Dynamics of the modulated distortions in confined nematic liquid crystals.
The peculiarities in the dynamics of the director reorientation in confined nematic liquid crystals (LCs) under the influence of a strong electric field E have been investigated theoretically based on the hydrodynamic theory including the director motion with appropriate boundary and initial conditions. Analysis of the numerical results for the turn-on process provides an evidence for the appearance of the spatially periodic patterns in confined LC film, only in response to the suddenly applied strong E. It has been shown that there is a threshold value of the amplitude of the thermal fluctuations of the director over the LC sample which provides the nonuniform rotation mode rather than the uniform one, whereas the lower values of the amplitude dominate the uniform mode. During the turn-off process, the reorientation of the director to the direction preferred by the surfaces is characterized by the complex destruction of the initially periodic structure to a monodomain state.


Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma.
A phase II trial of docetaxel was conducted to assess its efficacy and toxicity in patients with advanced transitional-cell carcinoma (TCC) who had failed to respond to prior cisplatin-based therapy. Thirty assessable patients who had failed to respond to or relapsed after one prior cisplatin-containing regimen were treated with docetaxel 100 mg/m2 over 1 hour, every 21 days. All patients were premedicated with dexamethasone and diphenhydramine to reduce allergic reactions. Reductions of subsequent doses were made for severe hematologic toxicity. Prophylactic hematopoietic growth factors were not used. Four of 30 patients (13.3%; 95% confidence interval [CI], 3.8% to 30.7%) demonstrated a partial response (PR), with durations of response ranging from 3 to 8 months. The estimated median survival duration for all patients is 9 months (95% CI, 6 to 12 months) with a median follow-up time of 14 months (range, 1 to 27). Hematologic toxicity included anemia, thrombocytopenia, neutropenia, and febrile neutropenia. Nonhematologic toxicity included alopecia and mucositis. Fluid retention was not observed and cutaneous toxicity was mild and infrequent. Dose reductions were necessary for adverse events in 18 patients (60%). Docetaxel is an active single agent in previously treated patients with TCC of the urothelial tract. Therapy was well tolerated in this patient population but myelosuppression was frequent. Further study in previously untreated patients, both alone and in combination, is warranted.


Course and extent of variation of equine infectious anemia virus during parallel persistent infections.
Comparisons of peptide and oligonucleotide maps of glycoproteins and RNA from nine isolates of equine infectious anemia virus (EIAV) that were generated during parallel infections of two Shetland ponies revealed that each isolate was structurally unique. Each EIAV isolate contained a unique subset of variant peptides, oligonucleotides, or both, indicating that structural variation in EIAV is a random and noncumulative process and that a large spectrum of possible EIAV variants can be generated in infected animals.


THE INFLUENCE OF TURBULENT FLOW ON THE SENSORY ASSESSMENT OF VISCOSITY IN THE MOUTH.
Low viscosity Newtonian fluids exhibit turbulence in a cone-plate viscometer at high rates of shear which are comparable to those operating in the mouth during sensory assessment of the viscosity of the same fluids. Saliva reduces this effect to some small extent, possibly due to its content of mucin and other proteinaceous substances. The net result is that these fluids appear to have a higher viscosity in the mouth than when they are examined in a viscometer at low rates of shear. Higher viscosity non-Newtonian food materials such as Carnation milk and ice cream do not exhibit turbulent flow, and the only effect exerted by saliva is a reduction in the viscosity at all rates of shear.


Sexual health as a survivorship issue for female cancer survivors.
As more and more people are successfully treated for and live longer with cancer, greater attention is being directed toward the survivorship needs of this population. Women treated for cancer often experience issues related to sexual health and intimacy, which are frequently cited as areas of concern, even among long-term survivors. Unfortunately, data suggest that providers infrequently discuss these issues. We reviewed a contemporary understanding of sexual health of women and the impact of treatment on both sexual function and intimacy. We also provide a review of the diagnosis using the newest classification put forth by the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, and potential treatments, including both endocrine and nonendocrine treatments that the general oncologist may be asked about when discussing sexual health with his or her patients.


Structural biology of transmembrane domains: efficient production and characterization of transmembrane peptides by NMR.
Structural characterization of transmembrane peptides (TMPs) is justified because transmembrane domains of membrane proteins appear to often function independently of the rest of the protein. However, the challenge in obtaining milligrams of isotopically labeled TMPs to study these highly hydrophobic peptides by nuclear magnetic resonance (NMR) is significant. In the present work, a protocol is developed to produce, isotopically label, and purify TMPs in high yield as well as to initially characterize the TMPs with CD and both solution and solid-state NMR. Six TMPs from three integral membrane proteins, CorA, M2, and KdpF, were studied. CorA and KdpF are from Mycobacterium tuberculosis, while M2 is from influenza A virus. Several milligrams of each of these TMPs ranging from 25 to 89 residues were obtained per liter of M9 culture. The initial structural characterization results showed that these peptides were well folded in both detergent micelles and lipid bilayer preparations. The high yield, the simplicity of purification, and the convenient protocol represents a suitable approach for NMR studies and a starting point for characterizing the transmembrane domains of membrane proteins.


Usefulness of (1) H-MRS in differentiating bilirubin encephalopathy from severe hyperbilirubinemia in neonates.
To evaluate the usefulness of (1) H-MRS in differentiating bilirubin encephalopathy from severe hyperbilirubinemia in neonates. There were 11 patients enrolled in the neonatal bilirubin encephalopathy (NBE) group, 8 patients in the neonatal hyperbilirubinemia (NH) group, and 9 healthy, age-matched neonates were included as controls. All patients and controls underwent (1) H-MRS and conventional magnetic resonance (MR) sequences. The spectroscopic regions of interest were the bilateral basal ganglia and the thalamus, and a spatial resolution of 1.0 cm(3) was obtained. Peak-area ratios of NAA/Cr and NAA/ Cho in the basal ganglia were found to be significantly lower for the NBE group compared with the NH and control groups (P < 0.05). In contrast, there was no significant difference in the NAA/Cr ratios calculated for basal ganglia of the NH and control groups. Peak-area ratios of NAA/Cr and NAA/Cho in the thalamus were decreased for the NBE group compared with the NH and control groups, but the differences were not significant (P > 0.05). There was a significant correlation between NAA/Cr ratios for basal ganglia and the total serum bilirubin (TSB) peak level in the NBE group (P < 0.05). (1) H-MRS is useful in the differential diagnosis of NBE from severe hyperbilirubinemia in neonates, especially when the symptoms of NBE are atypical (subtle) and MRI does not reveal clear abnormalities.


Bifunctional-nanotemplate assisted synthesis of nanoporous SrTiO₃ photocatalysts toward efficient degradation of organic pollutant.
Nanoporous SrTiO3 photocatalysts were fabricated via a novel technique, the nanotemplate assisted sol-gel hydrothermal reaction. In the alkaline-environment hydrothermal reaction, the SiO2 nanotemplate not only served as pore generator but also worked on adjusting the local reaction environment around the SrTiO3 nanocrystals. This contributed to a continuous modulation between the surface area and the crystallinity of the photocatalyst. The photocatalytic activities of the nanoporous SrTiO3 samples were evaluated by the degradation of gaseous isopropyl alcohol (IPA). Due to an optimal equilibrium between surface area and crystallinity, a SrTiO3 sample synthesized via adding 40% template (STO-SiO2-40%) showed the highest activity, which achieves 40 and 8 times of enhancement of CO2 evolution in comparison with the sample prepared without template and a commercial nano-SrTiO3, respectively. The photodegradation mechanism of IPA over this sample was also investigated in detail. This synthetic technique is also available to prepare the other nanoporous titanates, such as doped SrTiO3 samples and alkali-metal titanates.


Volatile compounds of Panax ginseng C.A. Meyer cultured with different cultivation methods.
The volatile compounds of Panax ginseng C.A. Meyer analyzed to interpret whether cultivation methods affect volatile compounds. The volatile compounds in Panax ginseng C.A. Meyer cultured with 3 different cultivation methods such as good agricultural practice, organic cultivation method, and general cultivation method were isolated by solid-phase microextraction fiber (polydimethylsiloxane 65 μm) and identified by gas chromatography mass spectrometry. Then, the scattering patterns of volatile compounds compared by principal component analysis. As the results, the 14 volatile compounds were identified from 30 ginseng samples and consisted mainly of sesquiterpene hydrocarbons. The differences among the different cultivation methods of the samples were obvious from the PC1 and PC2 scatter point plot. As the conclusion, the cultivation methods can affect to produce the volatile component of ginseng root. The organic and good agriculture practice cultivation can increase the ginseng characteristic volatile compounds.


