Quality of Life and Perceived Social Support Before and After Sex Reassignment Surgery.
This study aimed to explore the pre- and postoperative differences in quality of life and perceived social support of Female-to-Male transsexual patients who underwent mastectomy and complete hysterectomy. Sixty-three Female-to-Male female individuals who underwent complete hysterectomy and mastectomy between November 2019 and November 2020 were included in this study. Data were collected using the Personal Information Form, Multidimensional Scale of Perceived Social Support, and the World Health Organization Quality of Life Scale Short Form. The pre- and postoperative perceived social support mean scores of patients were 57.2 ± 9.0 and 74.9 ± 7.3, respectively. The pre- and postoperative quality of life mean scores of patients were 76.9 ± 8.3 and 107.8 ± 10.1, respectively. There were statistically significant differences between the measurements (p < .05). In addition, the patients whose education level was primary school, whose income was less than their expenditure, whose father was a primary school graduate, whose family had a strict family opinion on sexuality, whose family had a traditional view, and who had a high body mass index were found to have higher postoperative social support perceptions and quality of life. The patients' postoperative quality of life and perceived social support improved after sex reassignment surgery.


Simultaneous Bayesian inference for skew-normal semiparametric nonlinear mixed-effects models with covariate measurement errors.
Longitudinal data arise frequently in medical studies and it is a common practice to analyze such complex data with nonlinear mixed-effects (NLME) models which enable us to account for between-subject and within-subject variations. To partially explain the variations, covariates are usually introduced to these models. Some covariates, however, may be often measured with substantial errors. It is often the case that model random error is assumed to be distributed normally, but the normality assumption may not always give robust and reliable results, particularly if the data exhibit skewness. Although there has been considerable interest in accommodating either skewness or covariate measurement error in the literature, there is relatively little work that considers both features simultaneously. In this article, our objectives are to address simultaneous impact of skewness and covariate measurement error by jointly modeling the response and covariate processes under a general framework of Bayesian semiparametric nonlinear mixed-effects models. The method is illustrated in an AIDS data example to compare potential models which have different distributional specifications. The findings from this study suggest that the models with a skew-normal distribution may provide more reasonable results if the data exhibit skewness and/or have measurement errors in covariates.


Real-world evaluation of second line chemotherapy for patients with advanced non-small cell lung cancer harboring preexisting interstitial lung disease.
The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD. The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed. Twenty-four patients with a median age of 71 years who were treated between April 2013 and March 2021 were included. The response rate after second-line chemotherapy with S-1 (n = 13), docetaxel (n = 8), pemetrexed (n = 2), or docetaxel plus ramucirumab (n = 1) was 12.5%, with a median progression-free survival (2nd line PFS) of 3.8 months. The overall survival from a start of first-line chemotherapy (1st line OS) and post-progression survival (PPS) post-first-line chemotherapy were 18.7 and 9.7 months, respectively. Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with 1st line OS (R = 0.85, P < 0.00001). Importantly, the 2nd line PFS was also significantly correlated with 1st line OS (R = 0.71, P = 0.0001). While second-line chemotherapy-related acute exacerbation of ILD was observed in 7 patients (29.2%), there were no treatment-related fatalities. Conslusions. Second-line chemotherapy has a strong positive impact on the OS of patients with NSCLC who have preexisting ILD. Given the findings of this study, second-line chemotherapy may be valuable in terms of prolonging long-term OS.


Dual-Phase Transmit Focusing for Multiangle Compound Shear-Wave Elasticity Imaging.
Shear-wave elasticity imaging (SWEI) enables the quantitative assessment of the mechanical properties of tissue. In SWEI, the effective generation of acoustic radiation force is of paramount importance. Consequently, several research groups have investigated various transmit beamforming and pulse-sequencing methods. To further improve the efficiency of the shear-wave generation, and therefore, to increase the quality of SWEI, we introduce a technique referred to as "multiangle compound SWEI" (MAC-SWEI), which uses simultaneous multiangular push beams created by dual-phase transmit focusing. By applying a constant phase offset on every other element of an array transducer, dual-phase transmit focusing creates both main and grating lobes (i.e., multiangular push beams for pushing) to simultaneously generate shear waves with several wavefront angles. The shear waves propagating at different angles are separated by multidirectional filtering in the frequency domain, leading to the reconstruction of multiple spatially co-registered shear-wave velocity maps. To form a single-elasticity image, these maps are combined, while regions associated with known artifacts created by the push beams are omitted. Overall, we developed and tested the MAC-SWEI method using Field II quantitative simulations and the experiments performed using a programmable ultrasound imaging system. Our results suggest that MAC-SWEI with dual-phase transmit focusing may improve the quality of elasticity maps.


Challenges and opportunities for engineered Escherichia coli as a pivotal chassis toward versatile tyrosine-derived chemicals production.
Growing concerns over limited fossil resources and associated environmental problems are motivating the development of sustainable processes for the production of high-volume fuels and high-value-added compounds. The shikimate pathway, an imperative pathway in most microorganisms, is branched with tyrosine as the rate-limiting step precursor of valuable aromatic substances. Such occurrence suggests the shikimate pathway as a promising route in developing microbial cell factories with multiple applications in the nutraceutical, pharmaceutical, and chemical industries. Therefore, an increasing number of studies have focused on this pathway to enable the biotechnological manufacture of pivotal and versatile aromatic products. With advances in genome databases and synthetic biology tools, genetically programmed Escherichia coli strains are gaining immense interest in the sustainable synthesis of chemicals. Engineered E. coli is expected to be the next bio-successor of fossil fuels and plants in commercial aromatics synthesis. This review summarizes successful and applicable genetic and metabolic engineering strategies to generate new chassis and engineer the iterative pathway of the tyrosine route in E. coli, thus addressing the opportunities and current challenges toward the realization of sustainable tyrosine-derived aromatics.


Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families.
Recent reports have demonstrated that mutations in the OPHN1 gene were responsible for a syndromic rather than non-specific mental retardation. Abnormalities of the posterior fossa with cerebellar hypoplasia have been demonstrated in all male patients reported to date. We report here a new family with X-linked mental retardation due to mutation in OPHN1 and present unpublished data about two families previously reported, concerning the facial and psychological phenotype of affected males and carrier females. Our study confirms that cerebellar hypoplasia is a hallmark of this syndrome. In addition, affected males display facial similarities that can help the diagnosis. Most carrier females have mild mental retardation and subtle facial changes.


Ethanol Extract of Capsella bursa-pastoris Improves Hepatic Steatosis Through Inhibition of Histone Acetyltransferase Activity.
Histone lysine acetylation is thought to play a role in regulating the balance between energy storage and energy expenditure. However, the epigenetic mechanisms by which food phytochemicals influence metabolic processes in the liver have not been thoroughly investigated. In this study, we investigated the effect of an ethanol extract of Capsella bursa-pastoris (ECB) on histone acetyltransferase (HAT) inhibition, and whether it could thereby attenuate lipid accumulation in vitro and in vivo. We observed that ECB inhibits HAT activity as assessed by colorimetric and autoradiography assay systems. ECB also reduced oleic acid (OA)-stimulated histone acetylation at H4K5 and H4K12 and attenuated OA-mediated lipid accumulation in HepG2 cells, in the absence of observable cytotoxicity. We then investigated these effects in vivo. Mice were fed on either a normal diet (ND) or high-fat diet (HFD) in the presence or absence of ECB supplementation. In comparison with the ND controls, the HFD mice exhibited higher body weight, liver fat, adipose tissue size, and total serum cholesterol concentrations, and these effects were significantly attenuated by ECB supplementation. Taken together, these results suggest that ECB protects against the mechanisms responsible for HFD-induced hepatic steatosis, and may involve the targeting of histone H4K acetylation.


Depo-Provera does not alter disease progression in SIVmac-infected female Chinese rhesus macaques.
Depo-Provera (medroxyprogesterone acetate), a long-acting derivative of progesterone, is utilized during many nonhuman primate microbicide studies to facilitate simian immunodeficiency virus (SIV) infection by thinning the vaginal epithelium. To date, the systemic effects of this steroid hormone in regard to SIV/HIV pathogenesis are not well understood, but an increase in infection rates and lymphoproliferation following progesterone application has been reported. Therefore, a proactive study using 20 Chinese rhesus macaques was designed to investigate the effect of a single Depo-Provera injection on SIV disease progression. Group 1 (n = 10) was treated with 30 mg Depo-Provera intramuscularly 30 days prior to intravenous challenge with 50 TCID(50) SIVmac251, while Group 2 (n = 10) remained untreated, but received the same amount of SIV. Blood samples were taken at predetermined intervals to measure RNA viral loads, CD4(+), CD8(+), and CD20(+) lymphocyte counts and percentages and absolute numbers of naive and memory T lymphocytes. Upon statistical endpoint data analysis, none of the parameters measured were shown to be significantly different between the groups. One animal in the Depo-Provera-treated group and two macaques in the control group were euthanized prior to study end due to the development of clinical signs (in weeks 43 and 51, respectively). All other animals were euthanized between weeks 68 and 71 post-SIV infection. Histopathological evaluations revealed that 5 of 10 animals in each group had developed simian AIDS (SAIDS). In summary, this prospective study demonstrated that a single injection of 30 mg Depo-Provera did not have a significant influence on SIV disease progression.


Recommendations for the implantation of the Pericarbon Freedom stentless valve.
Based on our experience of 1000 subcoronary implants of the Sorin Pericarbon Freedom stentless valve, we give recommendations for the exact implantation technique. This article illustrates basic issues in the implantation technique with respect to continuous and interrupted suture to enable beginners and experienced surgeons to avoid some of the pitfalls. Additional remarks about sizing and early intraoperative echocardiographic findings complete this technical overview.


Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion.
Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol.


