kg of Gamma-Falisan-Universal dry dressing agent (active ingredients including 20 per cent of Lindan and 2.5 per cent of phenyl-mercury acetate) were administered in agar suspension by stomach intubation to rats over 13 weeks, with five applications weekly. The following changes were produced: retardation in body weight, lymphopenia and leucopenia, rise of segment-nuclear neutrophils in peripheral blood, decrease of haematocrit and haemoglobin, as well as rise in activities of leucine aminopeptidase and serum glutamate oxalo-acetate transaminase. The males proved to be more sensitive in the context of their haematological parameters, while the females displayed higher sensitivity in terms of clinico-chemical values. Absolute weight increases were recorded from kidneys and liver of both males and females and from the adrenal gland of females, while weight loss was recorded from the pituitary gland of males. Changes of the same kind were expressed even more strongly, in the context of relative weights of organs. Histopathological changes were recorded from liver, kidneys, and adrenal gland of either sex, and they were histometrically confirmed. Retardation in body weight, rise in activity of leucine aminopeptidase, and weight changes of various organs were significant up to first dosage group. Analogous findings were obtained with regard to microscopic changes in kidneys. Hence, no-effect levels did not occur at all throughout the experiment.


Biomineralization-Inspired Copper Sulfide Decorated Aramid Textiles via In Situ Anchoring toward Versatile Wearable Thermal Management.
Designing smart textiles for personal thermal management (PTM) is an effective strategy for thermoregulation and energy saving. However, the manufacture of versatile high-performance thermal management textiles for complex real-world environments remains a challenge due to the limitations of functional integration, material properties, and preparation procedures. In this study, an aramid fabric based on in situ anchored copper sulfide nanostructure is developed. The textile with excellent solar and Joule heating properties can effectively keep the body warm even at low energy inputs. Meanwhile, the reduced infrared emissivity of the textile decreases the thermal radiation losses and helps to maintain a constant body temperature. Impressively, the textile integrates superb electromagnetic shielding, near-complete UV protection properties, and ideal resistance to fire and bacteria. This work provides a simple strategy for fabricating multi-functional integrated wearable devices with flexibility and breathability, which is highly promising in versatile PTM applications.


Distribution patterns and drivers of urban green space and plant diversity in Haikou, China.
Investigating historical and ongoing changes in urban green space (UGS) and urban plant diversity (UPD) provides critical insights into urban ecology and urban planning development. The present study illuminates some of the transformations which can occur in rapidly developing urban landscapes. In this work, we used 30 m resolution images from the Landsat 5 satellite from 2015 to investigate UGS patterns in Haikou City, China. Metrics of UPD were obtained using field surveys, allowing the proportion of UGS and UPD to be determined in each urban functional unit (UFU) of Haikou. The results revealed that leisure and entertainment areas (such as parks) had the highest diversity, whereas roads and transportation hubs had the lowest. More frequent anthropogenic maintenance had a positive effect on the total number of species, including cultivated, tree, and herb species. Similarly, increased watering frequency had a positive impact on the diversity of cultivated and shrub species. By providing demonstrating a crucial link between UGS and UPD, the results provide valuable information for planning sustainable urban development in Haikou City and other tropical regions. They highlight the important role of UGS in maintaining biodiversity and providing a range of ecosystem services. This research will inform policymakers and urban planners about the need to consider UGS and UPD in urban planning and management process, in order to promote sustainability and conservation of biodiversity.


Cardioprotective effects of acute isovolemic hemodilution in a rat model of transient coronary occlusion.
Following isovolemic hemodilution (AIH), lowering blood viscosity induces acceleration of erythrocyte velocity resulting in improved tissue oxygen delivery. Using a rat model of myocardial infarct, we tested the hypothesis that AIH would attenuate myocardial damage due to transient coronary occlusion. Prospective, randomized, and controlled animal study. Animal research laboratory in a university hospital. Male Sprague-Dawley rats. All rats were subjected to 30 mins of left coronary artery occlusion followed by 48 hrs of reperfusion. Before the ischemic period, the anesthetized rats were randomly allocated to undergo either 15 mins of waiting (controls) or AIH to achieve a hematocrit of 30% (AIH-CO) by stepwise blood withdrawal and isovolemic compensation with 6% hydroxyethylstarch 200-0.5. Hemodynamic variables were comparable in the two groups, except for higher indexes of stroke volume in the AIH-CO group. During coronary occlusion and the reperfusion period, AIH resulted in a lower incidence of fatal ventricular tachyarrhythmia (17% vs. 50% in control group, p < .05) and higher survival at 48 hrs of postreperfusion (83% vs. 42%, p < .05).Preischemic hemodilution significantly attenuated myocardial damage as shown by lower release of cardiac troponin I and reduction in myocardial infarct size as measured by tetrazolin staining. Histologic examination revealed no difference regarding peri-ischemic infiltration with neutrophil granulocytes. Our data provide the first experimental demonstration that preischemic moderate AIH confers cardioprotection and improves survival in a rat model of myocardial infarct.