Neoadjuvant therapy for pancreatic cancer.
Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with surgical resection of the primary tumour and systemic chemotherapy, which provides considerably longer overall survival (OS) durations than either modality alone. Regardless, most patients will have disease relapse owing to micrometastatic disease. Although currently a matter of some debate, considerable research interest has been focused on the role of neoadjuvant therapy for all forms of resectable PDAC. Whilst adjuvant combination chemotherapy remains the standard of care for patients with resectable PDAC, neoadjuvant chemotherapy seems to improve OS without necessarily increasing the resection rate in those with borderline-resectable disease. Furthermore, around 20% of patients with unresectable non-metastatic PDAC might undergo resection following 4-6 months of induction combination chemotherapy with or without radiotherapy, even in the absence of a clear radiological response, leading to improved OS outcomes in this group. Distinct molecular and biological responses to different types of therapies need to be better understood in order to enable the optimal sequencing of specific treatment modalities to further improve OS. In this Review, we describe current treatment strategies for the various clinical stages of PDAC and discuss developments that are likely to determine the optimal sequence of multimodality therapies by integrating the fundamental clinical and molecular features of the cancer.


MR guidance of laser disc decompression: preliminary in vivo experience.
The purpose of this study was to perform percutaneous laser disc decompression (PLDD) under MR guidance in an open configuration 0. 5-T MR system. Following failed conservative treatment for 6 months, eight patients with contained disc herniations were enrolled in the study. Following MR guided introduction of the laser fiber into the targeted disc space, the laser-induced temperature distribution was visualized using a color-coded subtraction technique based on a T1-weighted GRE sequence. In seven patients PLDD could be performed. In all cases laser effects were depicted by MR. In this regard the color-coded technique was found to be superior to conventional magnitude images. Whereas no apparent decrease in the extent of herniation was discovered immediately following PLDD, T2-weighted FSE images showed signal intensity alterations in two of the seven patients. Clinical evaluation, obtained 3-4 months after PLDD, revealed a fair (n = 2) or good (n = 4) response to the treatment. One patient showed no change in symptoms. MR guidance and monitoring of PLDD is feasible within an open 0.5-T system and seems to render PLDD more safe and controllable.


The structure of ubiquitinated histone H2B.
Ubiquitinated histone H2B (uH2B) has been purified from both calf and pig thymus by exclusion chromatography in 7 M urea. Digestion of uH2B with Staphylococcus aureus V8 protease yielded the peptide 114-125 containing the ubiquitin moiety. Further digestion of this peptide with trypsin removed the ubiquitin and three H2B residues from the N-terminus. Edman degradations of both peptides established that ubiquitin is attached to the epsilon-amino group of lysine 120 in both calf and pig uH2B by an iso-peptide bond to the C-terminal glycine 76 of ubiquitin.


Characteristics predictive of response to collagenase clostridium histolyticum for Peyronie's disease: a review of the literature.
To evaluate characteristics predictive of successful treatment outcomes of Peyronie's disease (PD) with collagenase clostridium histolyticum (CCH) METHODS: CCH is the only FDA-approved medication for treating PD. We reviewed the literature that addresses pre-treatment clinical characteristics that may predict favorable response to CCH therapy. Despite significant heterogeneity in reporting treatment success, we identified four well-studied characteristics that may be predictive of favorable response to CCH therapy: baseline penile curvature, baseline IIEF, duration of PD, and presence of calcification. CCH demonstrated a favorable response in those with pre-treatment curvature 30°-60°, longer duration of disease, mild to moderate baseline sexual function, and low calcification within plaques. Of all factors, calcification is emerging as the most significant factor likely because CCH is unable to degrade the calcified plaques. There is difficulty interpreting results because of differences in reporting outcomes. Some studies compared treatment groups to placebo, others reported changes in curvature, while others reported > 20% curvature correction as treatment success. Additionally, not all studies reported outcomes after completion of four cycles of CCH, and recent studies utilized a shortened, high dose, modified protocol. The ideal candidate for CCH therapy remains elusive. Based on the available literature, the man with PD who will have the greatest chance of curvature improvement will have curvature between 30° and 60°, longer duration of disease, an IIEF > 17, no calcification, and set to receive all four cycles. For a greater understanding of CCH treatment success in PD, prospectively collected registry reporting standardized outcomes are needed.


[Status of alpha 1-adrenergic regulation of stroke volume during hypokinesia in the rat].
The positive effect of phenylephrine (PE) on stroke volume (SV) was 3 to 5 times weaker in the rats exposed to hypokinesia for 30 days as compared to the controls. After obsidan blockade of beta-adrenoreceptors SV increased in both groups and the intergroup differences in the PE effect remained significant but less pronounced. This can be attributed to a greater effectiveness of PE after obsidan administration during hypokinesia. Correlation analysis showed that the weak effects of PE on SV were potentiated by obsidan (potentiation was the stronger the weaker the effects) while the distinct effects were on the contrary inhibited. This demonstrates the synergy--antagonism relationships in the PE and obsidan interaction and seems to indicate that the common site of their action is alpha 1-adrenoreceptors. After phentolamine injections the PE effect on SV was not found. In this situation SV decreased; the SV decrease as well as its increase under the action of obsidan was less significant in the hypokinetic than in the control rats. The above investigation suggests that the activity of alpha 1-adrenoreceptors involved in the actualization of positive effects of agonists on SV is considerably lower during hypokinesia.


Pre-exposure to cocaine or morphine attenuates taste avoidance conditioning in adolescent rats: Drug specificity in the US pre-exposure effect.
Although the attenuating effects of drug history on conditioned taste avoidance (CTA) learning have been widely investigated in adults, such effects in adolescents have not been well characterized. Recent research has suggested that the display of the drug pre-exposure effect during adolescence may be drug dependent given that pre-exposure to ethanol attenuates subsequent conditioning, whereas pre-exposure to the classic emetic lithium chloride (LiCl) fails to do so. The present study began investigating the possible drug-dependent nature of the effects of drug pre-exposure by pre-exposing and conditioning adolescent male Sprague-Dawley rats to drugs from two additional classes, specifically psychostimulants (cocaine; Experiment 1) and opioids (morphine; Experiment 2). Consistent with prior work with ethanol (but not LiCl), prior exposure to both cocaine and morphine attenuated taste avoidance induced by these compounds. Although this work supports the view of drug-dependent pre-exposure effects on taste avoidance learning during adolescence, research is needed to assess its mechanisms.


Functional roles of glycogene and N-glycan in multidrug resistance of human breast cancer cells.
Drug resistance is a major problem in cancer chemotherapy. Aberrant glycosylation has been known to be associated with cancer chemoresistance. Aim of this work is to investigate the alterations of glycogene and N-glycan involved in multidrug resistance (MDR) in human breast cancer cell lines. Using real-time polymerase chain reaction (PCR) for quantification of glycogenes, fluorescein isothiocyanate (FITC)-lectin binding for glycan profiling, and mass spectrometry for N-glycan composition, the expression of glycogenes, glycan profiling, and N-glycan composition differed between drug-resistant MCF/ADR cells and the parental MCF-7 line. Further analysis of the N-glycan regulation by tunicamycin (TM) application or PNGase F treatment in MCF/ADR cells showed partial inhibition of the N-glycan biosynthesis and increased sensitivity to chemotherapeutic drugs dramatically both in vitro and in vivo. Using an RNA interference strategy, we showed that the downregulation of MGAT5 in MCF/ADR cells could enhance the chemosensitivity to antitumor drugs both in vitro and in vivo. Conversely, a stable high expression of MGAT5 in MCF-7 cells could increase resistance to chemotherapeutic drugs both in vitro and in vivo. In conclusion, the alterations of glycogene and N-glycan in human breast cancer cells correlate with tumor sensitivity to chemotherapeutic drug and have significant implications for the development of new treatment strategies. © 2013 IUBMB Life, 65(5):409-422, 2013.