Production of Flavonoid 7-O-glucosides by Bioconversion Using Escherichia coli Expressing a 7-O-glucosyltransferase from Tobacco (Nicotiana tabacum).
Flavonoid 7-O-glucosides exhibit various biological activities; however, some are not abundant in nature. Therefore, a method to produce flavonoid 7-O-glucosides was investigated. Escherichia coli expressing tobacco-derived glucosyltransferase (Ec-NtGT2) converted several flavonoids (apigenin, luteolin, quercetin, kaempferol, and naringenin) to their 7-O-glucosides with conversion rates of 67-98%. In scaled-up production, Ec-NtGT2 yielded 24 mg/L of apigenin 7-O-glucoside, 41 mg/L of luteolin 7-O-glucoside, 118 mg/L of quercetin 7-O-glucoside, 40 mg/L of kaempferol 7-O-glucoside, and 75 mg/L of naringenin 7-O-glucoside through sequential administration of substrates in 4-9 h. The conversion rates of apigenin, luteolin, quercetin, kaempferol, and naringenin were 97%, 72%, 77%, 98%, and 96%, respectively. These results indicated that Ec-NtGT2 is a simple and efficient bioconversion system for the production of flavonoid 7-O-glucosides.


Safety of Triage Self-assessment Using a Symptom Assessment App for Walk-in Patients in the Emergency Care Setting: Observational Prospective Cross-sectional Study.
Increasing use of emergency departments (EDs) by patients with low urgency, combined with limited availability of medical staff, results in extended waiting times and delayed care. Technological approaches could possibly increase efficiency by providing urgency advice and symptom assessments. The purpose of this study is to evaluate the safety of urgency advice provided by a symptom assessment app, Ada, in an ED. The study was conducted at the interdisciplinary ED of Marburg University Hospital, with data collection performed between August 2019 and March 2020. This study had a single-center cross-sectional prospective observational design and included 378 patients. The app's urgency recommendation was compared with an established triage concept (Manchester Triage System [MTS]), including patients from the lower 3 MTS categories only. For all patients who were undertriaged, an expert physician panel assessed the case to detect potential avoidable hazardous situations (AHSs). Of 378 participants, 344 (91%) were triaged the same or more conservatively and 34 (8.9%) were undertriaged by the app. Of the 378 patients, 14 (3.7%) had received safe advice determined by the expert panel and 20 (5.3%) were considered to be potential AHS. Therefore, the assessment could be considered safe in 94.7% (358/378) of the patients when compared with the MTS assessment. From the 3 lowest MTS categories, 43.4% (164/378) of patients were not considered as emergency cases by the app, but could have been safely treated by a general practitioner or would not have required a physician consultation at all. The app provided urgency advice after patient self-triage that has a high rate of safety, a rate of undertriage, and a rate of triage with potential to be an AHS, equivalent to telephone triage by health care professionals while still being more conservative than direct ED triage. A large proportion of patients in the ED were not considered as emergency cases, which could possibly relieve ED burden if used at home. Further research should be conducted in the at-home setting to evaluate this hypothesis. German Clinical Trial Registration DRKS00024909; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00024909.


Wireless Addressable Cortical Microstimulators Powered by Near-Infrared Harvesting.
Ensembles of autonomous, spatially distributed wireless stimulators can offer a versatile approach to patterned microstimulation of biological circuits such as the cortex. Here, we demonstrate the concept of a distributed, untethered, and addressable microstimulator, integrating an ultraminiaturized ASIC with a custom-designed GaAs photovoltaic (PV) microscale energy harvester, dubbed as an "optical neurograin (ONG)". An on-board Manchester-encoded near-infrared downlink delivers incident IR power and provides a synchronous clock across an ensemble of microdevices, triggering stimulus events by remote command. Each ONG has a unique device address and, when an incoming downlink bit sequence matches with this device identification (ID), the implant delivers a charge-balanced current stimulus to the target cortex. Present devices use 7-bit metal fuses fabricated during the CMOS process for their device ID, laser-scribed in post-processing, allowing in principle for a stimulator network of up to 128 nodes. We have characterized small ensembles of ONGs and shown a proof of concept of the system both on benchtop and in vivo rat rodent model.


Ixodes ricinus and Its Transmitted Pathogens in Urban and Peri-Urban Areas in Europe: New Hazards and Relevance for Public Health.
Tick-borne diseases represent major public and animal health issues worldwide. Ixodes ricinus, primarily associated with deciduous and mixed forests, is the principal vector of causative agents of viral, bacterial, and protozoan zoonotic diseases in Europe. Recently, abundant tick populations have been observed in European urban green areas, which are of public health relevance due to the exposure of humans and domesticated animals to potentially infected ticks. In urban habitats, small and medium-sized mammals, birds, companion animals (dogs and cats), and larger mammals (roe deer and wild boar) play a role in maintenance of tick populations and as reservoirs of tick-borne pathogens. Presence of ticks infected with tick-borne encephalitis virus and high prevalence of ticks infected with Borrelia burgdorferi s.l., causing Lyme borreliosis, have been reported from urbanized areas in Europe. Emerging pathogens, including bacteria of the order Rickettsiales (Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis," Rickettsia helvetica, and R. monacensis), Borrelia miyamotoi, and protozoans (Babesia divergens, B. venatorum, and B. microti) have also been detected in urban tick populations. Understanding the ecology of ticks and their associations with hosts in a European urbanized environment is crucial to quantify parameters necessary for risk pre-assessment and identification of public health strategies for control and prevention of tick-borne diseases.


Development of an immunochromatographic strip for antibody detection of pseudorabies virus in swine.
An immunochromatographic strip was developed for the serological detection of pseudorabies virus (PRV) in swine. In the strip, the expressed protein of gB, one of the glycoproteins of PRV, labeled with colloidal gold, was used as the detector; staphylococcal protein A and swine anti-pseudorabies virus antibody were blotted on nitrocellulose membrane for the test and control lines, respectively. The specificity of the strip was 98.1%, and the sensitivity of the strip with reference anti-PRV serum was 96.0%. Swine serum samples (296) were collected to evaluate the characteristics of the strip in comparison with an existing commercial kit. The agreement was 93.6%. Furthermore, the dipstick assay based on the strip is rapid (5 min) and easy to perform with no requirement of professional skills, reagents, or equipment. This suggests that the immunochromatographic strip is an acceptable alternative for use in clinical laboratories lacking specialized equipment and for field diagnosis.


The third era of human rights: global accountability.
This article argues that the trend in the current protection of human rights may be seen as a revival of an old idea: governments are accountable for their actions. The protection of human rights has gone through three eras. In the first era, the Catholic Church in the Middle Ages claimed to rule from a divine mandate. This principle of natural law was a unifying factor in western Europe because it created a standard system of morality. The second era, beginning in the seventeenth century with the doctrine of state sovereignty, rejected that natural law. Rulers wanted to run their own territories and not be subject to foreign influence. Laws were created by the 'national sovereign' (king, queen, president, parliament, congress and so on). This legal doctrine survived for about three centuries, but the excesses of leaders such as Hitler in the middle of last century forced a re-think. Although the term 'natural law' is not used, there has been a revival of its essential meaning: that governments have to be answerable to a higher authority for their behaviour.


Improving the safety and efficacy of phage therapy from the perspective of phage-mammal interactions.
Phage therapy has re-emerged as a promising solution for combating antimicrobial-resistant bacterial infections. Increasingly, studies have revealed that phages possess therapeutic potential beyond their antimicrobial properties, including regulating the gut microbiome and maintain intestinal homeostasis, as a novel nanocarrier for targeted drug delivery. However, the complexity and unpredictability of phage behavior during treatment pose a significant challenge in clinical practice. The intricate interactions established between phages, humans, and bacteria throughout their long coexistence in the natural ecosystem contribute to the complexity of phage behavior in therapy, raising concerns about their efficacy and safety as therapeutic agents. Revealing the mechanisms by which phages interact with the human body will provide a theoretical basis for increased application of promising phage therapy. In this review, we provide a comprehensive summary of phage-mammal interactions, including signaling pathways, adaptive immunity responses, and phage-mediated anti-inflammatory responses. Then, from the perspective of phage-mammalian immune system interactions, we present the first systematic overview of the factors affecting phage therapy, such as the mode of administration, the physiological status of the patient, and the biological properties of the phage, to offer new insights into phage therapy for various human diseases.


Enzyme-linked immunosorbent assay for quantification of rabies antibodies in human sera.
A double antibody enzyme linked immunosorbent assay (ELISA) was elaborated for detection of rabies antibodies in human sera. The procedure consisted of coating polyvinylchloride plates with rabbit antirabies serum followed by attachment of partially purified fixed virus and human rabies antibodies. The rabies-specific antibodies in human antisera were quantified by means of antihuman peroxidase conjugate. Titration of antisera from human volunteers immunized with the "Fermi" vaccine revealed excellent correlation of the virus neutralization test and ELISA.


Polymyxin B versus colistin: an update.
Polymyxin B and colistin (polymyxin E) are polypeptide antibiotics that were developed in the 1940s, but fell into disfavor due to their high toxicity rates. These two antibiotics were previously regarded to be largely equivalent, due to similarities in their chemical structure and spectrum of activity. In recent years, several pertinent differences, especially in terms of potency and disposition, have been revealed between polymyxin B and colistin. These differences are mainly attributed to the fact that polymyxin B is administered parenterally in its active form, while colistin is administered parenterally as an inactive pro-drug, colistimethate. In this review, we summarize the similarities and differences between polymyxin B and colistin. We also discuss the potential clinical implications of these findings, and provide our perspectives on how polymyxins should be employed to preserve their utility in this era of multi-drug resistance.