Treatment with Growth Hormone for Adults with Growth Hormone Deficiency Syndrome: Benefits and Risks.
Pharmacological treatment of growth hormone deficiency (GHD) in adults began in clinical practice more than 20 years ago. Since then, a great volume of experience has been accumulated on its effects on the symptoms and biochemical alterations that characterize this hormonal deficiency. The effects on body composition, muscle mass and strength, exercise capacity, glucose and lipid profile, bone metabolism, and quality of life have been fully demonstrated. The advance of knowledge has also taken place in the biological and molecular aspects of the action of this hormone in patients who have completed longitudinal growth. In recent years, several epidemiological studies have reported interesting information about the long-term effects of GH replacement therapy in regard to the possible induction of neoplasms and the potential development of diabetes. In addition, GH hormone receptor polymorphism could potentially influence GH therapy. Long-acting GH are under development to create a more convenient GH dosing profile, while retaining the excellent safety, efficacy, and tolerability of daily GH. In this article we compile the most recent data of GH replacement therapy in adults, as well as the molecular aspects that may condition a different sensitivity to this treatment.


Blood Pressure Regulation by the Rostral Ventrolateral Medulla in Conscious Rats: Effects of Hypoxia, Hypercapnia, Baroreceptor Denervation, and Anesthesia.
Current understanding of the contribution of C1 neurons to blood pressure (BP) regulation derives predominantly from experiments performed in anesthetized animals or reduced ex vivo preparations. Here, we use ArchaerhodopsinT3.0 (ArchT) loss-of-function optogenetics to explore BP regulation by C1 neurons in intact, unanesthetized rats. Using a lentivirus that expresses ArchT under the Phox2b-activated promoter PRSx8 (PRSx8-ArchT), ∼65% of transduced neurons were C1 (balance retrotrapezoid nucleus, RTN). Other rats received CaMKII-ArchT3.0 AAV2 (CaMKII-ArchT), which transduced C1 neurons and larger numbers of unidentified glutamatergic and GABAergic cells. Under anesthesia, ArchT photoactivation reduced sympathetic nerve activity and BP and silenced/strongly inhibited most (7/12) putative C1 neurons. In unanesthetized PRSx8-ArchT-treated rats breathing room air, bilateral ArchT photoactivation caused a very small BP reduction that was only slightly larger under hypercapnia (6% FiCO2), but was greatly enhanced during hypoxia (10 and 12% FiO2), after sino-aortic denervation, or during isoflurane anesthesia. The degree of hypotension correlated with percentage of ArchT-transduced C1 neurons. ArchT photoactivation produced similar BP changes in CaMKII-ArchT-treated rats. Photoactivation in PRSX8-ArchT rats reduced breathing frequency (FR), whereas FR increased in CaMKII-ArchT rats. We conclude that the BP drop elicited by ArchT activation resulted from C1 neuron inhibition and was unrelated to breathing changes. C1 neurons have low activity under normoxia, but their activation is important to BP stability during hypoxia or anesthesia and contributes greatly to the hypertension caused by baroreceptor deafferentation. Finally, C1 neurons are marginally activated by hypercapnia and the large breathing stimulation caused by this stimulus has very little impact on resting BP.SIGNIFICANCE STATEMENT C1 neurons are glutamatergic/peptidergic/catecholaminergic neurons located in the medulla oblongata, which may operate as a switchboard for differential, behavior-appropriate activation of selected sympathetic efferents. Based largely on experimentation in anesthetized or reduced preparations, a rostrally located subset of C1 neurons may contribute to both BP stabilization and dysregulation (hypertension). Here, we used Archaerhodopsin-based loss-of-function optogenetics to explore the contribution of these neurons to BP in conscious rats. The results suggest that C1 neurons contribute little to resting BP under normoxia or hypercapnia, C1 neuron discharge is restrained continuously by arterial baroreceptors, and C1 neuron activation is critical to stabilize BP under hypoxia or anesthesia. This optogenetic approach could also be useful to explore the role of C1 neurons during specific behaviors or in hypertensive models.


Tissue-engineered bone using mesenchymal stem cells and a biodegradable scaffold.
Bone marrow has been shown to contain a population of rare cells capable of differentiating to the cells that form various tissues. These cells, referred to as mesenchymal stem cells (MSCs), are capable of forming bone when implanted ectopically in an appropriate scaffold. The aim of this study was to investigate the potential of a new beta-tricalcium phosphate (beta-TCP) as a scaffold and to compare the osteogenic potential between beta-TCP and hydroxyapatite (HA). The beta-TCP and HA loaded with MSCs were implanted in subcutaneous sites and harvested at 1, 2, 4, and 8 weeks after implantation for biochemical and histological analysis. Biochemically, in both beta-TCP and HA composites, the alkaline phosphatase activity in the composites could be detected and was maintained at a high level for 8 weeks. In the histological analysis, active bone formation could be found in both the beta-TCP and HA composites. These findings suggest that beta-TCP could play a role as a scaffold as well as HA. The fabricated synthetic bone using biodegradable beta-TCP as a scaffold in vivo is useful for reconstructing bone, because the scaffold material is absorbed several months after implantation.