The Context of Sexual Risk Behaviour Among Men Who Have Sex with Men Seeking PrEP, and the Impact of PrEP on Sexual Behaviour.
There are still important gaps in our understanding of how people will incorporate PrEP into their existing HIV prevention strategies. In this paper, we explore how PrEP use impacted existing sexual risk behaviours and risk reduction strategies using qualitative data from the PROUD study. From February 2014 to January 2016, we conducted 41 in-depth interviews with gay, bisexual and other men who have sex with men (GBMSM) enrolled in the PROUD PrEP study at sexual health clinics in England. The interviews were conducted in English and were audio-recorded. The recordings were transcribed, coded and analysed using framework analysis. In the interviews, we explored participants' sexual behaviour before joining the study and among those using or who had used PrEP, changes to sexual behaviour after starting PrEP. Participants described the risk behaviour and management strategies before using PrEP, which included irregular condom use, sero-sorting, and strategic positioning. Participants described their sexual risk taking before initiating PrEP in the context of the sexualised use of drugs, geographical spaces linked with higher risk sexual norms, and digitised sexual networking, as well as problematic psychological factors that exacerbated risk taking. The findings highlight that in the main, individuals who were already having frequent condomless sex, added PrEP to the existing range of risk management strategies, influencing the boundaries of the 'rules' for some but not all. While approximately half the participants reduced other risk reduction strategies after starting PrEP, the other half did not alter their behaviours. PrEP provided an additional HIV prevention option to a cohort of GBMSM at high risk of HIV due to inconsistent use of other prevention options. In summary, PrEP provides a critical and necessary additional HIV prevention option that individuals can add to existing strategies in order to enhance protection, at least from HIV. As a daily pill, PrEP offers protection in the context of the sex cultures associated with sexualised drug use, digitised sexual applications and shifting social norms around sexual fulfilment and risk taking. PrEP can offer short or longer-term options for individuals as their sexual desires change over their life course offering protection from HIV during periods of heightened risk. PrEP should not be perceived or positioned in opposition to the existing HIV prevention toolkit, but rather as additive and as a tool that can and is having a substantial impact on HIV.


Partitioning solvophobic and dispersion forces in alkyl and perfluoroalkyl cohesion.
Fluorocarbons often have distinct miscibility properties compared to their nonfluorinated analogues. These differences may be attributed to van der Waals dispersion forces or solvophobic effects, but their contributions are notoriously difficult to separate in molecular recognition processes. Here, molecular torsion balances were used to compare cohesive alkyl and perfluoroalkyl interactions in a range of solvents. A simple linear regression enabled the energetic partitioning of solvophobic and van der Waals forces in the self-association of apolar chains. The contributions of dispersion interactions in apolar cohesion were found to be strongly attenuated in solution compared to the gas phase, but still play a major role in fluorous and organic solvents. In contrast, solvophobic effects were found to be dominant in driving the association of apolar chains in aqueous solution. The results are expected to assist the computational modelling of van der Waals forces in solution.


Novel bioprinted 3D model to human fibrosis investigation.
Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen. After stimulation by Transforming Growth factor beta (TGFβ), embedded cells differentiated into myofibroblasts and enhanced the contractile activity, as confirmed by the high level of α - smooth muscle actin (αSMA) and F-actin expression. As functional assays, SEM analysis revealed that after TGFβ stimulus the 3D microarchitecture of the scaffold was dramatically remolded with an increased fibronectin deposition with an abnormal collagen fibrillar pattern. Picrius Sirius Red staining additionally revealed that TGFβ stimulation enhanced of two logarithm the collagen fibrils neoformation in comparison with control. These data indicate that by bioprinting technology, it is possible to generate a reproducible and functional 3D platform to mimic fibrosis as key tool for drug discovery and impacting on animal experimentation and reducing costs and time in addressing fibrosis.


[Comparison of the cytotoxicity of five constituents from Pteris semipinnata L. in vitro and the analysis of their structure-activity relationships].
The antitumor constituents were isolated from Pteris semipinnata L. (PsL), a Chinese traditional herb, and screened using tetrazolium salt (MTT) method. Their cytotoxic effects in vitro on several human tumor cell lines were studied. Compounds 5F, 6F, A and the ethanolic extract of PsL (PSE) were shown to have strong cytotoxicity against five cell lines: human liver adenocarcinoma cell line (HePG II), human lung adenocarcinom a cell line (SPC-A-1), human gastric adenocarcinoma cell line (MGC-803), human nasopharyngeal carcinoma cells in low differentiation (CNE-2Z) and human liver adenocarcinoma cell line (BEL-7402) in different degrees in a dose-dependent manner; compound 6F was the most active one, whose IC50 after 72 h treatment for the above five cell lines were 0.343 +/- 0.003, 0.115 +/- 0.022, 0.590 +/- 0.032, 0.328 +/- 0.066 and 0.221 +/- 0.058 microgram.ml-1, respectively. Compounds A and 5F were less active; no cytotoxicity of compounds 4F and B were detected on the five cell lines. Analysis of the relationship between structure and activity revealed that the antitumor activity portion in the structure is the alpha, beta-methylene cyclopentanone moiety, and the site and number of the hydroxy groups affect the cytotoxicity of these agents significantly.


Applications and Outcomes of Internet of Things for Patients with Alzheimer's Disease/Dementia: A Scoping Review.
We aimed to identify and classify the Internet of Things (IoT) technologies used for Alzheimer's disease (AD)/dementia as well as the healthcare aspects addressed by these technologies and the outcomes of the IoT interventions. Methodology. We searched PubMed/MEDLINE, IEEE Explore, Web of Science, OVID, Scopus, Embase, Cochrane, and Google Scholar. In total, 13,005 papers were reviewed, 36 of which were finally selected. All the reviews were independently carried out by two researchers. In the case of any disagreement, the problem was resolved by holding a meeting and exchanging views. Due to the diversity of the reviewed studies, narrative analysis was performed. Among the technologies used for the patients including radio frequency identification (RFID), near field communication (NFC), ZigBee, Bluetooth, global positioning system (GPS), sensors, and cameras, the sensors were employed in 36 studies, most of which were switch and vital sign monitoring sensors. The most common aspects of AD/dementia care monitored using these technologies were activities of daily living (ADLs) in 27 studies, followed by sleep patterns and disease diagnosis in 19 and 14 studies, respectively. Sleeping, medication, vital signs, agitation, memory, social interaction, apathy, movement, tracking, and fall were other aspects monitored by IoT. Then, their outcomes were reported. Using IoT for AD/dementia provides many opportunities for considering various aspects of this disease. Moreover, the ability to use various technologies for gathering patient-related data provides a comprehensive application for almost all aspects of the patients' care with high accuracy.


Women's Lifestyle Physical Activity Program for African American Women: Fidelity Plan and Outcomes.
For interventions to be implemented effectively, fidelity must be documented. We evaluated fidelity delivery, receipt, and enactment of the 48-week Women's Lifestyle Physical Activity Program conducted to increase physical activity and maintain weight in African American women. Three study conditions all received 6 group meetings; 1 also received 11 motivational interviewing personal calls (PCs), 1 received11 automated motivational message calls (ACs), and 1 received no calls. Group meeting delivery was assessed for adherence and competence. PC delivery was assessed with the Motivational Interviewing Treatment Integrity Code. Receipt was defined as group meeting attendance, completion of PCs, and listening to ACs. Enactment was number of weeks an accelerometer was worn. For group meeting delivery, mean adherence was 80.8% and mean competence 2.9 of 3.0. Delivery of PCs did not reach criterion for competence. Receipt of more than one-half the dose was achieved for 84.9% of women for group meetings, 85.5% for PCs, and 42.1% for ACs. Higher group meeting attendance was associated with higher accelerometer steps at 24 weeks and lower BMI at 24 and 48 weeks. Fidelity measurement and examination of intervention delivery, receipt, and enactment are important to explicate conditions in which interventions are successful.


Mobile apps for real-world evidence in health care.
The use of real-world evidence for health care research and evaluation is growing. Mobile health apps have often-overlooked potential to contribute valuable real-world data that are not captured by other sources and could provide data that are more cost-effective and generalizable than can randomized controlled trials. However, there are several challenges that must be overcome to realize the potential value of patient-used mobile health app real-world data, including data quality, motivation for long-term use, privacy and security, methods of analysis, and standardization and integration. Addressing these challenges will increase the value of data from mobile health apps to inform real-world evidence and improve patient empowerment, clinical management, disease research, and treatment development.