Optical ac coupling to overcome limitations in the detection of optical power fluctuations.
A high-sensitivity detection method for optical power fluctuations is demonstrated based on photodetection in reflection of an optical resonator with a specific impedance matching. That resonator is used to reduce the carrier power reflected by the resonator while preserving the power fluctuation sidebands for frequencies above the resonator bandwidth. A sensitivity of 7 x 10(-10) Hz(-1/2) for relative power fluctuations was achieved with only 3 mA of detected photocurrent and 99.6% of the power remained for downstream experiments. As in the widely used ac coupling of electrical signals, this technique overcomes dynamic-range limits and reduces detector noise associated with large carrier amplitudes of the optical field.


Sun leaves up-regulate the photorespiratory pathway to maintain a high rate of CO2 assimilation in tobacco.
The greater rate of CO2 assimilation (A n) in sun-grown tobacco leaves leads to lower intercellular and chloroplast CO2 concentrations and, thus, a higher rate of oxygenation of ribulose-1,5-bisphosphate (RuBP) than in shade-grown leaves. Impairment of the photorespiratory pathway suppresses photosynthetic CO2 assimilation. Here, we hypothesized that sun leaves can up-regulate photorespiratory pathway to enhance the A n in tobacco. To test this hypothesis, we examined the responses of photosynthetic electron flow (J T) and CO2 assimilation to incident light intensity and intercellular CO2 concentration (C i) in leaves of 'k326' tobacco plants grown at 95% sunlight (sun plants) or 28% sunlight (shade plants). The sun leaves had higher photosynthetic capacity and electron flow devoted to RuBP carboxylation (J C) than the shade leaves. When exposed to high light, the higher Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) content and lower C i in the sun leaves led to greater electron flow devoted to RuBP oxygenation (J O). The J O/J C ratio was significantly higher in the sun leaves than in the shade leaves under strong illumination. As estimated from CO2-response curves, the maximum J O was linearly correlated with the estimated Rubisco content. Based on light-response curves, the light-saturated J O was linearly correlated with light-saturated J T and light-saturated photosynthesis. These findings indicate that enhancement of the photorespiratory pathway is an important strategy by which sun plants maintain a high A n.


Graphene-Dendrimer Nanostars for Targeted Macrophage Overexpression of Metalloproteinase 9 and Hepatic Fibrosis Precision Therapy.
Fibrosis contributes to ∼45% of all deaths in industrialized nations, but no direct antifibrotic therapeutic interventions exist to date. Graphene-based nanomaterials exhibit excellent versatility in electronics, and emerging trends exploit their properties for biomedical applications, especially for drug and gene delivery. We designed constructs of graphene nanostars linked to PAMAM-G5 dendrimer for the selective targeting and delivery of a plasmid expressing the collagenase metalloproteinase 9 under the CD11b promoter into inflammatory macrophages in cirrhotic livers. Graphene nanostars preferentially accumulated in inflammatory macrophages M1 in less than 3 h in a manner unaffected by covalent linkage to dendrimers. Dendrimer-graphene nanostars efficiently delivered the plasmid encoding for metalloproteinase 9 into macrophages, allowing the synthesis and secretion of the metalloproteinase to digest adjacent collagen fibers. In turn, metalloproteinase 9 overexpression promoted the macrophage switch from inflammatory M1 to pro-regenerative M2 in 3 days. This targeted gene therapy reduced selectively and locally the presence of collagen fibers in fibrotic tracts where inflammatory macrophages accumulated in cirrhotic mice without affecting the activation state of hepatic stellate cells. Overall, this treatment significantly reduced hepatic injury and improved liver restoration in mice with liver cirrhosis treated for 10 days. Graphene-dendrimer nanostars targeted the macrophage overexpression of metalloproteinase 9, selectively reducing hepatic fibrosis, and might be a good treatment for diseases associated with fibrosis and inflammatory macrophage accumulation.


Substance P and cholecystokinin-like peptides in Helix neurons and cholecystokinin and serotonin in a giant neuron.
Immunohistochemical procedures revealed that the serotonin-containing cell situated in each metacerebral ganglion of the snail Helix also contains a cholecystokinin-like peptide, but is devoid of substance P. In radioimmunoassays the cholecystokinin-like material showed similarities to the carboxy terminal regions of mammalian cholecystokinin and gastrin. Since much is known about the morphology and synaptic connections of this serotonin neuron, the role of the cholecystokinin-like peptides can now be investigated by neurophysiological methods, thus opening the way to discovering whether a neuron can use more than one transmitter.


Substance P increases catecholamine secretion from perfused rat adrenal glands evoked by prolonged field stimulation.
1. We have studied the effect of substance P (SP) on catecholamine (CA) secretion evoked by prolonged field stimulation from the perfused rat adrenal gland in vitro. 2. Previous studies show that SP has an inhibitory effect on the nicotinic response in a number of different tissue preparations. In the present study, we found that SP at concentrations from 10(-7) to 10(-6) M markedly increased CA secretion evoked by prolonged high-frequency field stimulation but not that evoked by low-frequency field stimulation. 3. In the absence of field stimulation SP by itself had no direct effect on CA secretion. This indicates that SP acts as a neuromodulator rather than a neurotransmitter to increase CA secretion from the adrenal medulla. 4. The nicotinic receptors were still functional following a period of prolonged field stimulation (120 min) because CA secretion was markedly increased in response to the nicotinic agonist dimethylphenylpiperazinium (DMPP). 5. Capsaicin pre-treatment reduced CA secretion evoked by prolonged field stimulation and the facilitatory action of SP on CA secretion lasted longer in these capsaicin-pre-treated rats than in controls, indicating that SP-containing capsaicin-sensitive fibres innervating the adrenal medulla may be involved in the regulation of CA secretion. 6. In parallel with the increase in CA secretion, 3H overflow from the splanchnic nerve pre-labelled with [3H]choline was also increased by SP. The increase in CA secretion by SP lasted longer than the increase in 3H overflow. These results suggest that SP facilitates CA secretion from the adrenal gland at two levels: (1) pre-synaptically by facilitating ACh release from splanchnic nerve terminals, and (2) post-synaptically by modulating the nicotinic secretory response by protection against nicotinic desensitization of secretion. 7. The present studies provide further evidence that endogenous SP in the splanchnic nerve may modulate CA secretion during stress.


Public health preparedness and response capacity inventory validity study.
The Centers for Disease Control and Prevention's Public Health Practice Program Office has issued a Public Health Preparedness and Response Capacity Inventory to help state and local public health systems assess their progress towards achievement of the critical capacities and benchmarks specified in the federal Supplemental Funds for Public Health Preparedness and Response for Bioterrorism. The criterion validity of the capacity inventory was assessed by comparing selected state and local agency responses with documentation provided by the agencies to corroborate their answers. Content validity assessment took the form of a mailed survey that also identified the most important questions from the perspective of a separate set of state and local officials. Responses generally upheld the validity of the capacity inventory, although circumstantial threats to validity were identified in the testing process. The instrument's use has been reported to the Centers for Disease Control and Prevention by approximately half the states and over 800 local public health entities. An interactive electronic version includes a scoring mechanism that allows agencies to judge progress towards the critical capacities and benchmarks over time.


Olive, soybean and palm oils intake have a similar acute detrimental effect over the endothelial function in healthy young subjects.
Currently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function. To evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function. Ten healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60 mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0-36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5-33.3), independently of the type of oil ingested (p=0.44) and regardless of its deep-fry level (p=0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment (r=-0.22, p=0.09). No difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.


Detection of qacΔE Efflux Pump Gene among the Clinical Isolates of Escherichia coli and its Correlation with Resistance to Disinfectants.
Disinfectants and antiseptics inhibit the dissemination of pathogenic organisms in hospitals but often cause disinfectant-resistant microorganisms, an important factor for nosocomial infection. This study aimed to evaluate the correlation between qacΔE efflux pump gene and its resistance to disinfectants among Escherichia coli clinical isolates. A total of 97 E. coli isolates were isolated from patients with urinary tract infections. The minimum inhibition concentration (MIC) value of chlorhexidine and benzalkonium chloride was determined using broth microdilution method. Effect of efflux pumps was assessed by MIC test in the presence of phenylalanine-arginine β-naphthylamide (PAβN), and then the qacΔE efflux pump gene was detected using polymerase chain reaction (PCR). Of the isolates, 85.6% and 61.9% were resistant to chlorhexidine and benzalkonium chloride, respectively. Following the treatment of isolates with the efflux pump's inhibitor, PAβN, the MIC value of chlorhexidine and benzalkonium chloride decreased in 75.2% and 57.7% of the isolates, respectively. A significant correlation was found between PAβN treatment and the change in the resistant strains to susceptible strains (p = 0.021). The qacΔE gene was detected in 84.5% (n = 82) of the isolates, and the presence of the gene amongst disinfectant-resistant strains was also significant (p < 0.001). It is suggested to conduct other studies on other efflux pumps, as well as to periodically monitor the resistance to disinfectants. Substances inhibiting efflux pumps and neutral compounds are effective in the reduction of resistance to disinfectants. New disinfectants and drugs should be designed.


Effects of Exercise Intervention on Habitual Physical Activity Above Lactate Threshold Under Free-living Conditions: A Randomized Controlled Trial.
The purpose of the present investigation was to examine the effects of an exercise-based intervention on the daily physical activity (PA) above the lactate threshold under free-living conditions. A total of 81 middle-aged to older males (51±7 years) were randomly assigned into one of 2 groups. The subjects' body weight, visceral fat area, lactate threshold (LT), and PA levels were measured before and after the 8-week lifestyle intervention. The PA levels were assessed using a pedometer with a uni-axial accelerometer (Lifecorder, Kenz, Nagoya). During the intervention, 300 min/week of exercise at LT was targeted in the exercise group. The LT was determined by the log-log transformation method. The subjects in the control group were instructed to maintain their usual lifestyles. In the exercise group, the body weight, visceral fat area and LT significantly improved after the intervention. In contrast, the duration of PA at an intensity of LT, >3 METs and >6 METs did not differ significantly. The present investigation did not find significant changes in the PA at LT under free-living conditions as a result of an 8-week exercise-based intervention, although the participants successfully improved their aerobic capacity and body composition.


