A longitudinal study of plasma insulin and glucagon in women with previous gestational diabetes.
To investigate whether plasma insulin or glucagon predicts later development of diabetes in women with gestational diabetes mellitus (GDM). The subjects studied were 91 women with diet-treated GDM and 33 healthy women. Plasma insulin and glucagon during a 50-g oral glucose tolerance test (OGTT) were measured during pregnancy, postpartum, and at follow-up 5-11 years later. At follow-up, the women were also examined with a 75-g OGTT or an intravenous glucagon test. Twenty-seven (30%) of the women with previous GDM had abnormal glucose tolerance at follow-up (2 had insulin-dependent diabetes mellitus, 13 had non-insulin-dependent diabetes mellitus, and 12 had impaired glucose tolerance). Compared with the control subjects, women with previous GDM had relatively impaired insulin secretion (decreased insulinogenic index and delayed peak insulin response) at all time points investigated; this was also found when only nonobese glucose-tolerant women were examined. Low insulin secretion during pregnancy together with a high fasting plasma glucose level at the diagnostic OGTT in pregnancy and hyperglycemia during the postpartum OGTT were predictive for subsequent development of overt diabetes (logistic regression analysis). Women who develop GDM have a relative insulin secretion deficiency, the severity of which is predictive for later development of diabetes. Furthermore, our data indicate that their relatively reduced beta-cell function may be a significant pathogenic factor in relation to the high incidence of subsequent diabetes in women with GDM. This could be important in the design of follow-up programs for women with previous GDM.


Analysis of tumor-associated mucin glycotopes by Western transfer methods.
In mucins, glycosylation is complex and the most predominant posttranslational modification. Since mucins exhibit differential glycosylation pattern under physiological and pathological conditions, analysis of mucin glycans is important for understanding their specific functions during pathological conditions like cancer. Given the complexity of mucin glycans, several sophisticated analytical tools such as HPLC, mass spectrometry, and lectin sandwich assays are employed for glyco-analysis of mucins. However the specialized expertise and instrumentation required for such analysis are beyond the reach of an average cancer biology laboratory. We described in this chapter the utility of the simple electrophoresis/immunoblotting method to examine the mucin glycan epitopes, using specific antibodies and lectins.


Calcitonin, an enigmatic hormone: does it have a function?
This editorial presents our view of the status of thyroidal calcitonin (TCT) in mammalian physiology. The discovery of calcitonin (CT) enabled the development of a valuable therapeutic agent but the early experiments most likely misled us with regard to its physiological significance. These early purported roles for TCT, first as an agent important in blood calcium regulation and later as an agent to prevent hypercalcemia, are no longer considered as physiological functions. While large supraphysiological doses of CT have an effect on the morphology and function of osteoclasts, it is unlikely that these effects of CT are important in the normal physiology of osteoclasts or bone remodeling. It is surprising that 38 years after the discovery of TCT there is no consensus as to its role in normal mammalian physiology. This editorial concerns three possibilities with respect to TCT: 1) the hormone is vestigial; 2) the hormone plays a role in water metabolism, ionic concentrations, and/or acid-base balance, actions that may not involve calcium metabolism at all; and 3) TCT acts to store phosphate postprandially on bone surfaces as a labile calcium-phosphate colloid, an action that may provide calcium needed for use in non-feeding periods or to reduce postprandial loss of phosphate when dietary phosphate is limited. Also discussed are recent publications indicating that CT synthesized in non-thyroidal tissues (NTCT) may have paracrine actions.


[Mental pathology in the families of patients with endogenous non-psychotic depression].
Two equal samples each including 23 probands with nonpsychotic depressions within the framework of cyclothymia and sluggish schizophrenia and their relatives of the first degree kinship were examined. It has been established that the cyclothymic proband in the families is at high risk for endogenous affective disorders whereas during sluggish schizophrenia, the risk of mental diseases is not limited by cyclothymia. The probands' relatives may also be attributed to a group at risk for schizophrenia. The data obtained may be interpreted as pathogenetic evidence of the clinical differentiation of endogenous nonpsychotic depressions. Alcoholism and psychopathy loads in the families examined are under discussion.


A qualitative study of a psychiatric emergency.
The psychiatric emergency service (PES) is a major hub in the mental health care delivery system. The aim of this study was to more precisely define what psychiatrists consider to be a psychiatric emergency and to examine the underlying basis of this assessment. Over twenty-two thousand PES visits were assessed prospectively for pertinence and urgency by psychiatrists in four functionally and structurally different services in the province of Quebec, Canada. This study took place between July 15 1996 and August 31, 2004. Overall, 57% of visits were judged pertinent and urgent (P/U), 30% pertinent but not urgent (P/NU) and 13% neither pertinent nor urgent (NP/NU). Between 50 and 60% of P/U tagged visits were diagnosed with an affective or a psychotic disorder, often with a suicidal content. They also more frequently resulted in a short-term observation in the PES or a hospitalization. Variables suggesting the presence of a behaviorally disturbed state (aggressive behaviors, involuntary or police referrals) were equally likely to be found in P/U or NP/NU visits. Legal confinement following the consultation was almost exclusively seen in visits judged P/U. The percent of visits tagged P/U at the four individual sites varied substantially above and below the 57% value for the combined data. Interestingly, no major inter-site differences in diagnostic profiles for the three pertinence and urgency anchor points were found that might account for this variability. Finally, visits from high frequency users were less likely to be judged P/U than visits from patients attending less frequently. Primary consideration for a P/U tag was a visit characterized by a behaviorally disturbed state and/or, suicidal ideation (or attempts) within the context of either an underlying psychotic or affective disorder, especially if poor judgment was an issue. Some specific diagnoses appeared to qualify the above core clinical considerations, increasing or decreasing the probability of a P/U tag. Finally, non-clinical site-specific factors related to the individual services themselves, such as the number of readily available specialized resources, also appeared to qualify this assessment. These data may prove useful for the future development of this service.


The Cryptosporidium parvum transcriptome during in vitro development.
Cryptosporidiosis is caused by an obligate intracellular parasite that has eluded global transcriptional or proteomic analysis of the intracellular developmental stages. The transcript abundance for 3,302 genes (87%) of the Cryptosporidium parvum protein coding genome was elucidated over a 72 hr infection within HCT8 cells using Real Time-PCR. The parasite had detectable transcription of all genes in vitro within at least one time point tested, and adjacent genes were not co-regulated. Five genes were not detected within the first 24 hr of infection, one containing two AP2 domains. The fewest genes detected were at 2 hr post infection, while 30% (985) of the genes have their highest expression at 48 and/or 72 hr. Nine expression clusters were formed over the entire 72 hr time course and indicate patterns of transcriptional increases at each of the 7 time points collected except 36 hr, including genes paralleling parasite 18S rRNA transcript levels. Clustering within only the first 24 hr of infection indicates spikes in expression at each of the 4 time points, a group paralleling 18S rRNA transcript levels, and a cluster with peaks at both 6 and 24 hr. All genes were classified into 18 functional categories, which were unequally distributed across clusters. Expression of metabolic, ribosomal and proteasome proteins did not parallel 18S rRNA levels indicating distinct biochemical profiles during developmental stage progression. Proteins involved in translation are over-represented at 6 hr, while structural proteins are over-represented at 12 hr. Standardization methods identified 107 genes with <80% at a single of its total expression at a single time point over 72 hr. This comprehensive transcriptome of the intracellular stages of C. parvum provides insight for understanding its complex development following parasitization of intestinal epithelial cells.


Omega-3 fatty acid supplementation delays the progression of neuroblastoma in vivo.
Epidemiological and preclinical studies have revealed that omega-3 fatty acids have anticancer properties. We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) induces apoptosis of neuroblastoma cells in vitro by mechanisms involving intracellular peroxidation of DHA by means of 15-lipoxygenase or autoxidation. In our study, the effects of DHA supplementation on neuroblastoma tumor growth in vivo were investigated using two complementary approaches. For the purpose of prevention, DHA as a dietary supplement was fed to athymic rats before the rats were xenografted with human neuroblastoma cells. For therapeutic purposes, athymic rats with established neuroblastoma xenografts were given DHA daily by gavage and tumor growth was monitored. DHA levels in plasma and tumor tissue were analyzed by gas liquid chromatography. DHA delayed neuroblastoma xenograft development and inhibited the growth of established neuroblastoma xenografts in athymic rats. A revised version of the Pediatric Preclinical Testing Program evaluation scheme used as a measurement of treatment response showed that untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response, depending on the DHA concentration. In conclusion, prophylactic treatment with DHA delayed neuroblastoma development, suggesting that DHA could be a potential agent in the treatment of minimal residual disease and should be considered for prevention in selected cases. Treatment results on established aggressive neuroblastoma tumors suggest further studies aiming at a clinical application in children with high-risk neuroblastoma.


Dexamethasone synergistically induces chemotactic peptide receptor expression in HL-60 cells.
We have examined the effect of physiologic concentrations of dexamethasone on the induction of differentiation of the human promyelocytic leukemia cells (HL-60) and the activity of surface receptors for the f-met-leu-phe chemotactic peptide. Dexamethasone at a concentration of 500 nM was markedly synergistic with dimethylformamide and dimethylsulfoxide, but not with trans-retinoic acid, in inducing f-met-leu-phe binding by HL-60 cells. The increase in peptide binding was due to an increase in the activity of peptide receptors rather than an increase in receptor affinity. The effect of dexamethasone was relatively specific for peptide binding as there was little effect when HL-60 differentiation was assessed by cell morphology or the ability of the cells to reduce nitroblue tetrazolium. Dexamethasone alone had no reproducible effect on HL-60 differentiation as assessed by the three criteria tested. The dexamethasone concentration required for half maximal synergism correlated with the known binding constant of the hormone for steroid receptors in HL-60 cells but the effect of dexamethasone was not blocked with the steroid blocking agents 17 alpha methyltestosterone or progesterone.


Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III - convergence toward clinical trials.
Rapid scientific and technological advances have allowed for a more detailed understanding of the relevance of intestinal microbiota, and the entire body-wide microbiome, to human health and well-being. Rodent studies have provided suggestive evidence that probiotics (e.g. lactobacillus and bifidobacteria) can influence behavior. More importantly, emerging clinical studies indicate that the administration of beneficial microbes, via supplementation and/or fecal microbial transplant (FMT), can influence end-points related to mood state (glycemic control, oxidative status, uremic toxins), brain function (functional magnetic resonance imaging fMRI), and mental outlook (depression, anxiety). However, despite the advances in the area of gastro-biological psychiatry, it becomes clear that there remains an urgent need to explore the value of beneficial microbes in controlled clinical investigations. With the history explored in this series, it is fair to ask if we are now on the cusp of major clinical breakthroughs, or are we merely in the quicksand of Autointoxication II?


Nonlinear propagation effects in antiresonant high-index inclusion photonic crystal fibers.
We experimentally and numerically investigate femtosecond-pulse propagation in a microstructured optical fiber consisting of a silica core surrounded by airholes that are filled with a high-index fluid. This fiber combines the resonant properties of hollow-core bandgap fibers and the high nonlinearity of index-guiding waveguides. A range of nonlinear optical effects can be observed, including soliton propagation, dispersive wave generation, and a Raman self-frequency shift. Tuning the center wavelength of the laser and varying the refractive index of the fluid lead to different propagation effects, mediated by the strongly wavelength-dependent group-velocity dispersion in these photonic bandgap confining structures.


Replicating an effective VA program to train and support family caregivers: a hybrid type III effectiveness-implementation design.
Caring for a growing aging population using existing long-term care resources while simultaneously supporting and educating family caregivers, is a public health challenge. We describe the application of the Replicating Effective Programs (REP) framework, developed by the Centers for Disease Control Prevention and used in public health program implementation, to scale up an evidence-based family caregiver training intervention in the Veterans Affairs (VA) healthcare system. From 2018 to 2020, clinicians at eight VA medical centers received REP-guided implementation including facilitation, technical assistance, and implementation tools to deliver the training program. The project team used the REP framework to develop activities across four distinct phases - (1) pre-conditions, (2) pre-implementation, (3) implementation, and (4) maintenance and evolution - and systematically tracked implementation facilitators, barriers, and adaptations. Within the REP framework, results describe how each medical center adapted implementation approaches to fit local needs. We highlight examples of how sites balanced adaptations and intervention fidelity. The REP framework shows promise for national expansion of the caregiver training intervention, including to non-VA systems of care, because it allows sites to adapt while maintaining intervention fidelity. NCT03474380 . Date registered: March 22, 2018.


Integrating patient safety into the clinical microsystem.
Healthcare institutions continue to face challenges in providing safe patient care in increasingly complex organisational and regulatory environments while striving to maintain financial viability. The clinical microsystem provides a conceptual and practical framework for approaching organisational learning and delivery of care. Tensions exist between the conceptual theory and the daily practical applications of providing safe and effective care within healthcare systems. Healthcare organisations are often complex, disorganised, and opaque systems to their users and their patients. This disorganisation may lead to patient discomfort and harm as well as much waste. Healthcare organisations are in some sense conglomerates of smaller systems, not coherent monolithic organisations. The microsystem unit allows organisational leaders to embed quality and safety into a microsystem's developmental journey. Leaders can set the stage for making safety a priority for the organisation while allowing individual microsystems to create innovative strategies for improvement.


The testicular descent in human. Origin, development and fate of the gubernaculum Hunteri, processus vaginalis peritonei, and gonadal ligaments.
Testicular descent has to be divided into the turn-out of the testis and epididymis from the abdomen proper and an inner abdominal descent of genital organs. Both events are closely related to and depend on the development and reorganisation of ligaments, mainly the gubernaculum Hunteri. These seemingly unambiguous events are controversially described since the first description of the gubernaculum, and results and specifics of other species were intermingled with data from humans, thus giving more confusion than lucidity in this important step of gonadal development. Here, we concentrate on human embryos, chronologically investigated by serial sections, scanning electron microscopy, three-dimensional reconstructions, microdissection and immunohistochemistry. The first question to be answered was whether a real inner descent of gonads occurs. We demonstrated this inner descent by showing the relations of the gonads, mesonephros, cranial mesonephric ligament and the anlage of the diaphragm with the vertebral segments. No explosion-like increase in certain vertebral segments was observed which might simulate a gonadal descent. The inner descent is coupled with the growth of the gonad (ovary or testis), the involution of mesonephros, the descending septum transversum or the anlage of the diaphragm, and the intercalated cranial mesonephric ligament. This ligament always inserts medially at the border between the gonad and mesonephros in close relationship to the abdominal ostium of the müllerian duct, a region where hydatides often occur. In contrast to the testes, the ovaries arrive very early--20-25 mm CRL--at their definitive position of S2/3 (level of linea terminalis pelvis), yet, are transversally oriented. The cranial gonadal ligament does not exhibit notable increase in length during inner descent. It does not contain blood vessels. While regressing in both sexes, it will be replaced by the plica formed by the ovarian vessels, that is the suspensorium ligament of the ovary as known in adults. The second point to be investigated was the origin, development, structure and fate of the gubernaculum Hunteri as well as the processus vaginalis peritonei. Their arrangement and composition is crucial for testicular descent. We discriminated five phases of their development and differentiation. Phase I characterises the early development of the gubernaculum of stage 14 CC (5-7 mm CRL) embryos. It arises as conus inguinalis and connects the abdominal wall lateral to the umbilical artery with the caudal part of the mesonephric fold. It is in this early stage that the localisation of the inner inguinal ring is defined. In phase II, stage 20-23 CC (21-30 mm CRL), three parts of the gubernaculum--abdominal, interstitial and subcutaneous--can be distinguished. The processus vaginalis peritonei appears with its dorsal layer firmly adhering to the ventral side of the gubernaculum. The gubernaculum inserts cranially into the mesenchyme of the genital ducts at their crossing-over. Opposite to it, but at some distance, a ligament connects the caudal pole of the testis with the dorsal mesenchyme of the genital ducts. In female embryos, the analge of the ovarian ligament appears as a U-shaped, double peritoneal fold. Phase II is subdivided in phase IIa (32-55 mm CRL), characterised by an enormous increase in length and volume of the gubernaculum and also an enlargement of the processus vaginalis peritonei. In phase III, sex-specific differences in gonadal position and gubernacular structure can be observed for the first time. Testes increase in volume and come close to the mesenchyme of the genital ducts. The caudal pole of the testis overlaps both ducts. We also subdivide this phase into phase IIIa (about 100 mm CRL) where two very important events occur in male foetuses: 1, the swelling of the gubernaculum, and 2, the gliding of the testis across the genital ducts. This gliding is permitted by both, the regression of the müllerian duct and t


Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.
Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.


Rapidly progressive acute chest syndrome in individuals with sickle cell anemia: a distinct acute chest syndrome phenotype.
Current definitions of acute chest syndrome (ACS) in sickle cell anemia (SCA) do not account for rapid progression of respiratory compromise. In this two-center retrospective cohort study, we tested the hypothesis that in children and adults with ACS and respiratory failure (≤24 hours after onset of respiratory symptoms) have a distinct ACS phenotype associated with multiorgan failure when compared to those with ACS that have a more subacute and protracted course. We identified 173 individuals (97 children <20 years and 76 adults ≥20 years) with SCA and at least one episode of ACS. Only one ACS episode was considered per individual. Rapidly progressive ACS occurred in 21% (n = 16) of adults, but only 2.1% (n = 2) of children. Compared to adults without rapidly progressive ACS, adults with rapidly progressive ACS more frequently developed acute kidney injury (68.8% vs. 3.3%, P < 0.001), hepatic dysfunction (75.0% vs. 15.0%, P < 0.001), altered mental status (43.8% vs. 11.7%, P < 0.001), multiorgan failure (93.8% vs. 10%, P < 0.001), and death (6.3% vs. 0%, P = 0.05). Clinical and laboratory covariates that were evaluable on the first day of respiratory symptoms were evaluated to identify predictors of rapidly progressive ACS. On multivariable analysis, decline in platelet count at presentation was the only predictor of rapidly progressive ACS [odds ratio 4.82 (95% CI 1.20-19.39), P = 0.027]. In conclusion, rapidly progressive ACS is a distinct phenotype that occurs more frequently in adults, is preceded by thrombocytopenia, and is associated with multiorgan failure. Am. J. Hematol. 91:1185-1190, 2016. © 2016 Wiley Periodicals, Inc.


The N-terminal hydrophobic region of the mature phosphate translocator is sufficient for targeting to the chloroplast inner envelope membrane.
To locate the sequence required for directing the phosphate translocator to the chloroplast inner envelope membrane, a series of chimeric proteins constituting parts of the phosphate translocator and the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, which is normally located in the stroma, has been produced. Reciprocal exchanges of the presequences and mature sequences of the phosphate translocator and the small subunit indicated that the phosphate translocator presequence contains stromal targeting information and that the mature protein is responsible for inner envelope membrane targeting. Chimeric proteins containing the N-terminal 46 amino acid residues of the phosphate translocator were directed to the inner envelope membrane. Subdivision of this region into its composite hydrophilic and hydrophobic regions showed that the hydrophobic region alone, which consists of amino acid residues 24 to 45, was able to direct the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase to the inner envelope membrane.