Mercury and zinc differentially inhibit shark and human CFTR orthologues: involvement of shark cysteine 102.
The apical membrane is an important site of mercury toxicity in shark rectal gland tubular cells. We compared the effects of mercury and other thiol-reacting agents on shark CFTR (sCFTR) and human CFTR (hCFTR) chloride channels using two-electrode voltage clamping of cRNA microinjected Xenopus laevis oocytes. Chloride conductance was stimulated by perfusing with 10 microM forskolin (FOR) and 1 mM IBMX, and then thio-reactive species were added. In oocytes expressing sCFTR, FOR + IBMX mean stimulated Cl(-) conductance was inhibited 69% by 1 microM mercuric chloride and 78% by 5 microM mercuric chloride (IC(50) of 0.8 microM). Despite comparable stimulation of conductance, hCFTR was insensitive to 1 microM HgCl(2) and maximum inhibition was 15% at the highest concentration used (5 microM). Subsequent exposure to glutathione (GSH) did not reverse the inhibition of sCFTR by mercury, but dithiothreitol (DTT) completely reversed this inhibition. Zinc (50-200 microM) also reversibly inhibited sCFTR (40-75%) but did not significantly inhibit hCFTR. Similar inhibition of sCFTR but not hCFTR was observed with an organic mercurial, p-chloromercuriphenylsulfonic acid (pCMBS). The first membrane spanning domain (MSD1) of sCFTR contains two unique cysteines, C102 and C303. A chimeric construct replacing MSD1 of hCFTR with the corresponding sequence of sCFTR was highly sensitive to mercury. Site-specific mutations introducing the first but not the second shark unique cysteine in hCFTR MSD1 resulted in full sensitivity to mercury. These experiments demonstrate a profound difference in the sensitivity of shark vs. human CFTR to inhibition by three thiol-reactive substances, an effect that involves C102 in the shark orthologue.


Supported Palladium Nanoparticle-Catalyzed Carboxylation of Aryl Halides, Alkenylsilanes, and Organoboronic Acids Employing Oxalic Acid as the C1 Source.
Polystyrene-supported palladium(0) (Pd@PS) nanoparticles as a heterogeneous catalyst have been developed for caboxylation of aryl halides, alkenylsilanes, and organoboronic acids to produce the corresponding carboxylic acids with minor quantities of corresponding aldehydes using bench-stable and inexpensive oxalic acid as the C1 source under focused microwave irradiation. The close vicinity of oxalic acid to Pd@PS maintained through ionic bonding helped to produce CO2 over the catalytic surface that concurrently participated in the carboxylation reaction.


Small area analysis: abortion statistics.
Small area analysis has developed over the last two or three decades as a useful tool in health services research, as it allows the identification of areas within health or local authority districts with high rates of morbidity and mortality, and thus provides a useful base for planning the delivery of health services. A profile was compiled for Liverpool Family Health Services Authority on planned parenthood in the Liverpool District, with the aim of identifying where resources are needed most - which parts of the City, and which groups of women, are most in need. The profile included an analysis of various outcome measures, including abortion statistics, which can be used as a guide to the apparent effectiveness of services. Using a combination of statistics on NHS abortions for electoral wards, and private abortions by postal district, it became apparent that, on the whole, areas of high NHS induced abortion rates also have high private (British Pregnancy Advisory Service; BPAS) induced abortion rates, and vice versa. The maps for NHS and BPAS abortion rates suggest that total abortion rates are high in City centre wards, and low in areas south of the City. This would suggest that there are differences in social factors, family planning provision, and other factors which are influencing abortion rates. Although available indicators would suggest that City centre wards are in greatest need of improved family planning provision, these are the wards which are relatively well provided with health authority family planning clinics.(ABSTRACT TRUNCATED AT 250 WORDS)


Yersinia-specific antibodies in serum and synovial fluid in patients with Yersinia triggered reactive arthritis.
To further evaluate the role of bacterial antigens in triggering inflammation in the joint in patients with reactive arthritis by studying local antibody synthesis in the joint. Yersinia-specific antibodies in paired serum and synovial fluid samples from 29 patients with yersinia triggered reactive arthritis were studied using an enzyme linked immunosorbent assay (ELISA), an inhibition ELISA with six monoclonal antibodies against lipopolysaccharide or released proteins of yersinia and immunoblotting. Antibodies of IgM, IgG and IgA classes, as well as antibodies of IgA subclasses and those containing secretory component were measured against the lipopolysaccharide and the sodium dodecyl sulphate extract of whole Yersinia enterocolitica O:3 bacteria. It was shown that yersinia-specific antibodies, as well as antibodies against other microbial antigens (rubella, measles, Bordetella pertussis, tetanus toxoid and Candida albicans) in synovial fluid mirror those in serum by concentration, by specificity and by distribution in classes and subclasses. These results do not suggest any strong local antibody production, but indicate that the majority of yersinia antibodies in the synovial fluid are derived from the circulation.


Metagenomic Human Repiratory Air in a Hospital Environment.
Hospital-acquired infection (HAI) or nosocomial infection is an issue that frequent hospital environment. We believe conventional regulated Petri dish method is insufficient to evaluate HAI. To address this problem, metagenomic sequencing was applied to screen airborne microbes in four rooms of Beijing Hospital. With air-in amount of sampler being setup to one person's respiration quantity, metagenomic sequencing identified huge numbers of species in the rooms which had already qualified widely accepted petridish exposing standard, imposing urgency for new technology. Meanwhile,the comparative culture only got small portion of recovered species and remain blind for even cultivable pathogens reminded us the limitations of old technologies. To the best of our knowledge, the method demonstrated in this study could be broadly applied in hospital indoor environment for various monitoring activities as well as HAI study. It is also potential as a transmissible pathogen real-time modelling system worldwide.


Clinical outcomes of risk-based caries prevention in preschool-aged children.
The aim of this study was to evaluate outcomes in young children of risk-based management of dental caries in comparison with routine prevention. The study was carried out in two municipal health centers in Central Finland. The risk-based prevention group consisted of 299 children from Vanha Korpilahti, and the routine prevention group of 226 children from Saarijärvi. The children were 2 yr old at baseline, and they were followed up for 3 yr. All children received regular annual oral health care. In the risk-based prevention group, the presence of mutans streptococci (MS) in plaque (Dentocult-SM strip mutans -test, Orion Diagnostica, Espoo, Finland) and incipient caries lesions were the screening criteria. Additional prevention was targeted at MS-positive subjects twice a year, consisting of health education and application of fluoride varnish. For those who had incipient lesions, 'the high-risk category', additional prevention was given four times a year and this included also chlorhexidine varnish treatments. The screening and the preventive measures were successfully carried out by specially trained dental assistants. The proportion of children with cavitated caries or fillings was significantly lower in the risk-based than in the routine prevention group. The treatment effect was strongest within the high-risk category: two subjects had to be treated with intensive care for 3 yr to avoid restorative treatment of dental caries by the age of 5 yr in one subject (number needed to treat (NNT) = 2.0; 95% CI 1.4-3.8). The accuracy of screening was evaluated in the routine prevention group and found acceptable. The results indicate that in young children, risk-based management of caries seems practical, and prevention of caries can be targeted efficiently to individuals at risk.


Perception of voice-onset-time continua: a signal detection analysis.
An absolute identification task and various discrimination tasks were performed on synthetic syllables initiated by alveolar stops varying in voice-onset-time (VOT). Signal detection analyses of the data yielded three main findings. First, discrimination d's exceeded those for absolute identification. Greater instability of judgment in the latter than in the former task explained this difference. Second, stimuli within a phonetic category were discriminable, even in a delayed 2IAX paradigm with 4s between stimuli. Third, a category boundary effect appeared: identification and discrimination d's were largest around the voiced/voiceless boundary for alveolar stops. The relationship between discrimination and identification d's varies with response constraints, the number of just noticeable differences in the stimulus array, and stability of judgments in the various tasks. Nearly equal performance in discrimination and identification tasks is not a sufficient condition for a category boundary effect to occur. Several arguments are advanced against a dual-coding model. A continuous model which invokes only a single decision process may account more gracefully for the relationship between identification and discrimination of both consonants and vowels.