Exocytosis in mammalian cells. VI. Temperature dependence of pancreatic exocrine secretion.
The effects of temperature on amylase secretion in vitro have been measured under stimulated and nonstimulated conditions. In both cases a very rapid decrease of secretory rate was observed between 37 and 25 degrees C (60-70%). The decrease is less pronounced between 25 an 15 degrees C. Between 15 and 13 degrees C a drop of secretory activity (10%) was observed under stimulation whereas an increase was measured in absence of stimulus. At lower temperatures the rate of secretion falls again abruptly. These results show that the secretory pattern of amylase from pancreas in vitro as a function of temperature is very different under stimulated and nonstimulated conditions. We suggest that the abrupt change of secretory activity between 15 and 13 degrees C could correspond to a change of physical state of the membranes involved in the exocytosis process.


Determination of ferulic acid by flow injection chemiluminescence analysis based on enhancement of the N-bromobutanimide-eosin-CrCl3 system in alkaline solution.
A simple and sensitive flow injection chemiluminescence method has been developed for the determination of ferulic acid (FA) based on the significant enhancement effect of FA on the CL signal of the N-bromobutanimide (NBS)-eosin-CrCl3 system in alkaline solution. Under optimum conditions, the enhanced CL intensity is linearly related to the concentration of FA in its pharmaceutical preparations and human plasma samples. The corresponding linear regression equations were established over the 4.0 × 10(-10)-1.0 × 10(-7) g/mL for FA tablets and 2.0 × 10(-10)-1.0 × 10(-7) g/mL for plasma samples. The limit of detection for FA tablets and limit of quantification for plasma samples were 2.8 × 10(-10) g/mL (3 σ) and 3.04 × 10(-10) g/mL (10 σ), respectively. A complete analysis could be performed within 40 s, including washing and sampling, giving a throughput of ≈90/h. The proposed method was successfully applied to the determination of FA in pharmaceutical preparations and human plasma samples with satisfactory results. The recoveries of pharmaceutical preparations and human plasma samples at three different concentrations were 97.8-102.6% and 96.7-104.0%, respectively. Furthermore, the possible mechanism of CL reactions was also discussed briefly.


Glass ionomer cements used as fissure sealants with the atraumatic restorative treatment (ART) approach: review of literature.
To review the success of newer, more-viscous aesthetic conventional glass ionomer cements (GICs), that have been marketed specifically for the atraumatic restorative (ART) technique or approach, when used as pit and fissure sealants. As part of this approach, enamel fissures adjacent to the ART restorations are conditioned with poly (acrylic) acid (PAA) and then usually sealed with a GIC, using the finger-press method. The newer GICs appear in vitro to penetrate adequately and seal occlusal fissures in permanent molar teeth, and clinical studies of the ART approach over three years have found sealant retention (full and partial) to be approximately 70%, with fissure caries approximately 0-4%. In two studies, fissure caries was significantly reduced in sealed as compared with unsealed teeth over three years. Although the results appear to be better with the newer than with earlier conventional GIC products, the ART studies have generally involved populations at low-risk to caries, and further improvements in the mechanical properties of the cements are required for optimal long-term clinical success. Etching the enamel fissures with phosphoric acid, instead of conditioning with PAA, before GIC sealant placement warrants clinical investigation.


Response to dietary wheat bran in the exocrine pancreas and intestine of rats.
Rats were fed a fiber-free (FF) mixture or the same diet with a supplement of 20% wheat bran (WB). After 2 weeks, the pancreas contained higher levels of amylase and trypsin in rats fed WB. In response to a meal, the intestine contained more lipase activity in the WB group. The dry weight of material and protein level in the intestinal contents were also elevated in the WB group. The size of the intestinal villi had not changed, but it did contain more goblet cells. The results indicate that consumption of wheat bran can lead to changes in the exocrine pancreas, perhaps associated with shifts in gut hormones, and may effect absorption by increasing the bulk of material as well as enhancing mucus production in the intestine.


Can Music Foster Learning - Effects of Different Text Modalities on Learning and Information Retrieval.
This study investigates the possibilities of fostering learning based on differences in recall and comprehension after learning with texts which were presented in one of three modalities: either in a spoken, written, or sung version. All three texts differ regarding their processing, especially when considering working memory. Overall, we assume the best recall performance after learning with the written text and the best comprehension performance after learning with the sung text, respectively, compared to both other text modalities. We also analyzed whether the melody of the sung material functions as a mnemonic aid for the learners in the sung text condition. If melody and text of the sung version are closely linked, presentation of the melody during the post-test phase could foster text retrieval. 108 students either learned from a sung text performed by a professional singer, a printed text, or the same text read out loud. Half of the participants worked on the post-test while listening to the melody used for the musical learning material and the other half did not listen to a melody. The written learning modality led to significantly better recall than with the spoken (d = 0.97) or sung text (d = 0.78). However, comprehension after learning with the sung modality was significantly superior compared to when learning with the written learning modality (d = 0.40). Reading leads to more focus on details, which is required to answer recall questions, while listening fosters a general understanding of the text, leading to higher levels of comprehension. Listening to the melody during the post-test phase negatively affected comprehension, irrespective of the modality during the learning phase. This can be explained by the seductive detail effect, as listening to the melody during the post-test phase may distract learners from their main task. In closing, theoretical and practical implications are discussed.


Effects of thiopental, ketamine, diazepam, xylazine, and nitrous oxide on EEG spike activity and convulsive behavior during enflurane anesthesia in atropinized cats. Effect of increasing inhalant concentrations.
The effects of thiopental, ketamine, diazepam, xylazine, and nitrous oxide, and the combinations of thiopental-nitrous oxide and ketamine-nitrous oxide, on both enflurane-induced electroencephalographic (EEG) spike activity and convulsive behavior were measured quantitatively in atropinized cats receiving enflurane with controlled ventilation. Pretreatments with thiopental, ketamine, and diazepam reduced both EEG spike frequency and amplitude at 2.5% to 4.5% inspired enflurane but did not abolish spike activity. Nitrous oxide (66% of inspired gas) did not significantly alter spike frequency or amplitude during 2.5% to 4.5% inspired enflurane, but the combination of thiopental-nitrous oxide or ketamine-nitrous oxide reduced EEG spike activity during 2.5% inspired enflurane. Enflurane-induced convulsive score was markedly suppressed by thiopental and ketamine and was significantly reduced by diazepam, xylazine and nitrous oxide. The combinations of thiopental-nitrous oxide and ketamine-nitrous oxide greatly reduced behavioral-convulsive responses induced by 2.5% to 4.5% inspired enflurane.


[Lean, work and psychological well-being.]
Many studies have confirmed the existence of a close relationship between job satisfaction and health. The Siena University Hospital introduced the Lean approach to support personnel development/empowerment and promote a constant improvement in work organization, with the aim of creating value for patients, professionals and the whole organization. The purpose of this study was to examine whether the introduction and the development of this improvement approach in healthcare could contribute to the enhancement of psychological wellbeing and employee satisfaction, with a positive value in preventing related stress work. The Lyne and Barrett Employee Wellbeing Questionnaire (EWQ) was administered to employees involved in selected Lean projects carried out at the Siena University Hospital. The EWQ is composed of 59 items and it is structured in three areas: organizational wellbeing, working satisfaction and workload. The analysis of the results showed significant evidence of the impact of improvement activities on the working satisfaction and the workload.


Solution-processable singlet fission photovoltaic devices.
We demonstrate the successful incorporation of a solution-processable singlet fission material, 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene), into photovoltaic devices. TIPS-pentacene rapidly converts high-energy singlet excitons into pairs of triplet excitons via singlet fission, potentially doubling the photocurrent from high-energy photons. Low-energy photons are captured by small-bandgap electron-accepting lead chalcogenide nanocrystals. This is the first solution-processable singlet fission system that performs with substantial efficiency with maximum power conversion efficiencies exceeding 4.8%, and external quantum efficiencies of up to 60% in the TIPS-pentacene absorption range. With PbSe nanocrystal of suitable bandgap, its internal quantum efficiency reaches 170 ± 30%.


Aromatic amino acid decarboxylase (AADC) immunohistochemistry in vertebrate brainstem with an antiserum raised against AADC made in E. coli.
Aromatic L-amino acid decarboxylase (AADC) is involved in the biosynthesis of catecholamines and indolamines. AADC is present in the nervous system, in the chromaffin cells, and in non-neuronal tissues. We tested the capacity of a new polyclonal antibody, obtained by immunization of rabbits with a recombinant protein beta-galactosidase-AADC, to detect monoaminergic neurons in the brainstem as well as monoaminergic paraneurons in the adrenal medulla from goldfish, frog, skink, quail, and mouse. In the adrenal gland we found an immunoreactivity that was consistent with the distributions of the chromaffin cells previously reported. In the brainstem, groups of immunoreactive neurons and several labelled fibers were observed in the five species studied. The raphe region showed cell bodies and processes similar to those previously identified as monoaminergic by other authors. In addition, in medulla oblongata and isthmic tegmentum we found, in goldfish, skink, and quail, neuronal groups similar to mammalian D groups which contain AADC but are devoided of serotonin and catecholamines.


Non-Mendelian transmission in a human developmental disorder: split hand/split foot.
The study of Mendelian disorders that do not meet some Mendelian expectations has led to an increased understanding of such previously obscure genetic phenomena as anticipation. Split hand/split foot (SHSF), a human developmental malformation, demonstrates such distinctive genetic features as reduced penetrance and variable expressivity. In this study, new pedigrees with defined ascertainment confirm the existence of non-Mendelian transmission characterized by the overtransmission of SHSF from affected fathers to sons.