De Novo transcriptome assembly (NGS) of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids.
Herbal remedies are increasingly being recognised in recent years as alternative medicine for a number of diseases including cancer. Curcuma longa L., commonly known as turmeric is used as a culinary spice in India and in many Asian countries has been attributed to lower incidences of gastrointestinal cancers. Curcumin, a secondary metabolite isolated from the rhizomes of this plant has been shown to have significant anticancer properties, in addition to antimalarial and antioxidant effects. We sequenced the transcriptome of the rhizome of the 3 varieties of Curcuma longa L. using Illumina reversible dye terminator sequencing followed by de novo transcriptome assembly. Multiple databases were used to obtain a comprehensive annotation and the transcripts were functionally classified using GO, KOG and PlantCyc. Special emphasis was given for annotating the secondary metabolite pathways and terpenoid biosynthesis pathways. We report for the first time, the presence of transcripts related to biosynthetic pathways of several anti-cancer compounds like taxol, curcumin, and vinblastine in addition to anti-malarial compounds like artemisinin and acridone alkaloids, emphasizing turmeric's importance as a highly potent phytochemical. Our data not only provides molecular signatures for several terpenoids but also a comprehensive molecular resource for facilitating deeper insights into the transcriptome of C. longa.


Prevalence and factors associated with the occurrence of bacterial enteropathogens in suckling piglets in farrow-to-finish herds.
The aim of the study was to determine both environmental and infectious factors, influencing occurrence of bacterial enteropathogens in suckling piglets. For this purpose, a cross-sectional study in 70 Polish farrow-to-finish pig herds was performed. In each herd, presence of selected intestinal pathogens (Escherichia coli, Clostridium perfringens and Salmonella species) in faeces of suckling piglets were determined using bacteriological and PCR methods. Using logistic regression models, risk factors for enterotoxigenic E coli with fimbriae F4 (ETEC-F4) and C perfringens type A were established. Prevalence of bacterial enteropathogens in investigated herds was as follows (on herd and sample level): ETEC-F4 30.0 per cent and 9.3 per cent, respectively, C perfringens type A 91.4 per cent and 58.3 per cent, C perfringens type C 1.4 per cent and 0.3 per cent, Salmonella species 2.9 per cent and 0.5 per cent. The occurrence of ETEC-F4 was associated with presence of diarrhoea in piglets and vulval discharge in sows. Vulval discharge in sows, not slatted floor in farrowing pen and lack of coccidiosis prevention were determined as risk factors for C perfringens type A. The results obtained in the study revealed the high prevalence of enteropathogenic bacteria in pig herds and indicate management and organisation of production as factors having the greatest impact on the incidence of bacterial enteropathogens in piglets before weaning.


Reduction of TMS induced artifacts in EEG using principal component analysis.
Co-registration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a new, promising method for assessing cortical excitability and connectivity. Using this technique, a TMS evoked potential (TEP) can be induced and registered with the EEG. However, the TEP contains an early, short lasting artifact due to the magnetic pulse, and a second artifact, which depends on the location of stimulation and can last up to 40 ms. Different causes for this second artifact have been suggested in literature. In this study, we used principal component analysis (PCA) to suppress both the first and second artifact in TMS-EEG data. Single pulse TMS was applied at the motor and visual cortex in 18 healthy subjects. PCA using singular value decomposition was applied on single trials to suppress the artifactual components. A large artifact suppression was realized after the removal of the first five PCA components, thereby revealing early TEP peaks, with only a small suppression of later TEP components. The spatial distribution of the second artifact suggests that it is caused by electrode movement due to activation of the temporal musculature. In conclusion, we showed that PCA can be used to reduce TMS-induced artifacts in EEG, thereby revealing components of the TMS evoked potential.


Effect of Gamma Irradiation on Cannabinoid, Terpene, and Moisture Content of Cannabis Biomass.
In recent years, cannabis has been proposed and promoted not only as a medicine for the treatment of a variety of illnesses, but also as an industrial crop for different purposes. Being an agricultural product, cannabis inflorescences may be contaminated by environmental pathogens at high concentrations, which might cause health problems if not controlled. Therefore, limits have to be placed on the levels of aerobic bacteria as well as yeast and mold. To ensure the safety of cannabis plant material and related products, a remediation process has to be put in place. Gamma irradiation is a sterilization process mainly used for pharmaceuticals, foods, cosmetics, agricultural, and herbal products including cannabis plant material. This study was designed to determine the effect of irradiation on the microbial count as well as on the chemical and physical profiles of the cannabis biomass, particularly cannabinoids, terpenes, and moisture content. The full cannabinoid profile was measured by GC/FID and HPLC analysis, while terpene profile and moisture content were determined using GC/MS and Loss on Drying (LoD) methods, respectively. Analyses were conducted on the samples before and after gamma irradiation. The results showed that the minimum and maximum doses were 15 and 20.8 KiloGray (KGY), respectively. Total Aerobic Microbial Count (TAMC) and Total Yeast and Mold Count (TYMC) were determined. The study showed that irradiation has no effect on the cannabinoids and little effect on terpenes and moisture content, but it did result in the virtual sterilization of the plant material, as evidenced by the low levels of bacterial and fungal colony-forming units (CFUs) < 10 after gamma irradiation.


Polyhydroquinoline derivatives for diabetic management: synthesis, in vitro and in silico approaches.
Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives (1-17) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC50 values from 1.23 ± 0.03 to 73.85 ± 0.61 μM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.


Catalytic CO2 reduction to valuable chemicals using NiFe-based nanoclusters: a first-principles theoretical evaluation.
Converting CO2 into valuable chemicals and fuels is one of the most practical routes for reducing CO2 emissions while fossil fuels continue to dominate the energy sector. Noble-metal-free NiFe bimetal nanoparticles have shown good catalytic activity in CO2 conversion. Herein we theoretically evaluated the catalytic performance and possible mechanisms of NiFe-based nanoclusters for hydrogenating CO2 to form formic acid and CO through bicarbonate by using a periodic and self-consistent density functional theory (DFT) simulation. The theoretical results illustrated that NiFe nanoclusters could have good catalytic activity and selectivity for HCO3- reduction to formic acid and the possible pathway is that HCO3- preferred to react with adsorbed H atoms of H2 on NiFe alloy nanoclusters through the carbon atom site. Moreover, the NiFe alloy nanoclusters with the Fe atom exposed on the surface of the Ni cluster showed better performance with a lower energy barrier compared to that with Fe doped in the corner of the Ni cluster. However, the generation of CO from HCO3- reduction was shown to be neither thermodynamically nor kinetically favorable on NiFe alloy nanoclusters. Additionally, the simulation results also suggested that it was thermodynamically unfavorable for further hydrogenated reduction of formic acid to formaldehyde on NiFe alloy nanoclusters themselves as well as supported on graphene. In summary, a molecular-level insight of CO2 reduction to valuable products on NiFe nanoclusters is offered in this study, which may provide some useful information for guiding the design of NiFe-based catalytic materials for efficient CO2 conversion to useful fuels.


Chylous ascites following resection of a ruptured abdominal aneurysm. Treatment with a peritoneovenous shunt.
The development of chylous ascites after an abdominal surgical procedure is potentially grave. It frequently leads to malnutrition and significant mortality. Chylous ascites developed after emergency repair of a ruptured abdominal aneurysm. In spite of treatments with low-fat diet (medium-chain triglycerides), hyperalimentation, and abdominal paracentesis, hypoproteinemia and peripheral edema developed and symptomatic ascites continued. Though some success has been reported following ligation of leaking lymphatics, we avoided laparotomy because the patient was recovering from formidable complications. A peritoneovenous shunt was placed. No complications occurred and permanent recovery promptly resulted. We believe this is a reasonable alternative to laparotomy.


The identification of microRNAs in calcisponges: independent evolution of microRNAs in basal metazoans.
We present the discovery of microRNAs (miRNAs) in the calcisponges Sycon and Leucosolenia (phylum Calcarea), and potential miRNAs in the homoscleromorph Oscarella carmela (Phylum Homoscleromorpha), expanding the complement of poriferan miRNAs previously known only from the siliceous sponges (demosponges and hexactinellids). Comparison of these miRNAs with those previously described from silicisponges and eumetazoans reveals that these newly described miRNAs are novel, with each metazoan lineage (Silicea, Calcarea, Homoscleromorpha, and Eumetazoa) characterized by a unique and non-overlapping repertoire of miRNAs (or potential miRNAs as in the case of the homoscleromorphs). Because each group is characterized by a unique repertoire of miRNAs, miRNAs cannot be used to help resolve the contentious issue of sponge mono- versus paraphyly. Further, because all sponges are characterized by a similar repertoire of tissue types and body plan organisation, we hypothesize that the lack of conserved miRNAs amongst the three primary sponge lineages is evidence that cellular differentiation and cell type specificity in sponges are not dependent upon conserved miRNAs, contrary to many known cases in eumetazoans. Finally, we suggest that miRNAs evolved multiple times independently not only among eukaryotes, but even within animals, independently evolved miRNAs representing molecular exaptations of RNAi machinery into pre-existing gene regulatory networks. The role(s) miRNAs play though in sponge biology and evolution remains an open question.