Using a site-specific technical error to establish training responsiveness: a preliminary explorative study.
Even though cardiorespiratory fitness (CRF) training elicits numerous health benefits, not all individuals have positive training responses following a structured CRF intervention. It has been suggested that the technical error (TE), a combination of biological variability and measurement error, should be used to establish specific training responsiveness criteria to gain further insight on the effectiveness of the training program. To date, most training interventions use an absolute change or a TE from previous findings, which do not take into consideration the training site and equipment used to establish training outcomes or the specific cohort being evaluated. The purpose of this investigation was to retrospectively analyze training responsiveness of two CRF training interventions using two common criteria and a site-specific TE. Sixteen men and women completed two maximal graded exercise tests and verification bouts to identify maximal oxygen consumption (VO2max) and establish a site-specific TE. The TE was then used to retrospectively analyze training responsiveness in comparison to commonly used criteria: percent change of >0% and >+5.6% in VO2max. The TE was found to be 7.7% for relative VO2 max. χ2 testing showed significant differences in all training criteria for each intervention and pooled data from both interventions, except between %Δ >0 and %Δ >+7.7% in one of the investigations. Training nonresponsiveness ranged from 11.5% to 34.6%. Findings from the present study support the utility of site-specific TE criterion to quantify training responsiveness. A similar methodology of establishing a site-specific and even cohort specific TE should be considered to establish when true cardiorespiratory training adaptations occur.


[Effects of cephem antibiotics on ethanol metabolism].
Disulfiram-like reactions have been reported in patients receiving cephem antibiotics which possess a mercaptomethyltetrazole (Me-TZ) side chain in their molecular structure. The present study focused on the elucidation of the relationship between the formation of Me-TZ and its inhibitory action on alcohol metabolism after treatment with the cephem antibiotics. The cumulative urinary excretion of Me-TZ was determined in healthy volunteers and laboratory animals after i.v. administration of the cephem antibiotics: cefmetazole (CMZ), cefoperazone (CPZ) and latamoxef (LMOX). In humans, monkeys and rodents, the extent of urinary excretion of Me-TZ was found in the order of CPZ greater than LMOX greater than CMZ-treatment. To assess their influences on dehydrogenation of ethanol (EtOH) and acetaldehyde (AcH), rats and monkeys were treated with a single or multiple i.v. dose of Me-TZ and cephem antibiotics prior to the EtOH treatment. The blood EtOH levels were not affected with either the Me-TZ or the cephem pretreatments. On the contrary, the AcH levels were significantly elevated with each of the pretreatments. The dose response curves for AcH levels showed parallel lines corresponding to the urinary excretion of Me-TZ, i.e., CPZ greater than LMOX greater than CMZ-treatment. These results suggest that there are some differences in the disulfiram-like reactions among animal species and antibiotics, which will be attributed to the intrinsic distribution and stability of each of the antibiotics in the body.


Long-term stability following surgical orthodontic treatment of mandibular prognathisms: investigation by means of lateral X-ray cephalogram.
The purpose of this study was to investigate the long-term stability of jaw relations and occlusion following surgical orthodontic treatment of mandibular prognathisms and skeletal openbites. Subjects consisted of fifteen adult patients. Ten patients underwent the sagittal split ramus osteotomy (SSRO) of the mandible and five patients underwent two jaw surgery (Le Fort I osteotomy of the maxilla and SSRO of the mandible). They were observed over five years after the end of active treatment, and lateral X-ray cephalograms were taken at each stage. In the SSRO group, pogonion was retrograded an average of 8.7mm due to the operation and it was further replaced 0.4mm backward after the end of active treatment. Although the vertical distance between nasion and menton decreased 2.9mm between the operative period, it increased 1.8mm after the end of active treatment. On the other hand, in the two jaw surgery group, point A was advanced 4.0mm forward and < SNA increased 3.1 degrees between the operative period. Pogonion was retrograded 11.4mm between the same period, but moved 0.7mm forward after the end of active treatment. A comparison of the osteosynthesis methods revealed that pogonion in the wiring group was retrograded 8.3mm backward between the operative period, but moved 2.1mm forward during the postsurgical orthodontic treatment. Pogonion in the rigid group was retrograded 12.6mm backward between the operative period, but moved 1.6mm forward during the postsurgical orthodontic treatment. However, both groups were stabilized completely after the end of active treatment. A comparison of the differences in the orthodontic treatment method revealed that < Ul-SN in the extraction group inclined 8.3 degrees lingually during presurgical orthodontic treatment, but it tipped 7.0 degrees labially during the postsurgical orthodontic treatment and inclined 3.4 degrees lingually after the end of active treatment. < Ul-SN in the non-extraction group inclined 5.5 degrees lingually during the presurgical orthodontic treatment, but it tipped 2.0 degrees labially during the postsurgical orthodontic treatment and inclined 1.9 degrees lingually after the end of active treatment.


Towards a Data-Driven Estimation of Resilience in Networked Dynamical Systems: Designing a Versatile Testbed.
Estimating resilience of adaptive, networked dynamical systems remains a challenge. Resilience refers to a system's capacity "to absorb exogenous and/or endogenous disturbances and to reorganize while undergoing change so as to still retain essentially the same functioning, structure, and feedbacks." The majority of approaches to estimate resilience requires exact knowledge of the underlying equations of motion; the few data-driven approaches so far either lack appropriate strategies to verify their suitability or remain subject of considerable debate. We develop a testbed that allows one to modify resilience of a multistable networked dynamical system in a controlled manner. The testbed also enables generation of multivariate time series of system observables to evaluate the suitability of data-driven estimators of resilience. We report first findings for such an estimator.