Plastic fiber scintillator response to fast neutrons.
The Neutron Imaging System at NIF uses an array of plastic scintillator fibers in conjunction with a time-gated imaging system to form an image of the neutron emission from the imploded capsule. By gating on neutrons that have scattered from the 14.1 MeV DT energy to lower energy ranges, an image of the dense, cold fuel around the hotspot is also obtained. An unmoderated spallation neutron beamline at the Weapons Neutron Research facility at Los Alamos was used in conjunction with a time-gated imaging system to measure the yield of a scintillating fiber array over several energy bands ranging from 1 to 15 MeV. The results and comparison to simulation are presented.


Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes.
The class II transactivator (CIITA) has been shown to be required for major histocompatibility complex (MHC) class II gene expression in B cells and its deficiency is responsible for a hereditary MHC class II deficiency. Here we show that CIITA is also involved in the inducible expression of class II genes upon interferon gamma (IFN-gamma) treatment. The expression of CIITA is also inducible with IFN-gamma before the induction of MHC class II mRNA. In addition, CIITA mRNA expression does not require new protein synthesis, although new protein synthesis is necessary for the transcription of class II. This suggests that synthesis of new CIITA protein may be essential to induce class II gene expression. We also showed that the JAK1 protein tyrosine kinase activity is required to induce the expression of CIITA upon IFN-gamma stimulation. This finding indicates that CIITA is part of the signaling cascade from the IFN-gamma receptor to the activation of class II genes. In addition, the expression of CIITA is sufficient to activate class II genes in the absence of IFN-gamma stimulation suggesting that CIITA is the major regulatory factor for the inducible expression of class II genes. Together, these data suggest that CIITA is the IFN-inducible cycloheximide sensitive factor previously shown to be required for the induction of MHC class II gene expression.


Mendel's controlled pollination experiments in Mirabilis jalapa confirmed his discovery of the gamete theory of inheritance in Pisum.
The historian studies revealed during Mendel's later research period when mainly focusing on the constant hybrid in Hieracium, he had to be intervened to conduct the controlled pollination experiments in Mirabilis jalapa. Two letters to Nageli recorded the experimental aim was to disprove Darwin's opinion regarding three pollen grains required for one fertilization (note: that could completely destroy his previous discovery of segregation inheritance in variable hybrid in Pisum, for it was expressed in a mathematical equation). The experimental results of single pollen grain pollination confirmed the referenced view of one pollen cell uniting one egg cell in plant fertilization; the further pedigree introduction of the single and of the designed two pollen grain experiment succeeded in exemplifying that one hereditary factor carried by one gamete (pollen cell or egg cell) can independently transmit a trait to offspring. Here we coined the observation as the Gamete Theory of Inheritance. Remarkably, in contrast with the bulked pollination experiment, in this system, Mendel could easily manipulate a hereditary factor by merely taking a gamete as a carrier. Then, Mendel's work in M. jalapa together with the previous Pisum study was able to jointly suppport his second lecture content that regarded "gamete formation, fertilization, and seed development" and also regarded hereditary factors in the processes. All in all, the 1866 paper was published during a rapid burst of interest in hybrid species likely induced by Darwin, and Mendel's attempts at accommodation of the two incompatible inheritances of segregation in variable hybrids versus of nonsegregation in constant hybrids might be responsible for some historical controversies when understanding his discovery of inheritance.


Erythropoietin increases macrophage-mediated T cell suppression.
Erythropoietin (EPO), used to treat anemia in cancer patients, has been reported to accelerate tumor progression and increase mortality. Research of the mechanism for this effect has focused upon EPOR expression by tumor cells. We model the high macrophage to lymphocyte ratio found in tumor microenvironments (TMEs) by culturing peritoneal cavity (PerC) cells that naturally have a high macrophage to T cell ratio. Following TCR ligation, C57BL/6J PerC T cell proliferation is suppressed due to IFNγ-triggered inducible nitric oxide synthase (iNOS) expression. EPO was tested in the PerC culture model and found to increase T cell suppression. This effect could be abrogated by inhibiting iNOS by enzyme inhibition, genetic ablation, or blocking IFNγ signaling. Flow cytometry revealed the EPOR on CD11b(+)F4/80(+) macrophages. These results suggest that EPO could increase T cell suppression in the TME by acting directly on macrophages.


Influence of tongue pressure and width on tongue indentation formation.
The purpose of this study was to clarify which physiological and anatomical factors were involved in the formation of tongue indentations, which are believed to be a clinical sign of clenching. Twenty-four dentulous subjects were investigated. They were divided into two groups, depending on the presence or absence of tongue indentations: (i) a tongue indentation group and (ii) a no tongue indentation group. Intraoral appliances containing a small pressure sensor were placed at the lingual surfaces of the upper and lower right first molars. Lingual pressure on the lingual surfaces of the upper and lower right first molars was then recorded under different conditions. The tasks selected as physiological factors to be recorded were: (i) silent reading at rest for 10 min, (ii) maximum voluntary clenching (MVC) for 5 s, (iii) 10% of MVC for 1 min and (iv) swallowing. The results for all tasks were compared between groups. Tongue width and dental arch width were also measured as anatomical factors. No significant differences were found between groups during silent reading at rest, clenching, swallowing, or in tongue pressure integration during silent reading at rest. However, a significant difference was found in terms of tongue width (P < 0.05). These results indicate that neither volume of lingual pressure exerted on the lingual surface of the teeth during rest, clenching, nor swallowing are related to the formation of tongue indentations. The results do suggest; however, that tongue width at rest plays an important role in the formation of tongue indentations.


Genetic parameters for fur quality graded on live animals and dried pelts of American mink (Neovison vison).
Fur quality and skin size are integral qualities in the mink industry and are main determinants of sales price and subsequent income for mink fur producers. Parental animals of future generations are selected based on quality grading from live animals, but selection response is obtained from dried skins sold after pelting. In this study, we evaluated traits assessed during live grading and pelt traits examined on dried skins to determine correlation between live and pelt traits. Grading traits and body weight were measured during live animal grading for 9,539 Brown American mink, and pelt quality traits and skin size were evaluated on 8,385 dried mink skins after pelting. Data were sampled from 2 yearly production cycles. Genetic parameters were estimated using the REML method implemented in the DMU package. Heritabilities and proportions of litter variance were calculated from estimated variance components for all traits, and genetic and phenotypic correlations between all traits were estimated in a series of bivariate analyses. Heritability estimates for live grading traits ranged from 0.06 to 0.28, heritability estimates for pelt quality traits ranged from 0.20 to 0.30, and finally heritability estimates for body size traits ranged from 0.43 to 0.48. Skin size and body weight were regarded as different traits for the two sexes and were therefore analysed for each sex separately. Genetic correlations between grading traits exhibited a range of 0.30-0.99 and genetic correlations between pelt quality traits ranged from 0.38 to 0.86. Genetic correlations between quality, wool density and silky appearance evaluated during live animal grading and on dried skin after pelting were 0.74, 0.41 and 0.33, respectively. Skin size and body weight were negatively correlated with pelt quality traits and ranged from -0.55 to -0.25. Using standard selection index theory and combined information from both live grading and skin evaluation increase of reliability of selection ranged from 0.6% to 14%. Due to moderate genetic correlations between traits evaluated during live grading and on dried skins, and negative correlations between pelt quality traits and body size, we concluded that traits should be selected simultaneously.


Influence of a thermally bloomed atmosphere on target image quality.
An assessment is made of the impact of a thermally bloomed atmosphere on target image quality. The steady-state phase perturbations due to blooming and the effects of the distortion on return wave fronts are determined using a physical optics propagation code. Return target images for several realistic scenarios are reconstructed based on the incoherent point spread function for each isoplanatic region of the object (target) plane. The behavior of the images is discussed with respect to wavelength sensitivity, blur, distortion, and degradation in peak irradiance. The wave-optics approach is shown to agree with published experimental results.


Functional role of CD105 in TGF-beta1 signalling in murine and human endothelial cells.
Angiogenesis is important in health and several disease states. CD105 is a proliferation-associated and hypoxia-inducible transmembrane protein abundantly expressed in angiogenic endothelial cells. CD105 is a receptor for transforming growth factors (TGF)-beta1 and -beta3. The exact mechanisms for CD105 regulation of vascular development have not been fully elucidated. In this study, an antisense approach to create a murine and a human stably transfected endothelial cell line expressing a reduction in CD105 protein was used. We showed that inhibition of CD105 in cultured murine and human endothelial cells enhanced the ability of TGF-beta1 to suppress growth and migration, and influenced TGF-beta1 promoter activity. TGF-beta1 not only reduced the length of the capillary-like structures, but also caused mortality in CD105-deficient murine antisense cells compared to control cultures. To determine whether CD105 affected TGF-beta1-induced gene expression, a luciferase assay in transiently transfected cells with p3TP-Lux promoter constructs was performed. Both murine and human antisense transfectants showed a significant increase in p3TP-Lux promoter activity. Further studies on the functional importance of CD105 was undertaken in irradiated normoxic and hypoxic cells. The levels of pro- and anti-apoptotic markers were also evaluated. There was an increase in pro-apoptotic marker (p53), but a reduction in anti-apoptotic marker (Bcl-2) in CD105-deficient cells. These results provide direct evidence that CD105 antagonises the inhibitory effects of TGF-beta1 on human and murine vascular endothelial cells and that normal cellular levels of CD105 are required for the formation of new blood vessels.