The association of clinical features and laboratory findings of COVID-19 infection with computed pneumonia volume.
Coronavirus disease 2019 (COVID-19) was first detected in China in December 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020.To study the clinical features of patients with COVID-19, we analyzed the correlation between some inflammation-related indicators in patients' serum and the severity of the disease, especially PV (pneumonia volume under CT scan) and pneumonia volume ratio (PVR).Sixty-six COVID-19 patients in Huai'an, China were selected as the research subjects. We collected the clinical data, including general characteristics, clinical symptoms, serum test results and CT performance, explored the relationship between inflammation-related indexes, oxygenation index, PV, PVR, while indicators of mild to moderate patients and severe patients were compared.The most prominent manifestations of COVID-19 patients were fever (47, 71.2%); cough (41, 62.1%), with or without respiratory and other systemic symptoms; There was no difference in gender (P = .567) and age (P = .865) between mild to moderate and severe groups. High sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6) of overall patients were higher than the normal range (P < .001, respectively). hs-CRP was negatively correlated with oxygenation index (OI) (r = -0.55), whereas positively correlated with PV, PVR and ESR (r = 0.89; r = 0.87; r = 0.47, respectively); ESR was negatively correlated with OI (r = -0.45), meanwhile it was positively correlated with PV and PVR (r = 0.44; r = 0.46, respectively). OI was negatively correlated with PV and PVR (r = -0.6, respectively). PV had a clear correlation with PVR (r = 1). Severe patients' hs-CRP, PV, PVR were higher than mild to moderate group (P = .006; P = .001; P < .001, respectively), but OI was lower (P < .001).The clinical features of COVID-19 were similar to general viral pneumonia. hs-CRP, ESR showed a certain correlation with the PV and PVR, which might play a certain role in assessing the severity of COVID-19.


[Transitional cell carcinoma in prostate after intravesical instillation of Bacillus Calmette-Guerin].
We report 3 cases of prostatic involvement of transitional cell carcinomas (TCCs). All cases presented positive urinary cytology after intravesical instillation of Bacillus Calmette-Guerin (BCG) and then random biopsy of bladder and transurethral resection (TUR)-biopsy of prostatic urethra were performed. TUR-biopsy demonstrated TCC in the prostate, although random biopsy failed to detect tumors in the bladder in all cases. Case 1 was treated with cystourethrectomy with ileal conduit, case 2 was treated with cystourethrectomy with bilateral ureterocutaneostomy and case 3 was treated with cystectomy with orthotopic ileal neobladder reconstruction. All cases are alive with no evidence of disease. TUR-biopsy of prostatic urethra should be perfomed when patients present positive urinary cytology after BCG instillation therapy, because prostatic involvement of TCC associated with bladder carcinoma in situ is not rare.


The Incidence of Acute Kidney Injury (AKI) in Critically Ill COVID-19 Patients: A Single-Center Retrospective Cohort Study at a Tertiary Level Hospital in Oman.
Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. Coronavirus disease 2019 (COVID-19) affects the renal system frequently and leads to AKI. This study aims to determine the incidence of AKI, risk factors including hyperglycemia, and the requirement for renal dialysis. A retrospectively observational study was done at Sultan Qaboos University Hospital between March 2020 and September 2021. A total of 286 adult patients with laboratory-confirmed COVID-19 infection admitted to the intensive care unit (ICU) were included in the study. The patient's medical records were reviewed. Patients' baseline demographic characteristics, APACHE score on admission, clinical data including length of stay, oxygenation parameters, ventilator days, shock, AKI (KIDIGO guideline), dialysis, medications, lab on admission as well as during the ICU stay, and the outcome (mortality) were recorded in detail. Follow-up was done till discharge from ICU. The study population included 68.5% (196/286) males. The median age was 56 years (interquartile range, IQR: 43-66.25). The incidence of AKI was 55.2% (158/286) overall. Out of those who had AKI, 27.2% (43/158), 31.6% (50/158), and 41.1% (65/158) developed AKI stages 1, 2, and 3, respectively. Univariate analysis for the development of AKI showed the following significant variables: age (p=0.005; odds ratio, OR 1.024; 95% confidence interval, CI 1.007-1.041), creatinine level on admission (p=0.012; OR 1.005; 95%CI 1.001-1.008), APACHE score on admission (p<0.001; OR 1.049; 95%CI 1.021-1.077), P/F ratio (p<0.001; OR 0.991; 95%CI 0.987-0.995), nephrotoxic agent (p<0.001; OR 8.556; 95%CI 4.733-15.467), shock (p<0.001; OR 8.690; 95%CI 5.087-14.843), days on the ventilator (p<0.001; OR 1.085; 95%CI 1.043-1.129), and length of stay in ICU (p<0.001; OR 1.082; 95%CI 1.047-1.119). The multivariate analysis confirmed only shock (p=0.004; OR 5.893; 95%CI 1.766-19.664). A total of 41.7% (66/158) of patients received dialysis. Hyperglycemia was not associated with the development of AKI. For patients with AKI, those having high APACHE score (p<0.001), shock (p=0.56; OR 2.326; 95%CI 1.036-5.223), ischemic heart disease (IHD) (p=0.002; OR 9.000; 95%CI 1.923-42.130), and hypertension (p=0.023; OR 2.145; 95%CI 11.125-4.090) were significantly associated with the requirement of dialysis. The mortality was found to be 59.1% (169/286) overall whereas it was 83.5% (132/158) for AKI versus 28.9% (37/158) for non-AKI cases. A high incidence of AKI for critically ill COVID-19 cases was found in this study. The shock was the only significant predictor for the development of AKI. AKI is associated with high mortality in these patients.


Increasing fluid intake and reducing dehydration risk in older people living in long-term care: a systematic review.
To assess the efficacy of interventions and environmental factors on increasing fluid intake or reducing dehydration risk in older people living in long-term care facilities. Systematic review of intervention and observational studies. Thirteen electronic databases were searched from inception until September 2013 in all languages. References of included papers and reviews were checked. Intervention and observational studies investigating modifiable factors to increase fluid intake and/or reduce dehydration risk in older people (≥65 years) living in long-term care facilities who could drink orally. Two reviewers independently screened, selected, abstracted data, and assessed risk of bias from included studies; narrative synthesis was performed. A total of 4328 titles and abstracts were identified, 325 full-text articles were obtained and 23 were included in the review. Nineteen intervention and 4 observational studies from 7 countries investigated factors at the resident, institutional, or policy level. Overall, the studies were at high risk of bias due to selection and attrition bias and lack of valid outcome measures of fluid intake and dehydration assessment. Reported findings from 6 of the 9 intervention studies investigating the effect of multicomponent strategies on fluid intake or dehydration described a positive effect. Components included greater choice and availability of beverages, increased staff awareness, and increased staff assistance with drinking and toileting. Implementation of the US Resident Assessment Instrument reduced dehydration prevalence from 3% to 1%, P = .01. Two smaller studies reported positive effects: one on fluid intake in 9 men with Alzheimer disease using high-contrast red cups, the other involved supplementing 13 mildly dehydrated residents with oral hydration solution over 5 days to reduce dehydration. Modifications to the dining environment, advice to residents, presentation of beverages, and mode of delivery (straw vs beaker; prethickened drinks vs those thickened at the bedside) were inconclusive. Two large observational studies with good internal validity investigated effects of ownership; in Canada, for-profit ownership was associated with increased hospital admissions for dehydration; no difference was seen in dehydration prevalence between US for-profit and not-for-profit homes, although chain facilities were associated with lower odds of dehydration. This US study did not suggest any effect of staffing levels on dehydration prevalence. A wide range of interventions and exposures were identified, but the efficacy of many strategies remains unproven due to the high risk of bias present in many studies. Reducing dehydration prevalence in long-term care facilities is likely to require multiple strategies involving policymakers, management, and care staff, but these require further investigation using more robust study methodologies. The review protocol was registered with the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42012003100).


Macroporous scaffolds associated with cells to construct a hybrid biomaterial for bone tissue engineering.
Bone tissue has the ability to heal without a scar and to remodel, which promotes three basic functions: locomotion, protection of internal organs and mineral homeostasis. Although bone regeneration is highly efficient, some clinical situations - such as large bone defects - require specific treatments in order to promote bone healing. Allogenic or autologous bone grafts have been used in these procedures with limited success and, based on this, bone tissue-engineering approaches have been investigated extensively. Tissue engineering has been defined as the application of principles and techniques of the life sciences and engineering to the design, modification and growth of living tissues using biomaterials, cells and growth factors, alone or in combination. The association of cells with porous scaffolds to produce 3D hybrid osteogenic constructs is a common subject in bone tissue-engineering research and will be the focus of this review. We will present some aspects of bone biology, the cells and scaffolds used to engineer bone, and techniques to fabricate the hybrid biomaterial.