Uncemented femoral stem design influences the occurrence rate of postoperative fractures after primary hip arthroplasty: a comparison of the Image and Profile stems.
Two consecutive series of hip arthroplasties with closely similar anatomic uncemented femoral implants [207 Profile (DePuy) and 171 Image (Smith&Nephew) stems] were compared with regard to postoperative femoral fractures. All arthroplasties were performed by senior staff surgeons, mainly on patients below 65 years of age. In the Image group the occurrence rate of postoperative periprosthetic femoral fractures was higher (9.36%) compared to the Profile group (2.99%) and fractures occurred earlier (1.69 y vs. 8.84 y). The bulkier proximal part, the thinner cylindrical distal two thirds and the larger offset probably resulted in less rotational stability and increased proximal torsional load transfer during activities of daily living. This resulted in femoral fractures after minor trauma, without osteolysis. This study emphasizes the need for close follow-up when introducing new implants, even if they rely on known principles and feature only minor changes from proven concepts.


Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.
Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.


Extension and acceleration of relativistic density functional theory based on transformed density operator.
We report an extension of relativistic density functional theory (RDFT) within one-component or two-component expressions that relies on a unitary-transformed density operator as well as a unitary-transformed Hamiltonian [Oyama et al., Chem. Phys. Lett. 680, 37 (2017)]. The transformed density operator is introduced to avoid the picture-change effect in the electron density, density gradient, kinetic energy density, and exchange-correlation potential. We confirmed that the implementation based on the spin-free infinite-order Douglas-Kroll-Hess method gives total, orbital, and excitation energies close to the reference values given by four-component RDFT calculations. To reduce the computational cost due to the transformed density operator, the local unitary transformation was also implemented. Numerical assessments revealed that the present scheme enabled the RDFT calculation of polyatomic systems with negligibly small picture-change effect.


The continued ageing of people with AIDS in Italy: recent trend from the national AIDS Registry.
Introduction. In industrialized countries, the availability of highly active antiretroviral therapy (HAART) caused a slow but substantial ageing of the AIDS epidemic mainly due to the longer survival of persons with HIV/AIDS which has turned HIV into a manageable, chronic disease. The number of older people with AIDS is growing in many European countries. We described the impact of AIDS among persons aged 50 years or more in Italy and compared the characteristics of these cases with those of persons diagnosed with AIDS at an age younger than 50. Methods. The source of data was the Italian AIDS Registry, from 1982 to 2011. We defined "older" persons those aged 50 years or more, and younger individuals those aged less than 50 years. We built two multivariate logistic regression models: the first one to identify factors associated with being older, and the second one to identify AIDS-defining diseases correlated with being older. Variables with a P value of <0.05 were entered in the model. Results. Of the total AIDS cases, 10.5% were among persons older than 49 years. This proportion progressively increased from 0.0% in 1983 to 26.4% in 2011. Among older cases, the incidence of AIDS was 2.0 per 100 000 residents in 1996, then decreased to 1.4 per 100 000 in 2000 and levelled off around 1 per 100 000 residents until 2011. Compared to younger cases, older cases were more frequently males, Italians, diagnosed with AIDS in recent years, residing in Northern or Central Italy, non-injecting drug users, and late testers. Discussion. These findings stress the need for physicians to consider carefully the possibility of HIV infection among older individuals not to miss the opportunity to deliver prevention messages, offer HIV testing, and make an early diagnosis.


Optical Coherence Tomography in Multiple Sclerosis.
Retinal optical coherence tomography (OCT) has recently become a vital tool for clinicians and researchers in ophthalmology and, increasingly, in neurology. Optical coherence tomography is quickly and easily performed, well-tolerated by patients, and allows high-resolution viewing of unmyelinated axons and other retinal structures in vivo. These factors have led OCT to find favor as a method of quantifying neuroaxonal loss in multiple sclerosis (MS), and the increasing acceptance of the anterior visual pathway as a model to investigate MS in humans.In this short review, the authors discuss OCT findings in MS research, and the relationships of these structural findings with established functional outcome measures such as visual acuity and electrophysiological examinations. The utility of OCT in patients with acute optic neuritis is emphasized. Optical coherence tomography is a particularly powerful tool when the individual retinal layers are visualized and quantified following the segmentation of scans; this technique shows promise as a method for defining novel MS phenotypes.


Consequences of continuous ozonation on the health and welfare of Atlantic salmon post-smolts in a brackish water recirculating aquaculture system.
This study investigated the biological consequences of 45-day continuous ozonation on Atlantic salmon (Salmo salar) post-smolts in a brackish water recirculating aquaculture system (RAS). There was no significant difference in survival, operational welfare indicators, and average weight at termination between the ozone-treated and control groups. Plasma biochemical analyses revealed that the creatinine level was significantly higher in the ozone-treated group than in the control at termination. Histological evaluation of skin health showed no significant difference between the two groups. On the other hand, quantitative histopathology disclosed that the ozone group exhibited a better gill health status than did the control group, particularly at the end of the trial. Mucosal transcriptomics revealed a distinct response profile between the gills and skin. At day 45, there were no differentially expressed genes (DEG) identified in the skin, in contrast to 242 ozone-induced DEGs in the gills. Assessment of the transcriptomic profiles over time revealed that temporal effects were of greater impact in skin compared to gills, regardless of the treatment. The treatment did not result in metabolomic dysregulation and the overall profile lent support to the transcriptomics data that temporal effects had a greater influence on the changes observed. Exposure to handling-confinement stress revealed that ozone treatment did not alter the ability of post-smolts to respond to a secondary stressor. In summary, the suite of health and welfare indicators collectively indicated that continuous ozonation resulted in minimal physiological perturbations in salmon post-smolts. The results are expected to contribute to optimising the rearing conditions for post-smolts in RAS.


Holey random walks: optics of heterogeneous turbid composites.
We present a probabilistic theory of random walks in turbid media with nonscattering regions. It is shown that important characteristics such as diffusion constants, average step lengths, crossing statistics, and void spacings can be analytically predicted. The theory is validated using Monte Carlo simulations of light transport in heterogeneous systems in the form of random sphere packings and good agreement is found. The role of step correlations is discussed and differences between unbounded and bounded systems are investigated. Our results are relevant to the optics of heterogeneous systems in general and represent an important step forward in the understanding of media with strong (fractal) heterogeneity in particular.


Glucocorticoid modulation of human monocyte/macrophage function: control of TNF-alpha secretion.
Glucocorticoids suppress many functions in activated monocyte/macrophages, including the release of TNF-alpha. This is likely to contribute to the efficacy of glucocorticoids in some inflammatory diseases, such as rheumatoid arthritis, where TNF-alpha contributes to pathogenesis. Glucocorticoids suppress the activity of reporters which include TNF-alpha promoter regions and modify the activity of NF-kappa B family transcription factors in activated human monocytic cell lines, suggesting effects of glucocorticoids on TNF-alpha gene transcription. In addition, glucocorticoids have been reported to antagonise the enhanced translational efficiency of TNF-alpha mRNA which occurs at least after stimulation of murine monocytic cells. It is likely, therefore, that glucocorticoids act at several points in stimulated monocyte/ macrophages to reduce TNF-alpha secretion. Understanding glucocorticoid control of TNF-alpha secretion may explain some of the variability in response to GC in inflammatory diseases and may reveal means of inducing glucocorticoid-like anti-inflammatory effects in monocyte/macrophages without exposing other tissues to the adverse effects of glucocorticoids.


Dental implant systems.
Among various dental materials and their successful applications, a dental implant is a good example of the integrated system of science and technology involved in multiple disciplines including surface chemistry and physics, biomechanics, from macro-scale to nano-scale manufacturing technologies and surface engineering. As many other dental materials and devices, there are crucial requirements taken upon on dental implants systems, since surface of dental implants is directly in contact with vital hard/soft tissue and is subjected to chemical as well as mechanical bio-environments. Such requirements should, at least, include biological compatibility, mechanical compatibility, and morphological compatibility to surrounding vital tissues. In this review, based on carefully selected about 500 published articles, these requirements plus MRI compatibility are firstly reviewed, followed by surface texturing methods in details. Normally dental implants are placed to lost tooth/teeth location(s) in adult patients whose skeleton and bony growth have already completed. However, there are some controversial issues for placing dental implants in growing patients. This point has been, in most of dental articles, overlooked. This review, therefore, throws a deliberate sight on this point. Concluding this review, we are proposing a novel implant system that integrates materials science and up-dated surface technology to improve dental implant systems exhibiting bio- and mechano-functionalities.


Mean diffusivity associated with trait emotional intelligence.
Previous neuroimaging studies have suggested that the neural bases of trait emotional intelligence (TEI) lie in the social cognition network (SCN) and the somatic marker circuitry (SMC). The current study was the first to investigate the associations of total TEI factors and subfactors with mean diffusivity (MD) of these networks as well as regional MD of the dopaminergic system (MDDS). We found that TEI intrapersonal factor score and total TEI score were negatively correlated with regional MDDS in the vicinity of the right putamen and right pallidum and that TEI intrapersonal factor score was negatively correlated with MD values of the fusiform gyrus. Total TEI score and TEI factor scores were positively correlated with MD values of various areas within or adjacent to SCN components, SMC structures and the lateral prefrontal cortex (LPFC). Our MD findings demonstrated the importance of the dopaminergic system to TEI and implicate the SCN, SMC and LPFC in TEI. Future studies are required to investigate the implications of positive and negative associations with MD values.