A Determination of the Caffeine Content in Dietary Supplements According to Green Chemistry Principles.
Caffeine is a natural psychoactive substance that belongs to a group of chemical compounds called purine alkaloids. Caffeine is found in various plants such as coffee, tea, cocoa, guarana, and yerba mate. It is often added to dietary supplements for its ability to increase metabolism and aid in weight loss. To determine the caffeine content in dietary supplements, a novel UHPLC method was developed, compatible with the rules of green analytical chemistry. The developed method used only water and ethanol for sample preparation and chromatographic separation on a short C18 column. The obtained method confirmed that caffeine may be analyzed using only environmentally friendly solvents, ethanol, and water. The developed method is characterized by its low limit of quantitation, equal to 0.047 µg/mL, and good reproducibility (a relative standard deviation lower than 1.1%). The obtained results show that the caffeine content in tested dietary supplements is 4-35% higher than the declared amount in most cases. In comparison, the caffeine content of the drug determined using this method was performed with an accuracy of 0.4% RSD.


Hidradenitis suppurativa associated with systemic lupus erythematosus: A case report.
Hidradenitis suppurativa (HS) is a chronic inflammatory condition characterized by recurrent swollen, deep, and painful abscesses. Several autoimmune conditions have been shown to be associated with HS including inflammatory bowel disease and spondyloarthropathies. 40-year-old female with systemic lupus erythematous (SLE) presented with recurrent abscesses and nodules on her extremities. Early considerations related the described dermatologic findings to the dermatologic manifestations of SLE, however findings from lesion biopsy were suggestive of HS. Prednisone and antibiotic therapy with clindamycin were started. Subsequently upon discharge, the patient was also treated with rifampicin and azathioprine. In this communication, we demonstrate a case of HS in a patient with SLE that significantly improved under antibiotic and immunosuppressant therapy. HS can coexist in patients with SLE. Evidence pertinent to the etiology of HS and its association with other autoimmune conditions implies a possible denominator in the disease etiopathogenesis. Increased awareness of the co-occurrence of the two conditions calls for increased efforts to devise better treatment modalities.


Relevance of complement immunity with brain fog in patients with long COVID.
This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50). This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors. Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33-5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04-2.66). High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.


Pharmacology of the human saphenous vein.
Nowadays, the great saphenous vein is the vascular conduit that is most frequently employed in coronary and peripheral revascularization surgery. It is known that saphenous vein bypass grafts have shorter patency than arterial ones, partly because the wall of the normal saphenous vein has different structural and functional characteristics. The features of this vein can be affected by the large distention pressures it is submitted to during its preparation and insertion into the arterial system. Indeed, a vein graft is subjected to considerable changes in hemodynamic forces upon implantation into the arterial circulation, since it is transplanted from a non-pulsatile, low-pressure, low-flow environment with minimal shear stress to a highpressure system with pulsatile flow, where it undergoes cyclic strain and elevated shear. These changes can be responsible for functional and morphological alterations in the vessel wall, culminating in intima hyperproliferation and atherosclerotic degeneration, which contribute to early graft thrombosis. This review has followed a predetermined strategy for updating information on the human saphenous vein (HSV). Besides presenting the aspects relative to the basic pharmacology, this text also includes surgical aspects concerning HSV harvesting, the possible effects of the major groups of cardiovascular drugs on the HSV, and finally the interference of major cardiovascular diseases in the vascular reactivity of the HSV.


Evaporative Crystallization of Spirals.
Spiral motifs are pervasive in nature, art, and technology due to their functional property of providing compact length. Nature is particularly adept at spiral patterning, and yet, the spirals observed in seashells, hurricanes, rams' horns, flower petals, etc. all evolve via disparate physical mechanisms. Here, we present a mechanism for the self-guided formation of spirals from evaporating saline drops via a coupling of crystallization and contact line dynamics. These patterns are in contrast to commonly observed patterns from evaporation of colloidal drops, which are discrete (rings, concentric rings) or continuous (clumps, uniform deposits) depending on the particle shape, contact line dynamics, and evaporation rate. Unlike the typical process of drop evaporation where the contact line moves radially inward, here, a thin film pinned by a ring of crystals ruptures radially outward. This motion is accompanied by a nonuniform pinning of the contact line due to crystallization, which generates a continuous propagation of pinning and depinning events to form a spiral. By comparing the relevant timescales of evaporation and diffusion, we show that a single dimensionless number can predict the occurrence of these patterns. These insights on self-guided crystallization of spirals could be used to create compact length templates.


Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways.
The phosphatidylinositol 3-kinase (PI3K)/Akt and mTORC1 pathways are frequently activated, representing potential therapeutic targets in acute myeloid leukemia (AML). In 19 AML samples with constitutive PI3K/Akt activation, the rapamycin derivative inhibitor everolimus (RAD001) increased Akt phosphorylation. This mTOR C1-mediated Akt up-regulation was explained by an insulin-like growth factor-1 (IGF-1)/IGF-1 receptor autocrine loop: (1) blast cells expressed functional IGF-1 receptors, and IGF-1-induced Akt activation was increased by RAD001, (2) a neutralizing anti-IGF-1R alpha-IR3 monoclonal antibody reversed the RAD001-induced Akt phosphorylation, and (3) autocrine production of IGF-1 was detected in purified blast cells by quantitative reverse transcription-polymerase chain reaction and immunofluorescence. This RAD001-induced PI3K/Akt up-regulation was due to an up-regulated expression of the IRS2 adaptor. Finally, we observed that concomitant inhibition of mTORC1 and PI3K/Akt by RAD001 and IC87114 induced additive antiproliferative effects. Our results suggest that dual inhibition of the mTORC1 complex and the IGF-1/IGF-1R/PI3K/Akt pathway in AML may enhance the efficacy of mTOR inhibitors in treatment of this disease.