Fitz-Hugh-Curtis Syndrome: single centre experiences.
This study was conducted to report 10 cases of Fitz-Hugh-Curtis Syndrome (FHCS) diagnosed with CT and 101 cases of FHCS-like lesion that suggested perihepatitis during laparoscopic surgery. We reviewed retrospectively the images of 3,674 laparoscopies for obstetrical and gynaecological diseases and analysed 10 cases of FHCS diagnosed by clinical patterns and CT. All the 10 cases showed liver capsular enhancement on CT. Among the 3,674 laparoscopies, we found 101 cases (2.7%) with FHCS like lesion. Among them, 23 cases were during laparoscopic procedure for endometriosis, 16 for gynaecological malignant tumours, 16 for benign adnexal diseases excluding endometriosis, 13 for uterine leiomyoma, 7 for pelvic inflammatory disease, 2 had peritoneal tuberculosis and 21 for other gynaecological diseases. Further consideration should be given for the causes of FHCS other than N. gonorrhoeae and C. trachomatis. Because FHCS may represent various clinical phases, other considerations and clinical classifications are necessary for treatment.


Gluten-free diet: a new strategy for management of painful endometriosis related symptoms?
Pelvic pain affects 4% to 39% of women and accounts for 10-40% of all outpatient gynecologic visits. The etiology of painful endometriosis-related has not been fully delineated. No studies have been published concerning gluten-free diet administered to achieved relief of painful symptoms endometriosis-related. The aim of this retrospective study was to evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of gluten-free diet in a follow-up of 12 months in patients with chronic pelvic pain endometriosis-related. Two hundred seven patients with severe painful endometriosis-related symptoms entered the study. At enrolment time, the baseline values of painful symptoms were assessed by Visual Analogue Scale (VAS) for dysmenorrhoea, non-menstrual pelvic pain, and dyspareunia. According to VAS, pain severity was scored from 0-10; 0 indicating the absence of pain, and 1-4, 5-7 and 8-10 mild, moderate and severe respectively. A gluten-free diet was submitted to all patients and a new evaluation was performed after 12 months of diet. Student t test was used for statistical analysis. At 12 month follow-up, 156 patients (75%) reported statistically significant change in painful symptoms (P<0.005), 51 patients (25%) reported not improvement of symptoms. No patients reported worsening of pain. A considerable increase of scores for all domains of physical functioning, general health perception, vitality, social functioning, and mental health was observed in all patients (P<0.005). In our experience, painful symptoms of endometriosis decrease after 12 months of gluten free diet.


The Anterolateral Triangle: Implications for a Transnasal Prelacrimal Approach to the Floor of the Middle Cranial Fossa.
The anterolateral triangle enclosed by the foramen rotundum and foramen ovale constitutes part of the floor of the middle cranial fossa (MCF). To assess the feasibility of a transnasal prelacrimal approach for accessing the floor of MCF via an anterolateral triangle corridor and to determine the extent of maximal exposure while safeguarding neurovascular structures. A transnasal prelacrimal approach was performed in 5 cadaveric specimens (10 sides). Following the identification of foramen rotundum and foramen ovale, the bony ridge between 2 was drilled to expose the MCF. The temporal lobe dura was then elevated laterally, and the distances from foramen ovale to the respective borders of the area of the MCF window were measured using a surgical navigation device. The MCF was exposed with a 0° scope in all specimens also exposing significant landmarks including the middle meningeal artery, greater superficial petrosal nerve, superior petrous sinus, and arcuate eminence. Average distances from foramen ovale to the anterior, posterior, and lateral exposed borders were 22.86 ± 1.87 mm, 27.24 ± 0.94 mm, and 24.23 ± 1.61 mm, respectively. The average area of exposed MCF window was 554.12 ± 60.22 mm2. Preservation of vidian nerve, greater palatine nerve, lateral nasal wall, and nasolacrimal duct was possible in all 10 sides. It is feasible to access the floor of MCF via an endoscopic transnasal prelacrimal approach with seemingly low risk.


Confronting abusers: the opinions of clinicians and survivors.
Confrontation of an abuser is often regarded as a powerful process in clinical work with adult survivors of childhood sexual abuse. This paper explores direct and symbolic forms of survivors confronting their abusers via a review of the current literature and the self-report of 12 female survivors, post-therapy. Six of the survivors had chosen to directly confront their abusers and six had not. Their experiences and opinions are presented together with a discussion of important issues within this area and the need for further research.


Transition metal complex assisted Csp3-F bond formation.
Fluoroorganic compounds have attracted significant attention in various fields, such as pharmaceutical, agricultural chemistry, and materials science, as a result of their unique physical, chemical, and physiological properties. Consequently, extensive efforts have been devoted to the site-specific synthesis of organofluorine compounds. In recent years, transition-metal-mediated C-F bond formation has emerged as a powerful method for fabrication of these compounds. this Perspective mainly focuses on the most recent advances in transition-metal-assisted synthesis of alkyl fluorides.


BdVRN1 Expression Confers Flowering Competency and Is Negatively Correlated with Freezing Tolerance in Brachypodium distachyon.
Vernalization is an essential process by which many temperate plant species acquire competence for flowering. Brachypodium distachyon is a model plant for temperate grasses including many cool-season forage and turfgrasses and cereals. Grasses with spring growth habit do not require vernalization for flowering and are typically less winter hardy. Yet the connection between vernalization and freezing tolerance remain unclear. The diverse requirement of vernalization for flowering makes it an ideal choice for studying the relationship between vernalization and freezing tolerance. Here, we isolated and analyzed the spatial and temporal expression patterns of two vernalization related homologous genes, BdVRN1 and BdVRN3 in Bd21, a non-vernalization-requiring accession, and Bd29-1, an accession shown to be vernalization-requiring. We showed that expression of BdVRN1 and BdVRN3 is independent of vernalization in Bd21, but is vernalization dependent in Bd29-1. Moreover, vernalization-induced expression of BdVRN1 appears to precede that of BdVRN3 in Bd29-1. Bd21 RNAi knockdown mutants for BdVRN1 conferred vernalization requirement for flowering, and reduced the expression of BdVRN3. Both Bd29-1 and the BdVRN1 RNAi mutants of Bd21 exhibited reduced freezing tolerance upon vernalization treatment. Cold-responsive genes BdCBF2, BdCBF3, BdCBF5, BdCBF6, and BdDREB2A were all constitutively expressed at a high level in the BdVRN1 RNAi mutants of Bd21. Taken together, our results suggest that expression of BdVRN1 promotes flowering by upregulating BdVRN3, and gaining the competency for flowering reduces freezing tolerance in Brachypodium.


[Dysphagia and Sonography: what Association?].
Achalasia is a primary esophageal motility disorder characterized by dysphagia, chest pain, and drug-resistant reflux symptoms. A detailed anamnesis and esophageal manometry are essential tools for a correct diagnosis. We present a case of a 31 years old woman with typical achalasia symptoms misdiagnosed for many years due to a complex background picture. Despite the evolution in medical sciences, this clinical case underlines the cornerstones of medical profession: patient-physician relation and bedside clinical approach. At the same time, it confirms the increasing role of ultrasonography as a simple but essential tool for a complete general-internal medicine evaluation.


A gene transcription signature of obesity in breast cancer.
Obesity is thought to contribute to worse disease outcome in breast cancer as a result of increased levels of adipocyte-secreted endocrine factors, insulin, and insulin-like growth factors (IGFs) that accelerate tumor cell proliferation and impair treatment response. We examined the effects of patient obesity on primary breast tumor gene expression, by profiling transcription of a set of 103 tumors for which the patients' body mass index (BMI) was ascertained. Sample profiles were stratified according to patients' obesity phenotype defined as normal (BMI < 25), overweight (BMI 25-29.9), or obese (BMI ≥ 30). Widespread gene expression alterations were evident in breast tumors from obese patients as compared to other tumors, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes. In multiple public expression data sets of breast cancers (representing > 1,500 patients), manifestation of the obesity signature patterns correlated with manifestation of a gene signature for IGF signaling and (to a lesser extent) with lower levels of estrogen receptor. In one patient cohort, manifestation of the obesity signature correlated with shorter time to metastases. A number of small molecules either induced or suppressed the obesity-associated transcriptional program in vitro; estrogens alpha-estradiol, levonorgestrel, and hexestrol induced the program, while several anti-parkinsonian agents targeting neurotransmitter receptor pathways repressed the program. Obesity in breast cancer patients appears to impact the gene expression patterns of the tumor (perhaps as a result of altered body chemistry). These results warrant further investigation of obesity-associated modifiers of breast cancer risk and disease outcome.


Yang-Mills origin of gravitational symmetries.
By regarding gravity as the convolution of left and right Yang-Mills theories together with a spectator scalar field in the biadjoint representation, we derive in linearized approximation, the gravitational symmetries of general covariance, p-form gauge invariance, local Lorentz invariance, and local supersymmetry from the flat space Yang-Mills symmetries of local gauge invariance and global super-Poincaré symmetry. As a concrete example, we focus on the new minimal (12+12) off shell version of simple four-dimensional supergravity obtained by tensoring the off shell Yang-Mills multiplets (4+4, N_{L}=1) and (3+0, N_{R}=0).


Reduction of the excess sludge production by biological alternating process: real application results and metabolic uncoupling mechanism.
The biological solution proposed to reduce the wasted sludge production is based on a process of alternating phases realized in a specific reactor (alternate cycles in sludge line (ACSL)) where a quote of the recycle sludge is treated and sent back to the main activated sludge process. The ACSL process was applied in two urban wastewater treatment plants (WWTPs). The reduction was tested by changing the hydraulic retention time and the conditions of oxidation reduction potential. The main mechanism of the process is recognized in the metabolic uncoupling. In fact, an increase in the specific oxygen uptake rate in the biological reactors was recorded (up to 20 mg/g VSS/h), which was stimulated by the fasting condition in the ACSL. The process is able to reduce the observed sludge yield on average of 25-30% with final average values reaching 0.179 kg VSS/kg chemical oxygen demand (COD) for WWTP1 and 0.117 kg VSS/kg COD for WWTP2.