Examining and Extending the Influence of Presumed Influence Hypothesis in Social Media.
The influence of presumed influence hypothesis (IPI) is a communication theory accounting for the process of persuasive media effects. The present study integrates theoretical perspectives in persuasion and new and traditional media effects research to investigate the assumptions and explanatory mechanisms of IPI in an experiment. View numbers in social media directly predicted presumed exposure by others and indirectly predicted presumed influence on others, consistent with IPI and inconsistent with the bandwagon heuristic. Presumed exposure predicted presumed influence, consistent with IPI. Other predictors of presumed exposure and presumed influence were also found. Self's evaluation of the message (realism) and engagement in the message (identification) predicted presumed exposure by others and presumed influence on others, supporting the expectation that a motivational mechanism of IPI is self-centric social perception. Social media message view numbers did not predict persuasive outcomes directly, but the evaluation of and engagement in the message did. Finally, the data were inconsistent with the assumption of pervasive mass media reach. This study provides theoretical implications for examining persuasive effects of social media messages, while enhancing and expanding IPI. Limitations of the study and directions for future research are discussed.


Insight into the pathogenesis of fetal growth restriction in placental malaria: decreased placental glucose transporter isoform 1 expression.
Placental malaria, especially when complicated with intervillositis, can cause fetal growth restriction. Transplacental glucose transport by glucose transporter isoform 1 (GLUT-1) on the syncytiotrophoblast microvillous and basal plasma membranes regulates fetal growth. We found that GLUT-1 expression in the microvillous plasma membrane of Plasmodium falciparum-negative placenta biopsy specimens was comparable to that in P. falciparum-positive placenta biopsy specimens with or without intervillositis, whereas GLUT-1 expression in the basal plasma membrane was lowest in P. falciparum-positive placenta biopsy specimens with intervillositis, compared with the other 2 specimen types (P ≤ .0016). GLUT-1 expression in the basal plasma membrane also correlated negatively with monocyte infiltrate density (r = -0.43; P = .003) and positively with birth weight (r = 0.28; P = .06). These findings suggest that intervillositis, more than placental malaria per se, might cause fetal growth restriction, through impaired transplacental glucose transport.


Anatomy teaching for medical undergraduates: general practice as a guideline? The brain.
Basic science teaching, particularly the teaching of gross anatomy, is at present a highly controversial topic. How much and what kind of anatomy should be taught to medical undergraduates nowadays? In conducting the present study we based our proposals on the criterion of general medical relevance. Therefore, we sent an anatomical questionnaire to a sample of Swiss general practitioners. Here, we present the results derived from questions on the human brain, discussing them in connection with the other organs so far investigated. The results obtained suggest that a common body of anatomical knowledge appropriate for the field of general medical practice does in fact exist. We believe that this basic stock can serve as a guideline for decision makers involved in the development of curricula, which can be fitted into the time frame available for anatomy teaching today while still guaranteeing a sound level of competence required for general practice of medicine. We also hope that this approach may serve as a model for the teaching of other basic sciences.


Granulomatous enterocolitis induced in rats by purified bacterial cell wall fragments.
This study was designed to determine if poorly biodegradable bacterial cell wall components can produce chronic intestinal inflammation. A sterile aqueous suspension of sonically disrupted group A or group D streptococcal cell wall fragments was injected intramurally into the small intestine and cecum of 100 rats. Gross findings in rats killed at intervals of 1 day to 6 mo included intestinal thickening, adhesions, and mesenteric contraction. Acute histologic inflammation subsided by 2 wk, but chronic granulomatous inflammation persisted for 6 mo in the rats injected with group A streptococcal cell wall fragments and 3 mo in the rats injected with group D streptococcal cell wall fragments. Ninety-six control rats identically injected with human serum albumin or phosphate-buffered saline demonstrated mild acute inflammation that resolved, with only 1 rat having chronic intestinal inflammation. Granulomas in the intestine, mesentery, and mesenteric lymph nodes developed in 46% of the rats injected with group A fragments and 45% of the rats injected with group D streptococcal cell wall fragments, compared with 20% of the controls injected with albumin and 4% of the controls injected with phosphate-buffered saline. Group A streptococcal antigen was detected by immunofluorescence at the site of inflammation for 4 mo, and possible reactivation of acute inflammation was seen up to 6 mo after injection. We conclude that bacterial cell wall fragments are capable of producing chronic granulomatous inflammation in the intestinal wall if present in appropriate particle size and concentration. We speculate that cell walls from the enteric microflora may leak across a permeable mucosa in chronic inflammatory bowel disease to initiate and sustain local and systemic inflammation.


Effects of Carthamus tinctorius L. on the ovarian histomorphology and the female reproductive hormones in mice.
Carthamus tinctorius L. (Safflower) is a member of the asteraceae family which had been classified as a fertility regulator in the traditional medicine. The purpose of this study was to investigate its possible effects on the ovarian histomorphology and the levels of female reproductive hormones in the mice. Sixty adult female Balb/C mice were selected and randomly divided into one control and three experimental groups (n= 15). The control group received only distilled water, while experimental groups were administered intraperitoneally C. tinctorius extract at doses of 0.7, 1.4, and 2.8 mg/kg/day for 49 consecutive days. In the end of experiments, blood samples were collected and the sera were analyzed for the levels of FSH, LH, estrogen, and progesterone. Ovarian tissue samples were also taken and histomorphological changes of the ovaries were examined using optical microscope. The quantitative results were statistically analyzed by one-way ANOVA test. The present findings showed that treatment with different concentrations of C. tinctorius extract reduced the number of ovarian follicles but number of atretic follicles showed an increase. The number and size of the corpora lutea were not affected by extract administration. In addition, in the treated mice with C. tinctorius extract, the thickness of the tunica albuginea was increased but the relative and absolute weights of the ovaries decreased significantly. Furthermore, the blood levels of the FSH and estrogen were decreased in the three experimental groups compared with those of the control animals. The present findings indicated that treatment with C. tinctorius extract has detrimental effects on the ovarian histomorphology and female reproductive hormones therefore popular consumption of this plant should be reconsidered.


Use of surveillance imaging following treatment of small renal masses.
With the increasing incidence of small renal masses, there is greater use of ablation, nephron sparing surgery and surveillance compared to radical nephrectomy. However, patterns of care in the use of posttreatment imaging remain uncharacterized. The purpose of this study is to determine the rate of posttreatment imaging after various treatments for small renal mass. Using SEER (Surveillance, Epidemiology and End Results)-Medicare data during 2005 to 2009, we identified 1,682 subjects diagnosed with small renal mass and treated with open partial nephrectomy (330), minimally invasive partial nephrectomy (160), open radical nephrectomy (404), minimally invasive radical nephrectomy (535), thermal ablation (212) and surveillance (42). Use of imaging was compared within 24 months of treatment and multivariate regression models were constructed to identify factors associated with increased imaging use. On adjusted analyses thermal ablation was associated with almost eightfold greater odds of surveillance imaging compared with open radical nephrectomy (OR 7.7, 95% CI 1.01-59.4). Specifically, thermal ablation was associated with increased computerized tomography (OR 5.28) and magnetic resonance imaging (OR 2.19) use and decreased ultrasound use (OR 0.59). Minimally invasive partial nephrectomy (OR 3.28) and open partial nephrectomy (OR 3.19) were also associated with increased computerized tomography use to a lesser extent. Subjects undergoing nephron sparing surgery undergo more posttreatment imaging compared to open radical nephrectomy. Although possibly associated with lower morbidity, thermal ablation is associated with significantly greater use of imaging compared to other small renal mass treatments. This may increase costs and radiation exposure, although further study is needed for confirmation.


Toward N-peri-Annulated Planar Blatter Radical through aza-Pschorr and Photocyclization.
Preparation of the elusive N-peri-annulated planar Blatter radicals was attempted using aza-Pschorr and photocyclization methods. In both methods, substrates containing N-Me and N-Ac groups yielded a zwitterionic heterocycle lacking the N-substituent as the main product, while in one of them a carbazole derivative representing a new heterocyclic system was also obtained. The formation of the zwitterion and the carbazole suggests the formation of the desired planar Blatter radical, which undergoes facile fragmentation through homolysis of the N-R bond. This mechanism is supported by DFT computational results, which also suggest that N-Ar derivatives should be sufficiently stable for isolation. Electronic structures of three planar Blatter radicals annulated with the O, S, and N-Ph groups are compared.


Placement and Format of Risk Information on Direct-to-Consumer Prescription Drug Websites.
We investigated whether the location and format of risk information on branded prescription drug websites influence consumers' knowledge and perceptions of the drug's risks. Participants (Internet panelists with high cholesterol [n = 2,609] or seasonal allergies [n = 2,637]) were randomly assigned to view a website promoting a fictitious prescription drug for their condition. The website presented risk information at the bottom of the homepage, or at the bottom of the homepage with a signal above indicating that the risk information was located below, or on a linked secondary page. We also varied the format of risk information (paragraph, checklist, bulleted list, highlighted box). Participants then answered questions on risk recall and perceptions. Participants recalled fewer drug risks when the risks were placed on a secondary page. The signal had little effect, and risk information format did not affect outcomes. The location of risk information on prescription drug websites can affect consumer knowledge of drug risks; however, signals and special formatting may not be necessary for websites to adequately inform consumers about drug risks. We recommend that prescription drug websites maintain risk information on their homepages to achieve "fair balance" as required by the U.S. Food and Drug Administration.


Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus.
This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. A total of 383 individuals, aged 48.3 ± 16.2 years, with 54.1% women, and a remnant cholesterol level of 16 ± 10 mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (p = 0.015) and more time above the target range (p = 0.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30 mg/dL, OR 8.93, 95% CI (2.99-26.62), p < 0.001. Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes.


Pre-slaughter conditions, animal stress and welfare: current status and possible future research.
The present paper describes the main procedures used to slaughter fowl, pigs, calves and adult cattle, sheep, and farmed fish, starting on the farm and ending with the death of the animal at the abattoir. It reviews the currently known causes of stress, indicated by behavioural and physiological measurements on the animal level, and by post-mortem muscle metabolism. During the pre-slaughter period, psychological stress is due to changes of environment, social disturbances and handling, and physical stress is due to food deprivation, climatic conditions, fatigue, and sometimes pain. The exact causes of stress depend, however, on the characteristics of each species, including the rearing system. For fowl, bird catching and crating, duration and climatic conditions of transport and of lairage and shackling are the main known pre-slaughter stress factors. For pigs, stress is caused by fighting during mixing of pens, loading and unloading conditions, and introduction in the restrainer. Handling and novelty of the situation contribute to the stress reactions. For veal calves and adult cattle, disruption of the social group, handling, loading and sometimes unloading conditions, fatigue, novelty of the situation and for calves mixing with unfamiliar animals are known stress factors. Gathering and yarding of extensively reared lambs and sheep causes stress, particularly when shepherd dogs are used. Subsequent transport may induce fatigue, especially if sheep are commercialised through auctions or markets. In farmed fish, stress is predominantly related to environmental aspects such as temperature, oxygen, cleanliness of the water and, to a certain extent, stocking density and removal of the fish from the water. If transport and lairage conditions are good and their durations not too long, they may allow pigs, calves and adult cattle, sheep, and fish to rest. For certain species, it was shown that genetic origin and earlier experience influence reactions to the slaughter procedure. Stunning techniques used depend on the species. Pigs and fowl are mostly electrically or gas-stunned, while most adult cattle are stunned with a captive bolt pistol. Calves and sheep may be electrically stunned or with a captive bolt pistol. Various stunning methods exist for the different farmed fish species. Potential causes of stress associated with the different stunning procedures are discussed. The paper addresses further consequences for meat quality and possible itineraries for future research. For all species, and most urgently for fish, more knowledge is needed on stunning and killing techniques, including gas-stunning techniques, to protect welfare.


Anti-HER3 domain 1 and 3 antibodies reduce tumor growth by hindering HER2/HER3 dimerization and AKT-induced MDM2, XIAP, and FoxO1 phosphorylation.
Blockade of the human epidermal growth factor receptor 3 (HER3) and of the downstream phosphatidylinositide 3-kinase (PI3K)/AKT pathway is a prerequisite for overcoming drug resistance and to develop novel treatments for cancers that are not eligible for the currently approved targeted therapies. To this end, we generated specific antibodies (Abs) against domain 1 (D1) and domain 3 (D3) of HER3 that recognize epitopes that do not overlap with the neuregulin-binding site. The fully human H4B-121 Ab and the mouse monoclonal Abs 16D3-C1 and 9F7-F11 inhibited tumor growth in nude mice xenografted with epidermoid, pancreatic, or triple-negative breast cancer cells. The combination of one anti-HER3 Ab and trastuzumab improved tumor growth inhibition in mice xenografted with HER2(low) cancer cell lines, for which trastuzumab alone shows no or moderate efficiency. Ab-induced disruption of tumor growth was associated with G1 cell cycle arrest, proliferation inhibition, and apoptosis of cancer cells. Anti-HER3 Abs blocked HER2/HER3 heterodimerization and HER3 phosphorylation at the cell membrane, leading to inhibition of phosphorylation of the downstream AKT targets murine double minute 2, X-linked inhibitor of apoptosis, and forkhead box O1. This study demonstrates that anti-HER3 D1 and D3 Abs could represent a new option for immunotherapy of pancreatic and triple-negative breast cancers.


A Rare Case of Giant Cell Tumour of Bilateral Achilles Tendon Sheath - Reconstruction with Dual Tendon Transfer: A Case Report.
Giant cell tumour of tendon sheath is a benign soft tissue lesion most commonly found in the flexor aspect of hand and wrist. However, it is uncommon in foot and ankle and rare in bilateral achilles tendon. We report a case of 17-year-old female who presented with progressive enlargement of bilateral achilles tendon for six months. MRI findings showed that most of the tumour had intermediate to low signal intensity. Histopathology confirmed the diagnosis of giant cell tumour of tendon sheath. To help the patient regain the strength of the achilles tendon and walking abilities, a large area of tendon tumour was excised, followed by reconstruction with transfer of the peroneus brevis (PB) and posterior tibial (PT) tendon autograft. At two years follow-up, functional result was satisfactory.


Should general practitioners have any role in maternity care in the future?
Maternity services in England are currently being reorganized. The success of the changes will be judged against the recommendations of the Changing Childbirth report. This paper describes the nature of maternity care and of general practice. It is argued that maternity care provision by general practitioners is a central and essential part of British general practice. Specifically, it is shown how general practitioners can help to achieve the objectives of the report, and thus, have a future role. It is suggested that all general practitioners who wish maternity care to remain an essential part of general practice need to argue the case with providers and purchasers. If they do not, then it is quite likely that general practitioners will be increasingly excluded as the commissioning and contracting mechanisms become more effective with midwives providing low-risk care and consultant obstetricians high-risk care.


Information about age-related macular degeneration on the Internet.
A great deal of health information has become available on the Internet over the past several years. Some of this information is inaccurate or misleading to patients. We attempted to determine the accuracy of information on the Internet concerning age-related macular degeneration (ARMD). The term "macular degeneration" was entered in each of seven Internet search engines, and the subsequent links were followed and categorized. The number of sites that discussed treatment inconsistent with the peer-reviewed standard of care for ARMD was tabulated. Of the 80 unique sites regarding ARMD that we identified, 17 (21%) featured nonconventional information. Many Internet sites feature unproven and costly nonconventional information about ARMD. Each physician should be prepared to address these sites and to suggest reliable sites concerning health information on the Internet.


Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.
Carnosine (β-alanyl-L-histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid-base balance, antioxidant properties, chelating agent, anti-crosslinking, and anti-glycation activities. High levels of carnosine and its analogue anserine (1-methyl carnosine) are found in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn-induced neuronal death. Here, the protective activity of carnosine against Zn-induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and Zn-induced gene expression were investigated using immortalised hypothalamic neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced neurotoxicity not by preventing increases in intracellular Zn(2+) but by participating in the regulation of the endoplasmic reticulum (ER) stress pathway and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and anserine protected against neurotoxicity induced by ER-stress inducers thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have future therapeutic potential for VD and other neurodegenerative diseases.


FUS regulates the alternative splicing of cell proliferation genes related to atherosclerosis.
FUS plays a significant role as an RNA-binding protein in several cellular processes, including RNA splicing, DNA repair, and transcriptional regulation. However, the RNA-binding capacity of FUS in atherosclerosis is unclear. We aimed to study the functions of FUS in inflammatory regulation through the role of the splicing factor. We knocked down FUS with siRNA to further study the overall transcriptional level and select alternative splicing (AS) of FUS regulation in human umbilical vein endothelial cells (HUVECs) by RNA sequencing. The results suggested that the knockdown of FUS significantly affected gene expression in HUVECs. In addition, the knockdown of FUS resulted in 200 differentially expressed genes (DEGs) that were highly related to apoptotic process, signal transduction, multicellular organism development, cell adhesion and regulation of transcription, and DNA-templated pathways. Importantly, FUS extensively regulated 2870 AS events with a significant difference. Functional analysis of its modulated AS genes revealed they were highly enriched in cell cycle and cell population proliferation pathways. The qRT-PCR and RNA-seq data showed consistent results. Our findings suggested new knowledge of the mechanisms of FUS associated with atherosclerosis.


Cooperative behaviour and phenotype plasticity evolve during melanoma progression.
A major challenge for managing melanoma is its tumour heterogeneity based on individual co-existing melanoma cell phenotypes. These phenotypes display variable responses to standard therapies, and they drive individual steps of melanoma progression; hence, understanding their behaviour is imperative. Melanoma phenotypes are defined by distinct transcriptional states, which relate to different melanocyte lineage development phases, ranging from a mesenchymal, neural crest-like to a proliferative, melanocytic phenotype. It is thought that adaptive phenotype plasticity based on transcriptional reprogramming drives melanoma progression, but at which stage individual phenotypes dominate and moreover, how they interact is poorly understood. We monitored melanocytic and mesenchymal phenotypes throughout melanoma progression and detected transcriptional reprogramming at different stages, with a gain in mesenchymal traits in circulating melanoma cells (CTCs) and proliferative features in metastatic tumours. Intriguingly, we found that distinct phenotype populations interact in a cooperative manner, which generates tumours of greater "fitness," supports CTCs and expands organotropic cues in metastases. Fibronectin, expressed in mesenchymal cells, acts as key player in cooperativity and promotes survival of melanocytic cells. Our data reveal an important role for inter-phenotype communications at various stages of disease progression, suggesting these communications could act as therapeutic target.