Quenching accumulation of toxic galactose-1-phosphate as a system to select disruption of protein-protein interactions in vivo.
The reverse two-hybrid system has been developed to readily identify molecules or mutations that can disrupt protein-protein interactions in vivo. This system is generally based on the interaction-dependent activation of a reporter gene, whose product inhibits the growth of the engineered yeast cell. Thus, disruption of the interaction between the hybrid proteins can be positively selected because, by reducing the expression of the negative marker gene, it allows cell growth. Although several counter-selectable marker genes are currently available, their application in the reverse two-hybrid system is generally confronted with technical and practical problems such as low selectivity and relatively complex experimental procedures. Thus, the characterization of more reliable and simple counter-selection assays for the reverse two-hybrid system continues to be of interest. We have developed a novel counter-selection assay based on the toxicity of intracellular galactose-1-phosphate, which accumulates upon expression of a galactokinase-encoding GAL1 reporter gene in the absence of transferase activity. Decreased GAL1 gene expression upon dissociation of interacting proteins causes reduction of intracellular galactose-1-phosphate concentrations, thus allowing cell growth under selective conditions.


Quantum effects in ice Ih.
Quantum and classical simulations are carried out on ice Ih over a range of temperatures utilizing the TIP4P water model. The rigid-body centroid molecular dynamics method employed allows for the investigation of equilibrium and dynamical properties of the quantum system. The impact of quantization on the local structure, as measured by the radial and spatial distribution functions, as well as the energy is presented. The effects of quantization on the lattice vibrations, associated with the molecular translations and librations, are also reported. Comparison of quantum and classical simulation results indicates that shifts in the average potential energy are equivalent to rising the temperature about 80 K and are therefore non-negligible. The energy shifts due to quantization and the quantum mechanical uncertainties observed in ice are smaller than the values previously reported for liquid water. Additionally, we carry out a comparative study of melting in our classical and quantum simulations and show that there are significant differences between classical and quantum ice.


[Adolescent males and sex life: Heterogeneous motivations related to sexual debut].
This article describes male adolescents' affective history and reasons for initiating or postponing sexual activity, using interviews with 184 males ages 15 to 19 and residing in the city of São Paulo, Brazil, in 2002. Factors for sexual debut included physical attraction, curiosity, and the desire to lose their virginity, suggesting a profile similar to the male social role. Most of the virgin adolescent males justified their choice based on issues of a romantic order, such as not having found the right person or because they preferred to remain virgin until marrying. The results showed a dual social pattern, valuing the feeling of love and deliverance to the loved one, simultaneously with the pressing physical and instinctive desire for sex. Traditional patterns of masculinity, like the dissociation between sex and love, appear to be transposed to sexual debut, revealing a diversity in the ways of experiencing sexuality during adolescence, related in turn to the sexual and reproductive health of men and their partners.


Effect of inhibitors of choline acetylation on acetylcholine output and motility in response to anticholinesterases and to distension of the lumen of isolated guinea-pig ileum.
Some pharmacological effects of acyl-aryl compounds, which inhibit the enzymatic acetylation of choline, have been studied on the isolated guinea-pig ileum. Diphenylylbutylacetic acid (M.G. 1763) greatly reduced the output of acetylcholine from intestine. The intestinal contractions produced by anticholinesterase drugs were inhibited, while the response to acetylcholine itself was little affected. The contraction of longitudinal muscle elicited by raising intra-luminal pressure was also decreased, while the emptying phase of the peristaltic reflex was scarcely affected. There was a correlation between inhibitory activity and chemical structure.


Role of cytokeratin intermediate filaments in transhepatic transport and canalicular secretion.
The role of cytokeratin filaments in the function of hepatocytes was investigated using a nickel-treated hepatocyte in vitro model. Cytokeratin intermediate filaments were selectively dissociated from the cell cortex by nickel treatment. Cytokeratins and ubiquitin were observed using immunofluorescence and immunoelectron microscopy. Hepatocytic function was assessed by visualizing uptake, transhepatic transport and secretion of fluorescein diacetate and horseradish peroxidase into the bile canaliculi. In control primary cultures, most of the bile canaliculi were surrounded by an inner layer of actin filaments and an outer pericanalicular sheath of cytokeratin filaments and microtubules. The cytoplasmic distribution of ubiquitin was diffuse and particulate. After treatment with NiCl2 (150 micrograms/ml) for 24 hr, the cytokeratin filaments and desmoplakin became focally detached from the cell cortex and retracted to form an aggregate around the nucleus. These aggregates were associated with intense ubiquitin immunoreactivity. Only a few attachments of the cytokeratin filaments to the cell cortex remained. F-actin remained attached to the cell cortex in the areas where the cytokeratin filaments had become detached. The pericanalicular sheath of cytokeratin filaments and the bile canaliculi disappeared and actin was dispersed over the entire cell periphery. Fluorescein diacetate secretion and horseradish peroxidase uptake were almost completely absent in the hepatocytes treated with nickel. The effects of nickel persisted 24 hr after its removal from the medium. It is concluded that cytokeratin intermediate filaments play a critical role in the formation of the bile canaliculus, secretion of fluorescein diacetate and uptake of horseradish peroxidase. Further, our study indicates that cytokeratin ubiquitination occurs during collapse and aggregation of the cytokeratin filaments. The formation of cytokeratin-ubiquitin conjugates during aggregation suggests a role of ubiquitin in the control of cytokeratin organization in hepatocytes in the response to cell stress.