Pathology of benign prostatic hyperplasia. Insight into etiology.
Morphometric studies of prostates with benign hyperplasia (BPH) have revealed features that may help clarify the disease's natural history and biologic behavior. Hyperplasia arises within a small anatomic region having precise boundaries and containing an unusual juxtaposition of glandular and stromal elements. Diffuse non-nodular enlargement of the transition zone is the commonest morphologic feature of BPH, but nodules show a greater potential for growth and comprise most of the tissue in large (more than 50-gm) resection specimens. Most nodules are predominantly glandular, with features that suggest a pathogenetic role of induction of embryonic-type stroma.


Severe hematologic temozolomide-related toxicity and lifethreatening infections.
Glioblastoma is the most frequent primary malignant brain tumor in adults. With the number of symptoms and signs, it belongs to diseases where a lot of treatment modalities are often applied. A standard treatment for patients with glioblastoma includes surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide. Each type of treatment has its own toxicity. Temozolomide is an oral alkylating cytotoxic drug and like any other alkylating agent can induce side effects. Although temozolomide is generally a well tolerated drug, with rare severe toxic effects, sometimes certain toxicities can overcome the life risk of the underlying malignancy. By reviewing the literature, we have selected the cases with severe clinical presentation where some of them had a lethal outcome and we have chosen to present them in this article. In some patients with noticeable hematological toxic effects, as well as those with serious infections, attention must be paid to their treatment, as toxic effects can deepen and develop new toxicity, which all lead to a vicious circle without a favorable outcome. Preventive use of antiviral drugs should be considered before the treatment with temozolomide in patients with a positive history of viral infections such as Hepatitis B infection. In order to prevent rare but possible opportunistic infections, it is necessary to familiarize the patients with the treatment, toxicity and rare opportunistic infections. These infections can be triggered by various factors from the nearest environment, including both domestic and wild animals and pets.


Rapid Microsatellite Marker Development Using Next Generation Pyrosequencing to Inform Invasive Burmese Python-Python molurus bivittatus-Management.
Invasive species represent an increasing threat to native ecosystems, harming indigenous taxa through predation, habitat modification, cross-species hybridization and alteration of ecosystem processes. Additionally, high economic costs are associated with environmental damage, restoration and control measures. The Burmese python, Python molurus bivittatus, is one of the most notable invasive species in the US, due to the threat it poses to imperiled species and the Greater Everglades ecosystem. To address population structure and relatedness, next generation sequencing was used to rapidly produce species-specific microsatellite loci. The Roche 454 GS-FLX Titanium platform provided 6616 di-, tri- and tetra-nucleotide repeats in 117,516 sequences. Using stringent criteria, 24 of 26 selected tri- and tetra-nucleotide loci were polymerase chain reaction (PCR) amplified and 18 were polymorphic. An additional six cross-species loci were amplified, and the resulting 24 loci were incorporated into eight PCR multiplexes. Multi-locus genotypes yielded an average of 61% (39%-77%) heterozygosity and 3.7 (2-6) alleles per locus. Population-level studies using the developed microsatellites will track the invasion front and monitor population-suppression dynamics. Additionally, cross-species amplification was detected in the invasive Ball, P. regius, and Northern African python, P. sebae. These markers can be used to address the hybridization potential of Burmese pythons and the larger, more aggressive P. sebae.


Functional characterization of BnHSFA4a as a heat shock transcription factor in controlling the re-establishment of desiccation tolerance in seeds.
Desiccation tolerance (DT) is the crucial ability of seeds to resist desiccation. However, the regulatory mechanisms of seed DT are not fully understood. In this study, two heat shock cis-elements (HSEs) were identified in the Brassica napus galactinol synthase (BnGolS1) promoter and shown to bind the heat shock transcription factor A4a (BnHSFA4a). Transcriptional expression of BnHSFA4a was induced at the early stage of DT acquisition, prior to increased BnGolS1 activity and galactinol production. Ectopic overexpression of BnHSFA4a (oxBnHSFA4a) in Arabidopsis enhanced DT, particularly during DT re-establishment. OxBnHSFA4a up-regulated the expression of GolS1, GolS2, and raffinose synthase 2 (BnRS2) in Arabidopsis and increased the enzymatic activity of GolS and RS and the concentration of raffinose family oligosaccharides (RFOs). Additionally, the overexpression lines exhibited increased antioxidant abilities. In contrast, the Arabidopsis mutant athsfa4a was more sensitive to dehydration, showing decreases in the efficiency of DT re-establishment, RFO contents, and oxidation resistance. Complementation analysis indicated that DT was rescued in athsfa4a/BnHSFA4a seeds to similar levels compared with those of Col-0. Taken together, these results indicated that BnHSFA4a probably functions in the regulation of GolS expression and activity, and activation of the antioxidative system and other stress response factors to improve DT.


[Parameters for the assessment of inflammation of the anterior segment of the eye].
The authors examine general aspects of the assessment and evaluation of inflammation of the anterior segment of the eye, stressing above all the importance of accurate history taking and correct diagnostic approach. The also define general features of inflammatory processes and analyse the main and most modern instrumental techniques that are essential for precise assessment of clinical parameters of inflammatory conditions of the anterior segment of the eye.


Aspiration of Fractured Tracheostomy Tube in a Prone Positioned COVID-19 Patient: A Case Report and Review of the Literature.
A 61-year-old male patient diagnosed with Coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) was managed with tracheostomy and intermittent prone positioning in the intensive care unit. After a sudden deterioration, examination of tracheostomy tube (TT) and X-ray of the chest revealed that he had aspirated the fractured TT. The fractured tube was removed through the tracheostomy stoma using a rigid ventilating bronchoscope and forceps. Prone positioning is a beneficial postural therapy capable of improving patient oxygenation. However, it has some complications, like unplanned extubation and facial tissue injury. Percutaneous tracheostomy is also a valuable and safe procedure and has been increasingly performed in critical care patients, including those who suffer from COVID-19 ARDS. Fractures and aspiration of a tracheostomy tube can occur anytime after tracheostomy. We think prone positioning may contribute to the rupture and aspiration of the tracheostomy tube in this study.


Platelet gel: a new therapeutic tool with great potential.
Chronic wounds, such as diabetic foot ulcers, represent a serious clinical problem for patients and clinicians. Management of these wounds has a strong economic impact worldwide. Complications resulting from injuries are a frequent cause of morbidity and mortality. Chronic wounds lead to infections, painful dressings and prolonged hospitalisation. This results in poor patient Quality of Life and in high healthcare costs. Platelet concentrates (PC) are defined as autologous or allogeneic platelet derivatives with a platelet concentration higher than baseline. PC are widely used in different areas of Regenerative Medicine in order to enhance wound healing processes; they include platelet-rich plasma (PRP), platelet gel (PG), platelet-rich fibrin (PRF), serum eye drops (E-S), and PRP eye drops (E-PRP). This review highlights the use of platelet-rich plasma (PRP) and platelet gel (PG) preparation for clinical use.


Novel Synonymous and Frameshift Variants in the TRIP12 Gene Identified in 2 Chinese Patients With Intellectual Disability.
Clark-Baraitser syndrome is characterized by intellectual disability with or without autism spectrum disorders, speech delay, motor delay, behavioral abnormalities, and facial dysmorphism. It is caused by a heterozygous pathogenic variant in the thyroid hormone receptor interactor 12 (TRIP12) gene. However, loss of function and haploinsufficiency are the pathogenic mechanisms behind the TRIP12-related disorder. We conducted an exome sequencing analysis for 2 unrelated patients with moderate intellectual disability, speech delay, and motor delay. We identified 2 de novo TRIP12 mutations in these 2 patients. One patient had a frameshift duplication, whereas the other had a synonymous variant. Both patients presented with common features of the syndrome, but clinical heterogeneity has been also observed between them. For the synonymous variant, reverse transcription PCR in RNA extracted from leukocytes demonstrated the presence of a truncated messenger RNA (mRNA) transcript that skipped exon 12. This transcript escapes degradation at the mRNA level. To assess the effect of the synonymous substitute on TRIP12 proteolytic activity, the expression of 9 known responsive genes at the mRNA level was measured, of which 3 genes were upregulated at least 2-fold in the patient. We reported 2 patients with Clark-Baraitser syndrome caused by novel synonymous and frameshift variants in the TRIP12 gene, and our study expands the mutation spectrum of the TRIP12 gene. This study will help to improve our understanding of variable phenotypic presentations in TRIP12-related disorders.


Long-term aerobic exercise training in type two diabetic patients alters the expression of miRNA-223 and its corresponding target, the P2RY12 receptor, attenuating platelet function.
Type two diabetes mellitus (T2DM) patients are prone to develop atherothrombotic events due to platelet hyper-reactivity stemming from platelet miRNA-223 down-regulation and over-expression of its corresponding target, P2RY12. The study sought to determine the effects of long-term aerobic training on the expression levels of miRNA-223 and P2RY12 mRNA, and platelet function in T2DM patients. Twenty-four patients with T2DM (age, 60.0±2.8 yrs.) were selected and randomly divided into two groups: aerobic exercise training (AET, n = 12) and control (CON, n = 12). The AET protocol was performed with moderate intensity for 12 weeks, while patients in the CON group followed their usual routine. Weight, body mass index (BMI), peak oxygen consumption (VO2peak), lipid profile, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), platelet miRNA-223 and P2RY12 expression were measured before and after the period. There was a significant improvement in body weight, BMI, VO2peak, FBG, HbA1c, and HOMA-IR, after 12 weeks of AET (P < 0.01). Platelet aggregation decreased significantly after 12 weeks in the AET group compared with the CON (P < 0.001) group. Platelets' miRNA-223 and P2RY12 were significantly up- and down-regulated after AET in comparison with the CON group (P < 0.05), respectively. Moreover, the relative expression of miRNA-223 and P2RY12 significantly correlated with FBG changes following the intervention. It can be concluded that long-term moderate-intensity aerobic training might be effective for reducing the occurrence of atherothrombotic events leading to premature death in T2DM patients through the modulation of miRNA-223, P2RY12 receptor expression, and platelet function.