Electrospun biomaterial scaffolds with varied topographies for neuronal differentiation of human-induced pluripotent stem cells.
In this study, we investigated the effect of micro and nanoscale scaffold topography on promoting neuronal differentiation of human induced pluripotent stem cells (iPSCs) and directing the resulting neuronal outgrowth in an organized manner. We used melt electrospinning to fabricate poly (ε-caprolactone) (PCL) scaffolds with loop mesh and biaxial aligned microscale topographies. Biaxial aligned microscale scaffolds were further functionalized with retinoic acid releasing PCL nanofibers using solution electrospinning. These scaffolds were then seeded with neural progenitors derived from human iPSCs. We found that smaller diameter loop mesh scaffolds (43.7 ± 3.9 µm) induced higher expression of the neural markers Nestin and Pax6 compared to thicker diameter loop mesh scaffolds (85 ± 4 µm). The loop mesh and biaxial aligned scaffolds guided the neurite outgrowth of human iPSCs along the topographical features with the maximum neurite length of these cells being longer on the biaxial aligned scaffolds. Finally, our novel bimodal scaffolds also supported the neuronal differentiation of human iPSCs as they presented both physical and chemical cues to these cells, encouraging their differentiation. These results give insight into how physical and chemical cues can be used to engineer neural tissue.


[Primary hyperparathyroidism. History].
The term primary hyperparathyroidism currently refers to the clinical and biological manifestations resulting from the hypersecretion of parathyroid hormone by one or several parathyroid adenomas. This entity is a recent one since it goes back to 1925. The clinical picture resulting from this anomaly, were first described as Recklinghausen's fibrous osteitis, which was not justified since Recklinghausen had not established the relationship between the clinical manifestations and the adenoma discovered by Mandl, then under the name of parathyroid osteosis. This term was justified at a time when the disease presented only bony manifestations with biological evidence. Primary hyperthyroidism is the current appellation, demonstrating that the disease is now a biological disease, often discovered systematically, with therapeutic progress, progress in biological identification and possibility of medical forms without mandatory surgical outcome. Bibliographic references accompany the various stages of this historical reminder.


[Clinical features and ABCC2 genotypic analysis of an infant with Dubin-Johnson syndrome].
Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder resulting from biallelic mutations of ABCC2 gene, with long-term or intermittent conjugated hyperbilirubinemia being the main clinical manifestation. This paper aims to report the clinical features and ABCC2 genotypes of an infant with DJS. A 9.5-month-old male infant was referred to the hospital due to abnormal liver function discovered over 9 months. The major clinical presentation was prolonged jaundice since neonatal period. A series of biochemistry analysis revealed markedly elevated total bilirubin, conjugated bilirubin and total bile acids. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. Physical examination revealed jaundiced skin and sclera, and a palpable liver 3 cm below the right subcostal margin with medium texture. The spleen was not enlarged. Genetic analysis revealed a splice-site variant c.3988-2A>T and a nonsense variant c.3825C>G (p.Y1275X) in the ABCC2 gene of the infant, which were inherited from his mother and father respectively. The former had not been previously reported. Then ursodeoxycholic acid and phenobarbital were given orally. Half a month later, as a result, his jaundice disappeared and the biochemistry indices improved. However, the long-term outcome needs to be observed. Literature review revealed that neonates/infants with DJS presented with cholestatic jaundice soon after birth as the major clinical feature, and the ABCC2 variants exhibited marked heterogeneity.


Postoperative complications in patients with cochlear implants and impacts of nursing intervention.
This study shows that cochlear implantation is relatively safe surgery with few major complications and within acceptable limits. However, close follow-up observation and effective medical and nursing intervention could alleviate further complications and thus become key elements for promoting recovery of patients undergoing such surgery. Cochlear implantation has become an effective method for curing patients disabled by profound hearing loss in China. However, full exploration of the associated complications remains to be completed. The objective of this study was thus to analyse the postoperative complications in patients with cochlear implants (CIs) in order to design improved measures for clinical and nursing interventions. A retrospective study of 262 patients receiving CIs at the Department of Otorhinolaryngology/Head and Neck Surgery, Chinese People's Liberation Army General Hospital, Beijing, China from March 1997 to December 2006 was conducted. Among 262 patients, 4 cases (1.5%) had 1 or more major complications requiring substantial medical or nursing interventions, including 1 case of cerebrospinal fluid (CSF) otorrhoea accompanied by meningitis, 2 cases of facial nerve paresis and 1 case of perforation of tympanic membrane. Forty cases (15.3%) had some form of minor complication that settled spontaneously or easily with conventional treatments and nursing, of which dizziness and vomiting was the most frequent (4.2%), followed by CSF gusher without otorrhoea and/or induced meningitis (2.7%), tinnitus (1.9%) and facial nerve partially exposed without paralysis (1.5%). Eleven cases (4.2%) had some symptoms associated with installation of the cochlear device. Except for one patient who had no response after implantation because his auditory nerves were underdeveloped, all the patients who received appropriate treatment and nursing intervention had a favourable prognosis.


Multiple contextual control over non-arbitrary relational responding and a preliminary model of pragmatic verbal analysis.
The aims of the current study were (i) to explore the flexibility and generalizability of non-arbitrary relational contextual control in human participants and (ii) to provide a simple empirical model of pragmatic verbal analysis, a key element in the relational frame theory approach to problem solving. Participants were trained to respond to abstract shapes as cues for responding in accordance with non-arbitrary relations of sameness, difference and opposition. Next, sameness, difference and opposition relational responding was brought under additional contextual control by arbitrary B1-B3 stimuli, such that, depending on the B stimulus presented, relational responding was applied to one of three distinct physical dimensions of multidimensional shapes. Equivalence training and testing was then provided such that participants showed derived relations between the B stimuli and three novel arbitrary C stimuli. Two additional cues were then trained such that they occasioned comparative (more/less) relations. A final test showed that the C stimuli exerted contextual control over physical dimensions in the novel context of more/less/same non-arbitrary relational responding. These findings provide a simple, preliminary model of pragmatic verbal analysis.


Association between TAp73, p53 and VASH1 expression in lung adenocarcinoma.
TAp73 and p53 are involved in regulating tumor angiogenesis and vasohibin-1 (VASH1) is an anti-angiogenic factor. Whether TAp73 regulates angiogenesis positively or negatively is controversial. The status of P53 may determine the effect of TAp73 on angiogenesis. To the best of our knowledge it has not been previously reported whether TAp73, p53 and VASH1 are coexpressed in lung cancer. We profiled the association between TAp73 and p53 and VASH1 expression in lung adenocarcinoma (LAC) and investigated the function of TAp73 in regulating tumor angiogenesis. TAp73, p53 and VASH1 expression in 53 human LAC tissues and the adjacent normal tissues were evaluated using immunohistochemistry. The positive expression rates of p53, TAp73 and VASH1 were significantly higher (92.6, 97.7 and 67.4%, respectively) in LAC tissue compared with paraneoplastic lung tissue (7.4, 2.3 and 32.6%, respectively, P<0.01). Pearson's correlation coefficient showed a significant positive correlation between p53 and TAp73 (r=0.474, P<0.01) and TAp73α and VASH1 (r=0.367, P<0.01). The positive expression rate of p53 and VASH1 was almost significantly correlated (r=0.187, P=0.055). Similarly, p53 expression intensity had a significant positive correlation with TAp73α (r=0.517, P<0.01) and with VASH1 (r=0.277, P<0.01), as did TAp73α with VASH1 (r=0.351, P<0.01). TAp73, p53 (mutant) and VASH1 expression was significantly higher in LAC tissue compared with paraneoplastic lung tissue. The expression trends of the three proteins were significantly positively correlated with each other in LAC. These results suggest that TAp73 may suppress tumor angiogenesis in LAC.