Pharmaceutical entanglements: an analysis of the multiple determinants of ADHD medication effects in a Chilean school.
This article draws upon findings from ethnographic fieldwork conducted in a Chilean school to explore how the effects of globally circulating ADHD medications emerge within the localized contexts of everyday users. An analysis of observations of children on ADHD medications within classroom settings is developed which challenges the assumption, pervasive within biomedical paradigms, that the effects of such medications can be understood as resulting directly from their chemical properties and biological modes of action. Our case study highlights the significance of multiple, interacting determinants of drug effects in an everyday setting, focusing in particular on classroom dynamics, teacher-student relations, and the agency of children taking the medications. We conclude that while ADHD medications may act in part by altering physiological processes, an adequate account of their effects requires that analytic attention extends to the sociomaterial contexts in which medications and users are embedded.


Fluctuations in subsets of splenocytes and isotypes of Ig in young adult and aged mice resulting from Trypanosoma musculi infections.
A prominent feature of parasitic infections is the marked hyperplasia of lymphoid tissues. The resultant disruption of those tissues may be a major cause of the immunodepression that typifies parasitic infections. Trypanosoma musculi infections in mice evoke lymphoid hyperplasia and depressed immune responses. T. musculi infections are more severe in C3H than in C57BL/6 (B6) mice; and more severe in aged mice of either strain, compared with young adults. This report concerns a flow cytometric analysis of splenic leukocytes, identified by various surface Ag, in young and aged, trypanosome-infected mice of C3H and B6 strains. Companion studies included quantification of serum Ig isotypes at intervals during infection. The results support the following conclusions: a) all major types of splenic leukocytes were activated by trypanosome infection resulting in enlargement of the cells and proliferation ("blastogenic response"); b) in all young-adult mice and in aged B6 mice (but not aged C3H mice) Thy-1+, Ly-1+, and Ly-4+ cells increased moderately during infection whereas the number of Ly-2+ cells remained constant; c) all cells of the B lineage increased during the course of infection (except in aged C3H mice) with disproportionate increases in the most mature stage (IgG+); d) the responses of young adult C3H and B6 mice to infection differed as illustrated by the ability of B6, but not C3H, mice to limit hyperplasia and reverse the effect; e) aging of B6 mice was reflected by relative inability to regulate generation of mature Ig-producing cells; f) aging of C3H mice was severe as reflected by the relative inability of most subsets of leukocytes to react to the infection, possibly because of abnormalities that were intrinsic in aged, normal C3H mice. It is likely that: a) disruption of lymphoid tissue, probably mediated by alterations in the production of and responsiveness to cytokines, is responsible for the depressed ability of the immune system to defend against parasites; and b) such disruptive effects, being more pronounced in aged animals and less easily brought under control, account for the greater vulnerability of aged animals to parasitic infection.


Is personalised prehabilitation feasible to implement for patients undergoing oncological treatment for lung cancer at a London teaching hospital? Protocol of a feasibility trial.
There is significant potential to improve outcomes for patients with lung cancer in terms of quality of life and survival. There is some evidence that prehabilitation can help, but, to date, this has only been tested in surgical populations, despite 70%-80% of patients with lung cancer in the UK receiving non-surgical treatment. The physiological and psychological benefits of prehabilitation seen in surgical patients could be extrapolated to those receiving non-surgical treatment, particularly in such a poor prognosis group. With patients and healthcare professionals, we have co-designed a personalised and evidence-based prehabilitation programme. This draws on a conceptual framework that aligns with patient values and needs as well as functional goals. We aim to investigate whether this programme is feasible to implement and evaluate in clinical practice. An open-label, single-group feasibility study incorporating quantitative assessments, a qualitative free text questionnaire and reflective field notes. Thirty participants will be recruited over an eight-month period from a single London teaching hospital. All recruited participants will receive a personalised prehabilitation programme during their oncological treatment. This includes a one-hour face-to-face appointment prior to, at week three and at week six of their treatment regimen as well as a weekly telephone call. Interventions including nutrition, physical activity and psychological well-being are stratified according to a patient's priorities, level of readiness and expressed needs. The primary outcome will be feasibility of the personalised prehabilitation programme in clinical practice by investigating areas of uncertainty regarding patient recruitment, attrition, treatment fidelity, intervention adherence and acceptability of study outcome measures. Secondary outcomes will include quality of life, functional capacity and grip strength. Ethical approval has been obtained from the Health Research Authority (reference number 22/PR/0390). Results of this study will be disseminated through publication in peer-reviewed articles, presentations at scientific conferences and in collaboration with patient and public involvement representatives. NCT05318807.


HMGB1 facilitates hypoxia-induced vWF upregulation through TLR2-MYD88-SP1 pathway.
Increased plasma level of von Willebrand Factor (vWF) is associated with major cardiovascular diseases. We previously reported that multimeric vWF binds to NO synthase and inhibits insulin-induced production of NO, thus promoting insulin resistance during acute hypoxia (AH). However, the transcriptional regulation of vWF during AH is not clearly understood. Here, we investigated the mechanisms underlying the upregulation of vwf in mice. AH significantly upregulates the tlr2, tlr3, myd88, and vwf expression and phosphorylation of specificity protein 1 (SP1). Furthermore, AH significantly upregulates high mobility group box-1 (HMGB1) in a time-dependent manner. Moreover, a TLR2 agonist upregulates vWF but a TLR3 agonist does not. Pretreatment with an HMGB1 inhibitor, TLR2-immunoneutralizing antibody, or SP1 inhibitor significantly inhibits vWF expression. Furthermore, Tlr2 silencing completely inhibited MYD88, vWF expression, and SP1 phosphorylation. However, pretreatment with glycyrrhizic acid or silencing of Tlr2 completely blocks binding of Sp1 to the Vwf promoter, thus inhibiting its expression, and enhances insulin resistance during AH. Patients with type 2 diabetes mellitus also showed significantly elevated levels of HMGB1, TLR2, SP1, and vWF, thereby supporting the results of the murine model of AH. Taken together, HMGB1 upregulates vWF in vivo through the TLR2-MYD88-SP1 pathway in mice.