Renal Primitive Neuroectodermal Tumour: Case Report of a Rare Entity.
The peripheral Primitive Neuroectodermal Tumour (PNET) is a member of the family of small round cell tumours. PNET is more aggressive in kidney when compared to the other sites. It usually presents in childhood or adolescence. It has an aggressive clinical course and may process towards metastatic disease culminating in death. A 24-year-old female presented with left sided abdominal swelling. Abdominal ultrasound confirmed a heterogeneous left renal mass. Consequently the patient underwent nephrectomy of left kidney and left oophorectomy. Grossly, the tumour involved almost entire kidney, showed multi-lobular, grey, glistening appearance with focal haemorrhagic areas. Histologically, the tumour cells were arranged in diffuse infiltrating sheets, cohesive lobules, Homer-Wright rosettes and perivascular pseudo-rosettes. Individual tumour cells were small round cells with scant cytoplasm and round nuclei having dispersed chromatin. Features were suggestive of PNET. Immunohistochemistry showed tumour cells displaying strong membrane positivity for MIC 2. Renal PNET needs to be differentiated from other primary and metastatic renal round-cell tumours. Most of the cases of renal PNET have poor response to standard treatment of combined surgical resection, post-operative irradiation, and chemotherapy. PNET is a rare primary tumour in the kidney. Histopathological diagnosis has to be confirmed by immunophenotyping of the tumour cells.


Comparative performance of transcatheter aortic valve-in-valve implantation versus conventional surgical redo aortic valve replacement in patients with degenerated aortic valve bioprostheses: systematic review and meta-analysis.
The objective of this report was to directly compare, by means of a systematic review and meta-analysis, redo surgical aortic valve replacement (re-sAVR) with valve-in-valve transcatheter aortic valve implantation (ViV TAVI) for patients with failed degenerated aortic bioprostheses. Multiple databases were screened for all available reports comparing ViV TAVI with re-sAVR in patients with failing degenerated aortic bioprostheses. The primary outcome was all-cause mortality determined from the longest available survival data. Five observational studies (n = 342) were included in the meta-analysis; patients in the ViV TAVI group were older and had a higher baseline risk compared to those in the re-sAVR group. Although there was no statistical difference in procedural mortality [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.18-2.97; P = 0.67], 30-day mortality (RR 1.29, 95% CI 0.44-3.78; P = 0.64) and cardiovascular mortality (RR 0.91, 95% CI 0.30-2.70; P = 0.86) at a mean follow-up period of 18 months, cumulative survival analysis favoured surgery with borderline statistical significance (ViV TAVI versus re-sAVR: hazard ratio 1.91, 95% CI 1.03-3.57; P = 0.039). ViV TAVI was associated with a significantly lower rate of permanent pacemaker implantations (RR 0.37, 95% CI 0.20-0.68; P = 0.002) and shorter intensive care unit (P < 0.001) and hospital stays (P = 0.020). In contrast, re-sAVR offered superior echocardiographic outcomes: lower incidence of patient-prosthesis mismatch (P = 0.008), fewer paravalvular leaks (P = 0.023) and lower mean postoperative aortic valve gradients in the prespecified analysis (P = 0.017). The ViV TAVI approach is a safe and feasible alternative to re-sAVR that may offer an effective, less invasive treatment for patients with failed surgical aortic valve bioprostheses who are inoperable or at high risk. Re-sAVR should remain the standard of care, particularly in the low-risk population, because it offers superior haemodynamic outcomes with low mortality rates.


Numerical Study of Soft Colloidal Nanoparticles Interaction in Shear Flow.
The mechanical behavior of nanoparticle assemblies depends on complex particle interactions that are difficult to study experimentally. Depending on the nanoparticle morphology, these interactions could lead to adhesive and elastic-plastic behavior during contact deformation. The aim of this research is to study the effect of contact interactions between polymer nanoparticles and their impact on the macroscopic properties of formed aggregates. For this purpose, the discrete element method (DEM) was used to develop an interaction model combining elastic-plastic deformation and adhesion to study the behavior of spherical polymeric nanoparticles. Initially, a pair of particles interacting in the normal direction was simulated to evaluate the effect of adhesion and plastic deformation in the pull-off force of the contact. Based on these results, the simulations were extended to a dispersed system of nanoparticles, in which multibody interactions become dominant. Considering the aggregation between the nanoparticles induced by a shear flow, we performed an analysis of the number of aggregates and aggregates size in time to characterize the strength of clusters formed during the process. The simulation results showed that the interaction strength upon breakage of the clusters, correlating with the aggregates size, depends on the nanoparticle's softness. In this way, we verified that the type of contact interaction directly influences the macroscopic mechanical response of nanoparticle assemblies. Therefore, our model represents a new way of predicting the mechanical behavior of polymer nanoparticle systems and of optimizing it by adjusting primary particle properties.


Potential drugs and methods for preventing or delaying the progression of Huntington's disease.
Huntington's disease (HD) is an autosomal dominant inherited and progressive neurodegenerative disorder with motor dysfunction and cognitive deficits. Although there are no treatments to delay the appearance and the progression of HD, there are potential drugs currently in preclinical and clinical trials that are focused on HD therapy. The signaling pathways involved in HD are not yet clearly elucidated; however, expression of mutant huntingtin protein is considered a key factor in the induction and/or progression of HD. The demonstration that the onset and progression of HD in models of transgenic mice, in particular, are delayed or improved by the application of neurotrophic factors has emphasized their importance in neuroprotection in HD. In addition, other compounds targeting the HD gene or mutant huntingtin protein are currently in preclinical and clinical testing and may show promising neuroprotective effects. There are current patented drugs that are currently being considered as potential therapeutics for HD. These patented drugs may provide promising therapy for HD.


Hierarchical kernel mixture models for the prediction of AIDS disease progression using HIV structural gp120 profiles.
Changes to the glycosylation profile on HIV gp120 can influence viral pathogenesis and alter AIDS disease progression. The characterization of glycosylation differences at the sequence level is inadequate as the placement of carbohydrates is structurally complex. However, no structural framework is available to date for the study of HIV disease progression. In this study, we propose a novel machine-learning based framework for the prediction of AIDS disease progression in three stages (RP, SP, and LTNP) using the HIV structural gp120 profile. This new intelligent framework proves to be accurate and provides an important benchmark for predicting AIDS disease progression computationally. The model is trained using a novel HIV gp120 glycosylation structural profile to detect possible stages of AIDS disease progression for the target sequences of HIV+ individuals. The performance of the proposed model was compared to seven existing different machine-learning models on newly proposed gp120-Benchmark_1 dataset in terms of error-rate (MSE), accuracy (CCI), stability (STD), and complexity (TBM). The novel framework showed better predictive performance with 67.82% CCI, 30.21 MSE, 0.8 STD, and 2.62 TBM on the three stages of AIDS disease progression of 50 HIV+ individuals. This framework is an invaluable bioinformatics tool that will be useful to the clinical assessment of viral pathogenesis.


Exploring emotional contagion in zebrafish: A virtual-demonstrator study of positive and negative emotions.
Emotional contagion, the transmission of emotions within a group, has been extensively studied in mammals but remains largely unexplored in fish. This study aims to investigate whether emotional contagion, specifically in terms of low and high anxiety levels, can be evoked in zebrafish. This freshwater species has been gaining momentum due to its high genetic homology to humans and complex behavioral repertoire, making it well-suited for exploring social behavior. Our hypothesis posits that zebrafish have the ability to transmit positive and negative emotions to one another through visual cues only and that this transmission is robust over time. To test this, we employed a virtual demonstrator fish approach, where videos of zebrafish exhibiting either high or low geotactic behavior were shown to live zebrafish. Geotaxis, the tendency of a fish to spend more time at the bottom of the tank, is a sensitive measure of anxiety, with high geotactic behavior corresponding to high anxiety levels and vice versa. Our findings indicate that the virtual demonstrator successfully transmitted emotional states to the live fish, as evidenced by changes in the time spent at the bottom of the tank, linear acceleration, and fast-turning maneuvers, metrics that quantify anxiety-like behaviors such as geotaxis and erratic movements. Additionally, we conducted a causal analysis using a transfer entropy approach, revealing a significant flow of information from the virtual demonstrator fish to the live fish, indicating the efficacy and potential of this approach in studying emotional contagion. This study provides additional empirical evidence of how visual cues alone from a virtual demonstrator exhibiting high or low anxious behavior can elicit similar behavioral states in bystander fish, highlighting the potential for emotional contagion beyond mammalian and avian models.


Maternal diet, behaviour and offspring skeletal health.
Osteoporotic fracture has a major impact upon health, both in terms of acute and long term disability and economic cost. Peak bone mass, achieved in early adulthood, is a major determinant of osteoporosis risk in later life. Poor early growth predicts reduced bone mass, and so risk of fracture in later life. Maternal lifestyle, body build and 25(OH) vitamin D status predict offspring bone mass. Recent work has suggested epigenetic mechanisms as key to these observations. This review will explore the role of the early environment in determining later osteoporotic fracture risk.