Computed tomography versus aortography for preoperative evaluation of abdominal aortic aneurysm.
Twenty-eight patients with abdominal aortic aneurysm were examined by computed tomography (CT) and aortography. They subsequently underwent aneurysmectomy and reconstruction of the aorta. CT provided in most of the cases the same or more accurate preoperative information than aortography. CT is comfortable for the patient, less invasive and faster than aortography and can be done as an outpatient procedure. Thus, we recommend CT to be the primary method for preoperative evaluation of abdominal aortic aneurysm. In selected cases aortography gives additional information regarding the relationship to the renal arteries (when the aorta is very tortuous), the occurrence of renal artery stenosis, and peripheral vascular disease.


Host preference of field-derived Schistosoma mansoni is influenced by snail host compatibility and infection status.
Schistosome parasites cause a chronic inflammatory disease in humans, and recent studies have emphasized the importance of control programs for understanding the aquatic phases of schistosomiasis transmission. The host-seeking behavior of larval schistosomes (miracidia) for their snail intermediate hosts plays a critical role in parasite transmission. Using field-derived strains of Kenyan snails and parasites, we tested two main hypotheses: (1) Parasites prefer the most compatible host, and (2) parasites avoid hosts that are already infected. We tested preference to three Biomphalaria host snail taxa (B. pfeifferi, B. sudanica, and B. choanomphala), using allopatric and sympatric Schistosoma mansoni isolates and two different nonhost snail species that co-occur with Biomphalaria, Bulinus globosus, and Physa acuta. We also tested whether schistosomes avoid snail hosts that are already infected by another trematode species and whether competitive dominance played a role in their behavior. Preference was assessed using two-way choice chambers and by visually counting parasites that moved toward competing stimuli. In pairwise comparisons, we found that S. mansoni did not always prefer the more compatible snail taxon, but never favored an incompatible host over a compatible host. While parasites preferred B. pfeifferi to the nonhost species B. globosus, they did not significantly prefer B. pfeifferi versus P. acuta, an introduced species in Kenya. Finally, we demonstrated that parasites avoid infected snails if the resident parasite was competitively dominant (Patagifer sp.), and preferred snails infected with subordinates (xiphidiocercariae) to uninfected snails. These results provide evidence of "fine tuning" in the ability of schistosome miracidia to detect hosts; however, they did not always select hosts that would maximize fitness. Appreciating such discriminatory abilities could lead to a better understanding of how ecosystem host and parasite diversity influences disease transmission and could provide novel control mechanisms to improve human health.


Cortico-cortical, cortico-striatal, and cortico-thalamic white matter fiber tracts generated in the macaque brain via dynamic programming.
Probabilistic methods have the potential to generate multiple and complex white matter fiber tracts in diffusion tensor imaging (DTI). Here, a method based on dynamic programming (DP) is introduced to reconstruct fibers pathways whose complex anatomical structures cannot be resolved beyond the resolution of standard DTI data. DP is based on optimizing a sequentially additive cost function derived from a Gaussian diffusion model whose covariance is defined by the diffusion tensor. DP is used to determine the optimal path between initial and terminal nodes by efficiently searching over all paths, connecting the nodes, and choosing the path in which the total probability is maximized. An ex vivo high-resolution scan of a macaque hemi-brain is used to demonstrate the advantages and limitations of DP. DP can generate fiber bundles between distant cortical areas (superior longitudinal fasciculi, arcuate fasciculus, uncinate fasciculus, and fronto-occipital fasciculus), neighboring cortical areas (dorsal and ventral banks of the principal sulcus), as well as cortical projections to the hippocampal formation (cingulum bundle), neostriatum (motor cortical projections to the putamen), thalamus (subcortical bundle), and hippocampal formation projections to the mammillary bodies via the fornix. Validation is established either by comparison with in vivo intracellular transport of horseradish peroxidase in another macaque monkey or by comparison with atlases. DP is able to generate known pathways, including crossing and kissing tracts. Thus, DP has the potential to enhance neuroimaging studies of cortical connectivity.


Changing the Properties of Multipotent Mesenchymal Stromal Cells by IFNγ Administration.
We studied changes in the population of human multipotent mesenchymal stromal cells activated by IFNγ. The cells were cultured under standard conditions; IFNγ was added in various concentrations for 4 h or over 2 passages. It was shown that the total cell production significantly decreased after long-term culturing with IFNγ, but 4-h exposure did not affect this parameter. After 4-h culturing, the expression levels of IDO1, CSF1, and IL-6 increased by 300, 7, and 2.4 times, respectively, and this increase persisted 1 and 2 days after removal of IFNγ from the culture medium. The expression of class I and II MHC (HLA) on cell surface practically did not change immediately after exposure to IFNγ, but during further culturing, HLA-ABC (MHC I) and HLA-DR (MHC II) expression significantly increased, which abolished the immune privilege in these cells, the property allowing clinical use of allogenic multipotent mesenchymal stromal cells. Multipotent mesenchymal stromal cells can suppress proliferation of lymphocytes. The degree of this suppression depends on individual properties of multipotent mesenchymal stromal cell donor. Treatment with IFNγ did not significantly affect the intensity of inhibition of lymphocyte proliferation by these cells.


Constipation: what does the patient mean?
Constipation is a very common complaint but, in the absence of a universally accepted definition, misunderstandings may result between doctor and patient. Two hundred and eighty-seven patients attending this hospital completed a questionnaire which attempted to establish what patients themselves mean by the term. Almost half considered constipation purely in terms of frequency of bowel action, without considering difficulty or pain on defaecation. Women were more likely to have infrequent bowel actions than men, and men more likely to consider such infrequency harmful. A quarter of respondents believed in the benefits of regular purgation, surprisingly with no difference in attitude between age groups, but men were much less likely to have heeded their own advice.


Life span development: intervention implications for concepts of aging.
The life span theory of development is based on the notion that development occurs at all ages. A person's developmental history influences his or her behavior later in life. Following this assumption, the ability of an elderly person to cope with health problems is related to past experience in coping with similar problems or life events. The goal of intervention related to life span development serves two purposes: to help individuals overlap positive health behaviors that will be sustained throughout life and to discuss the role and impact of life events on their ability to cope with later problems. The school health program provides an excellent vehicle for achieving these goals.


Mediation of enhanced transcription of the IL-10 gene in T cells, upon contact with human glioma cells, by Fas signaling through a protein kinase A-independent pathway.
Elevated expression of IL-10 has been frequently observed in tumor tissues and tumor-infiltrating cells. We show herein that transcription of the IL-10 gene in primary peripheral T cells and T cell lines is up-regulated upon contact with glioma cells without an induction of apoptosis in those T cells. Glioma-associated IL-10 induction was suppressed by interrupting the engagement of Fas and its ligand (Fas-L) with the antagonistic Ab, ZB4, by reducing Fas-L expression of glioma cells using the Fas-L-specific ribozyme, or by preventing cell-to-cell contact in a Transwell culture setting. Cross-linking of Fas with the agonistic Ab, CH-11, triggered apoptosis and enhanced the expression of IL-10 in Jurkat cells at the transcriptional and translational levels. Inhibiting caspase activities by caspase inhibitors, Z-VAD (Z-Val-Ala-Asp(Ome)-fluoromethylketone) and Z-IETD (Z-Ile-Glu(Ome)-Thr(Ome)-Asp(Ome)-fluoromethylketone), abolished this IL-10 induction in Jurkat cells. Intracellular staining detected IL-10 proteins in Fas-cross-linked Jurkat cells and in PHA-activated T cells. However, few IL-10 proteins were detectable in Jurkat cells cocultured with glioma cells, indicating a requirement of other factors for IL-10 production. Direct activation of protein kinase A (PKA) by forskolin elevated the transcription of IL-10 in Jurkat cells. However, KT5720, a selective PKA inhibitor, reduced neither anti-Fas-triggered nor glioma-associated IL-10 expression. Phosphorylation of cAMP response element binding protein and activating transcription factor-1 in Jurkat cells was not affected by coculturing with glioma cells or by anti-Fas treatment, further suggesting a PKA-independent pathway. In summary, our results demonstrate nonlethal cross-talk between tumor and immune cells leading to IL-10 dysregulation in T cells, which might contribute to Fas-L(+) tumor-associated immunosuppression.


Common mental disorders in pregnancy in the context of interpartner violence.
Pregnancy is generally described as a period with a high incidence of common mental disorders (CMD) in the life cycle of many women who incur the risk of developing mental problems including depression, post-traumatic stress and drug abuse. Our objective with this study was to gauge how the presence of violence in Portuguese pregnant women affected their psychopathology. One hundred and eighty-four pregnant outpatients of the Obstetrics and Gynaecology Department of the Hospital Pedro Hispano in Matosinhos, Oporto, Portugal with an average age of 29 and in their last 3 months of pregnancy were the subjects of this study. These participants were divided into two groups: one of abused women (n= 107) and another of non-abused women (n= 77). In order to be able to compare them, both groups were assessed with the Conflict Tactic Scale 2, the Brief Symptom Inventory and the Inventory of the Clinical Evaluation of Depression. It was observed that pregnant women who had suffered violence during pregnancy exhibited some form of CMD during pregnancy. Another important finding was the evidence of the negative impacts that domestic violence had on the mental health of women.


In situ detection of Bartonella henselae cells.
A new in situ hybridization technique was developed for identification of Bartonella henselae cells in cell suspension or in tissue sections. Use of highly specific probes labeled with either fluorescein or digoxigenin allows discrimination between B. henselae and closely related B. quintana cells. No cross-hybridization with other Bartonella or non-Bartonella species was observed. Besides its specificity it showed higher sensitivity as compared to PCR based detection methods. Moreover, its application allows direct observation of B. henselae in infected tissues.