The inhibitory effect of eupatilin on the agonist-induced regulation of vascular contractility.
The present study was undertaken to investigate the influence of eupatilin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Eupatilin more significantly relaxed fluoride-induced vascular contraction than thromboxane A(2) or phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, eupatilin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of eupatilin on agonist-induced vascular contraction regardless of endothelial function.


Phorbol ester-induced stimulation and phosphorylation of adenylyl cyclase 2.
Adenylyl cyclase 2 was expressed in Sf9 cells by recombinant baculovirus infection. Phorbol 12-myristate 13-acetate (PMA) treatment of cells expressing adenylyl cyclase 2 (AC2) increased basal activity. This increase was blocked by staurosporine, a protein kinase C inhibitor. PMA treatment increased Vmax without affecting Km. Greatest increase in basal activity was seen at physiologically relevant Mg2+ concentrations. PMA treatment did not alter sensitivity to guanine nucleotide stimulatory factor (Gs) but enhanced stimulation at all concentrations of activated Gs alpha subunit tested. AC2 was tagged at the N terminus with an 8-amino acid epitope. Epitope-tagged AC2 was purified to apparent homogeneity in a single step by using an antiepitope antibody-affinity column. The eluate was resolved by SDS/PAGE. Silver staining of the gel showed a 106-kDa band. The purified protein was recognized by antipeptide antibody against a region common to all mammalian adenylyl cyclases. The epitope-tagged enzyme expressed in Sf9 cells was also stimulated by PMA. When cells were labeled with 32P and treated with PMA, a 3-fold increase in 32P incorporation of purified epitope-tagged AC2 was observed. We conclude that activation of protein kinase C results in phosphorylation and stimulation of AC2, a cell-surface G protein effector enzyme. Thus, covalent modification of cell-surface effectors may provide an independent mode for signal transmission through G protein pathways.


Extremely low frequency 7 Hz 100 microT electromagnetic radiation promotes differentiation in the human epithelial cell line HaCaT.
Electromagnetic therapy is a treatment method in which an electromagnetic or magnetic stimulus is used to achieve physiological changes in the body. The specific aim of the present work concerns the effectiveness of low frequency electromagnetic fields to modify the biochemical properties of human keratinocytes (HaCaT). Cells exposed to a 7 Hz 100 microT electromagnetic field for one hour (twice daily), indicated modification in shape and morphology. These modifications were also associated with different actin distribution as revealed by phalloidin fluorescence analysis. Indirect immunofluorescence with fluorescent antibodies against involucrin and beta-Catenin, both differentiation and adhesion markers, revealed an increase in involucrin and beta-Catenin expression, supporting the conclusion that exposure to electromagnetic field carries keratinocytes to an upper differentiation level. This study confirms our previous observation and supports the hypothesis that 7 Hz electromagnetic field, may modify cell biochemistry interfering in the differentiation and cellular adhesion of normal keratinocytes.


Norovirus infection in primary immune deficiency.
Norovirus is acknowledged to be a leading cause of acute gastroenteritis worldwide, and its importance as a cause of chronic infection in immune deficient hosts is increasingly recognised. Current evidence suggests that a coordinated response of innate immune mechanisms, CD8+ cytotoxicity and a humoral response, with CD4+ orchestration, is necessary for norovirus clearance. We explain how primary immune deficiency impairs these host defences and predisposes to chronic infection, associated with protracted diarrhoea, weight loss, and requirement for parenteral nutrition. The mucosal villous atrophy frequently seen in norovirus infection appears to be immune mediated, suggesting that some functional immune response is required in order for chronic norovirus infection to become symptomatic in primary immune deficiency. We provide a comprehensive summary of published cases of norovirus infection in patients with primary immune deficiency. Spontaneous viral clearance has been described; however, the majority of reported cases have had prolonged and severe illness. Treatment strategies are discussed in detail. Approaches that have been tried in patients with primary immune deficiency include exclusion diets, enteral and intravenous immunoglobulins, breast milk, immunosuppressants, ribavirin, and nitazoxanide. To date, only ribavirin has been used with apparent success to achieve clearance of chronic norovirus in primary immune deficiency, and randomised controlled trials are needed to evaluate a number of promising therapies that are discussed.