Challenges and opportunities in evaluating programmes incorporating human-centred design: lessons learnt from the evaluation of Adolescents 360.
Adolescents 360 (A360) is a four-year initiative (2016-2020) to increase 15-19-year-old girls' use of modern contraception in Nigeria, Ethiopia and Tanzania. The innovative A360 approach is led by human-centred design (HCD), combined with social marketing, developmental neuroscience, public health, sociocultural anthropology and youth engagement 'lenses', and aims to create context-specific, youth-driven solutions that respond to the needs of adolescent girls. The A360 external evaluation includes a process evaluation, quasi-experimental outcome evaluation, and a cost-effectiveness study. We reflect on evaluation opportunities and challenges associated with measuring the application and impact of this novel HCD-led design approach. For the process evaluation, participant observations were key to capturing the depth of the fast-paced, highly-iterative HCD process, and to understand decision-making within the design process. The evaluation team had to be flexible and align closely with the work plan of the implementers. The HCD process meant that key information such as intervention components, settings, and eligible populations were unclear and changed over outcome evaluation and cost-effectiveness protocol development. This resulted in a more time-consuming and resource-intensive study design process. As much time and resources went into the creation of a new design approach, separating one-off "creation" costs versus those costs associated with actually implementing the programme was challenging. Opportunities included the potential to inform programmatic decision-making in real-time to ensure that interventions adequately met the contextualized needs in targeted areas. Robust evaluation of interventions designed using HCD, a promising and increasingly popular approach, is warranted yet challenging. Future HCD-based initiatives should consider a phased evaluation, focusing initially on programme theory refinement and process evaluation, and then, when the intervention program details are clearer, following with outcome evaluation and cost-effectiveness analysis. A phased approach would delay the availability of evaluation findings but would allow for a more appropriate and tailored evaluation design.


Marine endophytic fungi associated with Halopteris scoparia (Linnaeus) Sauvageau as producers of bioactive secondary metabolites with potential dermocosmetic application.
Marine fungi and, particularly, endophytic species have been recognised as one of the most prolific sources of structurally new and diverse bioactive secondary metabolites with multiple biotechnological applications. Despite the increasing number of bioprospecting studies, very few have already evaluated the cosmeceutical potential of marine fungal compounds. Thus, this study focused on a frequent seaweed in the Portuguese coast, Halopteris scoparia, to identify the endophytic marine fungi associated with this host, and assess their ability to biosynthesise secondary metabolites with antioxidative, enzymatic inhibitory (hyaluronidase, collagenase, elastase and tyrosinase), anti-inflammatory, photoprotective, and antimicrobial (Cutibacterium acnes, Staphylococcus epidermidis and Malassezia furfur) activities. The results revealed eight fungal taxa included in the Ascomycota, and in the most representative taxonomic classes in marine ecosystems (Eurotiomycetes, Sordariomycetes and Dothideomycetes). These fungi were reported for the first time in Portugal and in association with H. scoparia, as far as it is known. The screening analyses showed that most of these endophytic fungi were producers of compounds with relevant biological activities, though those biosynthesised by Penicillium sect. Exilicaulis and Aspergillus chevalieri proved to be the most promising ones for being further exploited by dermocosmetic industry. The chemical analysis of the crude extract from an isolate of A. chevalieri revealed the presence of two bioactive compounds, echinulin and neoechinulin A, which might explain the high antioxidant and UV photoprotective capacities exhibited by the extract. These noteworthy results emphasised the importance of screening the secondary metabolites produced by these marine endophytic fungal strains for other potential bioactivities, and the relevance of investing more efforts in understanding the ecology of halo/osmotolerant fungi.


Inflammatory biomarkers responses after acute whole body vibration in fibromyalgia.
The aims of this study were 1) to characterize the intensity of the vibration stimulation in women diagnosed with fibromyalgia (FM) compared to a control group of healthy women (HW) matched by age and anthropometric parameters, and 2) to investigate the effect of a single session of whole body vibration (WBV) on inflammatory responses. Levels of adipokines, soluble tumor necrosis factor receptors (sTNFr1, sTNFr2), and brain-derived neurotrophic factor (BDNF) were determined by enzyme-linked immunosorbent assay. Oxygen consumption (VO2) was estimated by a portable gas analysis system, heart rate (HR) was measured using a HR monitor, and perceived exertion (RPE) was evaluated using the Borg scale of perceived exertion. Acutely mild WBV increased VO2 and HR similarly in both groups. There was an interaction (disease vs vibration) in RPE (P=0.0078), showing a higher RPE in FM compared to HW at rest, which further increased in FM after acute WBV, whereas it remained unchanged in HW. In addition, there was an interaction (disease vs vibration) in plasma levels of adiponectin (P=0.0001), sTNFR1 (P=0.000001), sTNFR2 (P=0.0052), leptin (P=0.0007), resistin (P=0.0166), and BDNF (P=0.0179). In conclusion, a single acute session of mild and short WBV can improve the inflammatory status in patients with FM, reaching values close to those of matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced modulation towards greater adaptation to stress response in these patients.


Monitoring the temperature of dilute aqueous solutions using near-infrared water absorption.
An alternative spectroscopic approach for monitoring the temperature of aqueous solutions is presented. The method is based upon the temperature-induced spectral changes undergone by the second overtone (around 960 nm) of the near-infrared (NIR) water absorption band. Single and multilinear regression analysis are tested in order to evaluate the predictive ability of temperature. A linear dependence is found when measurements are performed at a single wavelength, but a lower prediction error is obtained when multilinear models are applied. No matrix effects produced by moderately concentrated common dissolved ions are found in a broad range of pH. A signal-to-noise ratio allows a precision of 0.5 degrees C for temperature monitoring. A prediction error of 0.77 degrees C (single linear regression) and 0.25 degrees C (multilinear approach) are achieved in a range from 15 to 90 degrees C. Advantages in terms of instrumentation and data analysis required are discussed.


Genetic pathways in the evolution of morphologically distinct colorectal neoplasms.
Colorectal adenomas can be morphologically classified as exophytic or flat. Polypoid cancers and cancers arising de novo (ie., without any adenomatous component) might be the results of genetic progression from exophytic and flat adenomas, respectively. In this study, we examined 94 morphologically distinct neoplastic specimens for mutations in K-RAS and analyzed 10 microsatellite loci tightly linked to the tumor suppressor genes APC, p53, DCC/SMAD4, hMSH2, and hMLH1. K-RAS mutations were significantly associated with exophytic adenomas [11 of 21 (52%)] compared to flat adenomas [2 of 13(15%), P < 0.03] and polypoid cancers [17 of 25 (68%)] compared to cancers arising de novo [7 of 25 (28%), P < 0.01]. Two polypoid cancer cases demonstrated three and four different K-RAS mutations, respectively, suggesting multiple areas of clonal expansion. Cancers arising de novo were significantly associated with loss of heterozygosity (LOH) at chromosome 3p compared to pol ypoid cancers [6 of 18(33%) versus 1 of 20(5%), P < 0.03], whereas the prevalence of LOH at chromosomes 2p, 5q, 17p, and 18q and microsatellite instability were not different between the groups. For all cancers, LOH at chromosomes 17p and 18q occurred in 47 and 51%, respectively. However, LOH at 17p and 18q occurred in 0 and 16% of benign lesions, respectively, suggesting their role in malignant transformation. There was no difference in LOH at chromosomes 17p and 18q between exophytic and flat lesions. These findings suggest that (a) mutant K-RAS is associated with the exophytic growth of colonic neoplasms, and that (b) some colorectal cancers arising de novo lose chromosome 3p during their evolution, which is not seen in polypoid cancers. Half of all cancers lose chromosomes 17p and 18q at or near the malignant transition of benign lesions as reported previously, irrespective of morphology. There may be more than one genetic avenue for colorectal cancer formation, and this correlates with the morphological characteristics.


HFOApp: A MATLAB Graphical User Interface for High-Frequency Oscillation Marking.
Epilepsy affects 3.4 million people in the United States, and, despite the availability of numerous antiepileptic drugs, 36% of patients have uncontrollable seizures, which severely impact quality of life. High-frequency oscillations (HFOs) are a potential biomarker of epileptogenic tissue that could be useful in surgical planning. As a result, research into the efficacy of HFOs as a clinical tool has increased over the last 2 decades. However, detection and identification of these transient rhythms in intracranial electroencephalographic recordings remain time-consuming and challenging. Although automated detection algorithms have been developed, their results are widely inconsistent, reducing reliability. Thus, manual marking of HFOs remains the gold standard, and manual review of automated results is required. However, manual marking and review are time consuming and can still produce variable results because of their subjective nature and the limitations in functionality of existing open-source software. Our goal was to develop a new software with broad application that improves on existing open-source HFO detection applications in usability, speed, and accuracy. Here, we present HFOApp: a free, open-source, easy-to-use MATLAB-based graphical user interface for HFO marking. This toolbox offers a high degree of intuitive and ergonomic usability and integrates interactive automation-assist options with manual marking, significantly reducing the time needed for review and manual marking of recordings, while increasing inter-rater reliability. The toolbox also features simultaneous multichannel detection and marking. HFOApp was designed as an easy-to-use toolbox for clinicians and researchers to quickly and accurately mark, quantify, and characterize HFOs within electrophysiological datasets.


Evaluation of DNA-protein complex structures using the deep learning method.
Biological processes such as transcription, repair, and regulation require interactions between DNA and proteins. To unravel their functions, it is imperative to determine the high-resolution structures of DNA-protein complexes. However, experimental methods for this purpose are costly and technically demanding. Consequently, there is an urgent need for computational techniques to identify the structures of DNA-protein complexes. Despite technological advancements, accurately identifying DNA-protein complexes through computational methods still poses a challenge. Our team has developed a cutting-edge deep-learning approach called DDPScore that assesses DNA-protein complex structures. DDPScore utilizes a 4D convolutional neural network to overcome limited training data. This approach effectively captures local and global features while comprehensively considering the conformational changes arising from the flexibility during the DNA-protein docking process. DDPScore consistently outperformed the available methods in comprehensive DNA-protein complex docking evaluations, even for the flexible docking challenges. DDPScore has a wide range of applications in predicting and designing structures of DNA-protein complexes.