IL-1beta-induced production of metalloproteinases by synovial cells depends on gap junction conductance.
Synovial cells can form networks connected by gap junctions. The purpose of this study was to obtain evidence for a necessary role of gap junction intercellular communication in protein secretion by synovial cells. We developed a novel assay to measure the enzymatic activity of metalloproteinases (MMPs) produced by synovial cells in response to interleukin-1beta (IL-1beta) and employed the assay to explore the biological function of gap junctions. IL-1beta produced a dose-dependent increase in MMP activity that was blocked by exposure to the gap junction inhibitors 18alpha-glycyrrhetinic acid and octanol for as few as 50 min. The inhibitors produced an immediate and marked reduction in intercellular communication, as assessed by transient current analysis using the nystatin perforated-patch method. These observations suggest that communication through gap junctions early in IL-1beta signal transduction is critical to the process of cytokine-regulated secretion of MMPs by synovial cells.


Intrathecal oxygen concentration as a new indicator of spinal cord ischemia.
A number of approaches have been put forward to monitor spinal cord ischemia during thoracic and thoracoabdominal aortic occlusion. However, none of these can ultimately prevent devastating complications which result from ischemic spinal cord injury. A direct measurement of the oxygen content of the spinal cord may accurately indicate the perfusion state, but in practice it is impractical. We surmised that intrathecal and/ or epidural oxygen concentration(I-pO2 and E-pO2, respectively) accurately reflect oxygen content in the spinal cord. So, we examined whether or not I-pO2 and/or E-pO2 correlated with the spinal cord pO2 (S-pO2) in dogs. In nine mongrel dogs, a model of graded spinal cord ischemia was developed by stepwise alternation of the level of aortic occlusion with an intraaortic balloon catheter. I-pO2, E-pO2 and S-pO2 were measured with a mass spectrometer. Our results show that, both I-pO2 and E-pO2 significantly correlated with S-pO2. I-pO2 correlated with S-pO2 better than E-pO2 did. Therefore, I-pO2 can be used as a new indicator for spinal cord ischemia, and I-pO2 monitoring would be useful to prevent paraplegia associated with thoracic aortic surgery.


Audiological profile in older children and adolescents with unrepaired cleft palate.
To study the audiological profile in the cleft population comprising older children and adolescents with unrepaired cleft palate and to arrive at a consensus regarding management of otitis media with effusion in this unique group. Tertiary care institute in Chandigarh, Punjab, India. Prospective study based on all patients older than 7 years with unrepaired cleft palate, attending the plastic surgery outpatient department, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, Punjab, India, from January 2001 to December 2002. Patients with submucous cleft were excluded from the study. General characteristics, otoscopic findings, pure tone audiometry, and impedence audiometry of all patients were recorded. Patients' ages ranged from 8 to 18 years, with a mean of 10.5 years. Regarding otological complaints, 86.7% were asymptomatic. Otoscopic findings revealed mild retraction as the most common finding in 50% of the ears. Type B curve was the most common tympanometric finding. The highest and lowest hearing thresholds recorded were 45 db and 15 db, respectively, with a mean of 27.11 db. The audiological profile of this unique group, which neither had undergone palatoplasty nor had received treatment for the ear condition, demonstrates a mild to moderate hearing impairment. This definitely requires treatment, but owing to the lack of a prospective control group, it is difficult to conclude whether these patients are benefited by conservative treatment alone or by an early aggressive surgical treatment for otitis media with effusion (OME).


Comparison of 3 Different Minimally Invasive Surgical Techniques for Lumbar Spinal Stenosis: A Randomized Clinical Trial.
Operations for lumbar spinal stenosis is the most often performed surgical procedure in the adult lumbar spine. This study reports the clinical outcome of the 3 most commonly used minimally invasive posterior decompression techniques. To compare the effectiveness of 3 minimally invasive posterior decompression techniques for lumbar spinal stenosis. This randomized clinical trial used a parallel group design and included patients with symptomatic and radiologically verified lumbar spinal stenosis without degenerative spondylolisthesis. Patients were enrolled between February 2014 and October 2018 at the orthopedic and neurosurgical departments of 16 Norwegian public hospitals. Statistical analysis was performed in the period from May to June 2021. Patients were randomized to undergo 1 of the 3 minimally invasive posterior decompression techniques: unilateral laminotomy with crossover, bilateral laminotomy, and spinous process osteotomy. Primary outcome was change in disability measured with Oswestry Disability Index (ODI; range 0-100), presented as mean change from baseline to 2-year follow-up and proportions of patients classified as success (>30% reduction in ODI). Secondary outcomes were mean change in quality of life, disease-specific symptom severity measured with Zurich Claudication Questionnaire (ZCQ), back pain and leg pain on a 10-point numeric rating score (NRS), patient perceived benefit of the surgical procedure, duration of the surgical procedure, blood loss, perioperative complications, number of reoperations, and length of hospital stay. In total, 437 patients were included with a median (IQR) age of 68 (62-73) years and 230 men (53%). Of the included patients, 146 were randomized to unilateral laminotomy with crossover, 142 to bilateral laminotomy, and 149 to spinous process osteotomy. The unilateral laminotomy with crossover group had a mean change of -17.9 ODI points (95% CI, -20.8 to -14.9), the bilateral laminotomy group had a mean change of -19.7 ODI points (95% CI, -22.7 to -16.8), and the spinous process osteotomy group had a mean change of -19.9 ODI points (95% CI, -22.8 to -17.0). There were no significant differences in primary or secondary outcomes among the 3 surgical procedures, except a longer duration of the surgical procedure in the bilateral laminotomy group. No differences in clinical outcomes or complication rates were found among the 3 minimally invasive posterior decompression techniques used to treat patients with lumbar spinal stenosis. ClinicalTrials.gov Identifier: NCT02007083.


Approximate entropy of network parameters.
We study the notion of approximate entropy within the framework of network theory. Approximate entropy is an uncertainty measure originally proposed in the context of dynamical systems and time series. We first define a purely structural entropy obtained by computing the approximate entropy of the so-called slide sequence. This is a surrogate of the degree sequence and it is suggested by the frequency partition of a graph. We examine this quantity for standard scale-free and Erdös-Rényi networks. By using classical results of Pincus, we show that our entropy measure often converges with network size to a certain binary Shannon entropy. As a second step, with specific attention to networks generated by dynamical processes, we investigate approximate entropy of horizontal visibility graphs. Visibility graphs allow us to naturally associate with a network the notion of temporal correlations, therefore providing the measure a dynamical garment. We show that approximate entropy distinguishes visibility graphs generated by processes with different complexity. The result probes to a greater extent these networks for the study of dynamical systems. Applications to certain biological data arising in cancer genomics are finally considered in the light of both approaches.


Sp1 promotes cell migration and invasion in oral squamous cell carcinoma by upregulating Annexin A2 transcription.
Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastatic potential in head and neck. Revealing the mechanism of OSCC metastasis will benefit the prognosis and prevention of OSCC. Sp1 is a transcription factor involved in the progression of several tumors. Annexin A2 functions as an oncogene, and there are three putative Sp1 binding sites in the Annexin A2 promoter region. Therefore, we hypothesized that Sp1 could regulate OSCC metastasis by regulating Annexin A2 expression. Quantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate Sp1 or Annexin A2 expression. Transwell assays were used to evaluate the migration and invasion capacity of OSCC cells. Luciferase assays and Chromatin immunoprecipitation assays were used to verify whether Sp1 regulate Annexin A2 at the transcriptional level. We found that the expression of Sp1 increased in OSCC tissues compared to paired adjacent normal tissues, and the overexpression of Sp1 was associated with tumor metastasis. Furthermore, Sp1 promoted cell migration and invasion through Annexin A2. In addition, we verified that Sp1 controls Annexin A2 expression at the transcriptional level and identified the binding sites involved. Our study suggests that Sp1/Annexin A2 expression could be a promising prognostic biomarker and therapeutic target for OSCC metastasis.