Sensory characteristics and consumer preference for meat from guinea fowl fed hevea seed meal or cashew nut meal supplemented diets.
This study is part of a series of studies on the possibility of substituting alternative protein source supplements to the diet of guinea fowl in order to improve food security in the fight against poverty on the African Continent. This study assesses the identified sensory characteristics of guinea fowl meat and consumer preferences to determine if the possible alternative supplements identified result in a product acceptable to consumers and if consumer preference was evident. Indigenous guinea fowl or selected breed (Galor animals) were fed a control diet C, a commercial diet I (diet used for guinea fowl in Côte d'Ivoire), or one of 2 experimental diets N (diet C supplemented with 15% cashew nut meal) or diet H (diet C supplemented with 15% detoxified hevea seed meal). Meat samples were assessed by 120-trained people using 18 sensory attributes. Principal component analysis (PCA) showed that meats from guinea fowl fed diet C or diet I were clearly distinguished from guinea fowl fed N or H diets and that meat of indigenous guinea fowl or Galor animals were also clearly distinguished. The results of the hierarchical group analysis showed that meat from guinea fowl fed diet H was the preferred guinea fowl meat. A first partial least squares regression PLSR1 identified the relationships between guinea fowl meat samples, their sensory attributes and consumer preference and showed that 82.6% of the sensory data of the first 2 principal components accounted for 95.5% of the preference. The PLSR2 identified the relationships between guinea fowl samples, their sensory attributes, and their biochemical characteristics and showed that the fat content of the meat determined the intensity of flavor, odor, juiciness, and tenderness of the meat. Our results showed that meat from birds fed diet H was preferred, and thus emphasized the existence of a place for the use of hevea seed meal in guinea fowl diet in Côte d'Ivoire.


Photoletter to the editor: Linear atrophoderma of Moulin progressing slowly over 46 years.
Linear atrophoderma of Moulin is a rare acquired disorder arising most commonly during childhood or adolescence, occurring equally in both sexes and characterized by hyperpigmented atrophoderma in a unilateral bandlike distribution along the lines of Blaschko. Since Moulin et al described the condition in 1992, only a few dozen cases have been reported. It has been postulated that linear atrophoderma of Moulin may be due to mosaicism.A 66-year-old man pre-sen-ted with a 46-year his-to-ry of evol-ving tan soft atro-phic con-fluent plaques in a striking-ly Blasch-koid dis-tri-bu-tion, in-vol-ving the left up-per back, shoulder, up-per arm, chest and flank. Ini-tial on-set, at age 20, con-sis-ted of a single mildly pru-ritic pink patch on the left back that was un-res-pon-sive to topical anti-fun-gals. Each new le-sion arose simi-larly as a pink pru-ritic patch, sub-se-quent-ly be-co-ming de-pressed, hy-per-pig-men-ted, and asym-pto-ma-tic over se-ve-ral years. Le-sions were never scaly, firm, or indu-rated. Punch biopsy speci-mens were obtained. The clinical and histo-patho-lo-gi-cal features con-firmed the diagnosis of linear atrophoderma of moulin.Our present case has the characteristic clinical and histopathological features of linear atrophoderma of Moulin, but is the first reported case with mild pruritus at the onset of each new lesion and progressing slowly over 46 years. The lack of any systemic symptoms or other complications in our patient reaffirms the benign nature of this skin disease.


Acetylcholine activates nonselective cation channels in guinea pig ileum through a G protein.
Acetylcholine (ACh) depolarizes the membrane of mammalian intestinal myocytes by activating a nonselective cation channel (G. D. Benham, T. B. Bolton, and R. J. Lang. Nature Lond. 316: 345-347, 1985; R. Inoue, K. Kitamura, and H. Kuriyama. Pfluegers Arch. 410: 69-74, 1987). Here, we present evidence that occupation of the muscarinic receptor by ACh couples to channel activation via a G protein; the coupling can be blocked by pertussis toxin or by intracellular guanosine 5'-O-(2-thio-diphosphate) (GDP beta S), whereas intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) activates the channel in the absence of ACh. The currents, activated by either ACh or GTP gamma S, are nonadditive, conduct sodium ions, and are similar in their voltage dependence and facilitation by submicromolar calcium ions in the cytosol.


Discovery of Anti-NRLP3 Inflammasome, Immunomodulatory Phytochemicals from the Extract of Habenaria intermediaD. Don: An Unexplored Plant Species.
The present study describes the isolation, identification, and quantification of biomarker compounds in plant extracts of Habenaria intermedia D. Don (Orchidaceae). The isolation of the compounds was carried out from H. intermedia D. Don by repeated column chromatography of petroleum ether and ethanol fractions of extract of tubers. These compounds were characterized by 1H and 13C NMR and mass spectral data. A new quantitative method was established by using high-performance liquid chromatography (HPLC)-PDA. As a result, seven compounds were isolated and characterized. This is the first report of isolation of these compounds from this plant species H. intermedia D.Don. Out of seven isolated compounds, five were used for the quantitative study. A reliable and suitable HPLC method was developed for the well-resolved chromatogram of compounds. The proposed method was applied successfully to the detection and quantification of compounds. This study also represents the immunomodulatory and anti-inflammasome biological studies of isolated natural products. Loroglossol (HBR-4) has been reported to possess immunomodulatory activity. The immunostimulating assay indicated that HBR-4 could significantly promote the cell proliferation, especially via IL-2, TNF-α, and IFN-γ secretion from spleen cells. These results suggested the potential utilization of HBR-4 as an attractive functional health supplement candidate for hypoimmunity population. Additionally, cyclophosphamide-induced immunosuppression was counteracted by treatment with HBR-4, revealing significant increase in hemagglutinating antibody responses and hemolytic antibody responses. The current work revealed the potential anti-inflammasome and immunomodulatory activities of H. intermedia D. Don compounds and validates the usage of this prominent Rasayna plant.