Estimation of lithium clearance from routine clinical data in Egyptian bipolar patients. A population pharmacokinetic approach.
Population pharmacokinetics (PK) of lithium as a mood stabilizer was investigated in Egyptian patients with bipolar affective disorders (n = 50) of whom 31 were suffering from lithium toxicity. The mean (+/- SD) age and body weight of patients were 33 +/- 10 years and 67 +/- 3.6 kg, respectively. Patients selected were maintained on lithium carbonate controlled release tablets at doses of 400 mg/12 hours (n = 43) or 200 mg/12 hours (n = 7) respectively. In 19 patients who continued lithium therapy, 1 blood sample/patient was withdrawn for lithium level determination before the morning dose of the drug was given while for 31 patients who suffered from lithium-related toxicity and cessation of drug intake was therapeutically decided, a single blood was drawn at variable time (36, 48 or 72 h) following the last administered dose of the drug. The data was subjected to population PK analysis using NONMEM and a two-compartment model was used. Due to single point sparse data, not all parameters and their between subject variability (BSV) could be determined. Therefore, lithium clearance (CL) and BSV were estimated while other PK parameters were fixed using available literature information. First order (FO) estimation method was used in the analysis. Covariates were evaluated by univariate analysis using likelihood ratio test. The most significant covariate on lithium CL was found to be creatinine clearance (CrCL). The population CL of lithium in the final model was expressed as CLpop = 0.51 x (CrCL/105.3)0.44. The final population PK parameters estimates of lithium were: CL = 0.51 l/h with 12.7% BSV, V1 (Fixed) = 15.2 l, Q (Fixed) = 7.44 l/h, and V2 (Fixed) = 6.7 l. The mean value of lithium concentration at 12 hours as predicted by the final model in the patients with drug toxicity was 1.3 +/- 0.1 mmol/l versus 0.8 +/- 0.14 mmol/l in patients without toxic signs. External validation of the final model on another group of adult bipolar patients (n = 12) maintained on lithium therapy showed a predictive ability of -35 to 65% as represented by% error for the predictions.


Phospholipid-binding sites of phosphatase and tensin homolog (PTEN): exploring the mechanism of phosphatidylinositol 4,5-bisphosphate activation.
The lipid phosphatase activity of the tumor suppressor phosphatase and tensin homolog (PTEN) is enhanced by the presence of its biological product, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). This enhancement is suggested to occur via the product binding to the N-terminal region of the protein. PTEN effects on short-chain phosphoinositide (31)P linewidths and on the full field dependence of the spin-lattice relaxation rate (measured by high resolution field cycling (31)P NMR using spin-labeled protein) are combined with enzyme kinetics with the same short-chain phospholipids to characterize where PI(4,5)P2 binds on the protein. The results are used to model a discrete site for a PI(4,5)P2 molecule close to, but distinct from, the active site of PTEN. This PI(4,5)P2 site uses Arg-47 and Lys-13 as phosphate ligands, explaining why PTEN R47G and K13E can no longer be activated by that phosphoinositide. Placing a PI(4,5)P2 near the substrate site allows for proper orientation of the enzyme on interfaces and should facilitate processive catalysis.


Laboratory strength of glass ionomer and zinc phosphate cements.
The present in vitro study examined 3 mechanical properties, namely compressive, flexural, and diametral tensile strength, of various commercially available cements and core materials as a function of time after mixing. The examined materials were 2 cermet cements (Ketac Silver [ESPE, Seefeld, Germany] and Chelon Silver [ESPE]), 1 metal-reinforced glass ionomer cement (Miracle Mix [GC Dental Industrial Corp, Tokyo, Japan]), 2 conventional glass ionomer cements (Ketac Bond [ESPE] and Ketac Cem [ESPE]), 1 standard cure zinc phosphate cement (Harvard Cement [Richter and Hoffmann, Berlin, Germany]), and 1 zinc phosphate cement with the addition of 30% silver amalgam alloy powder (Harvard Cement 70% with Dispersalloy 30% [Richter and Hoffmann/Johnson and Johnson, East Windsor, NJ]). Properties were measured using a universal testing machine at 15 minutes, 1 hour, and 24 hours after first mixing. Compressive strengths varied widely between the 3 times of measurement from 5.8 +/- 6.6 MPa for Ketac Cem to 144.3 +/- 10.2 MPa for Ketac Silver. Twenty-four hours after mixing, the Bonferroni test showed significant (p <or= .01) differences between Ketac Silver and all other materials tested. Diametral tensile strengths ranged widely from 4.4 +/- 0.9 MPa for Ketac Cem to 11.5 +/- 2.2 MPa for Chelon Silver. At 15 minutes, 1 hour, and 24 hours after first mixing, the analysis of variance did not show any significant differences between Ketac Silver, Chelon Silver, and Miracle Mix. The 3-point flexural strength of Ketac Silver showed, at 15 minutes with 13.5 +/- 3.9 MPa and at 24 hours with 27.2 +/- 7.4 MPa, the highest values. Setting time influences the mechanical properties of the materials tested in this study. Ketac Silver, a glass ionomer cement reinforced with sintered glass-silver particles, showed the highest mechanical properties of the examined materials.


Neural Networks Trained via Reinforcement Learning Stabilize Walking of a Three-Dimensional Biped Model With Exoskeleton Applications.
Our group is developing a cyber-physical walking system (CPWS) for people paralyzed by spinal cord injuries (SCI). The current CPWS consists of a functional neuromuscular stimulation (FNS) system and a powered lower-limb exoskeleton for walking with leg movements in the sagittal plane. We are developing neural control systems that learn to assist the user of this CPWS to walk with stability. In a previous publication (Liu et al., Biomimetics, 2019, 4, 28), we showed a neural controller that stabilized a simulated biped in the sagittal plane. We are considering adding degrees of freedom to the CPWS to allow more natural walking movements and improved stability. Thus, in this paper, we present a new neural network enhanced control system that stabilizes a three-dimensional simulated biped model of a human wearing an exoskeleton. Results show that it stabilizes human/exoskeleton models and is robust to impact disturbances. The simulated biped walks at a steady pace in a range of typical human ambulatory speeds from 0.7 to 1.3 m/s, follows waypoints at a precision of 0.3 m, remains stable, and continues walking forward despite impact disturbances and adapts its speed to compensate for persistent external disturbances. Furthermore, the neural network controller stabilizes human models of different statures from 1.4 to 2.2 m tall without any changes to the control parameters. Please see videos at the following link: 3D biped walking control.


Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan.
Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy ( CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan. This prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two-pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed. Of the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5%) included, 1705 (86.5%) had ischemic stroke and 265 (13.5%) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8% (95% confidence interval [CI] = 2.1-3.5%). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6%), followed by intracerebral hemorrhage (5.3%), and infarct of undetermined etiology (2.7%), and was low in patients with cardioembolism (0.8%) and large artery atherosclerosis (0.7%). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95% CI = 1.67-12.14 in ischemic stroke; OR = 6.03, 95% CI = 1.03-35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95% CI, 1.26-12.92) were significantly associated with p.R544C. p.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.


Importance of a diffusion-dominant small volume to activate cell-secreted soluble factor signaling in embryonic stem cell culture in microbioreactors: a mathematical model based study.
In our previous studies, we observed that cell-secreted BMP4 had a prominent influence on mouse embryonic stem cell (mESC) behaviors in a membrane-based two-chambered microbioreactor (MB), but not in a macro-scale culture (6-well plate/6WP). In this study, we investigated how the physical aspects of these cultures regulated BMP4 signaling by developing mathematical models of the cultures. The models estimated signaling activity in the cultures by considering size of the undifferentiated mESC colonies and their growth, diffusion of BMP4, and BMP4 trafficking process in the colonies. The models successfully depicted measured profile of BMP4 concentration in the culture medium which was two times higher in the MB than that in the 6WP during 5-day culture. The models estimated that, owing to the small volume and the membrane, cells were exposed to a higher BMP4 concentration in the top chamber of the MB than that in the 6WP culture. The higher concentration of BMP4 induced a higher concentration of BMP4-bound receptor in the colony in the MB than in the 6WP, thereby leading to the higher activation of BMP4 signaling in the MB. The models also predicted that the size of the MB, but not that of the 6WP, was suitable for maximizing BMP4 accumulation and upregulating its signaling. This study will be helpful in analyzing culture systems, designing microfluidic devices for controlling ESC or other cell behavior.


Impact of Neoadjuvant Chemoradiation on Pathologic Response in Patients With Localized Pancreatic Cancer.
Introduction/Background: Multimodal neoadjuvant therapy has resulted in increased rates of histologic response in pancreatic tumors and adjacent lymph nodes. The biologic significance of the collective response in the primary tumor and lymph nodes is not understood. Methods: Patients with localized PC who received neoadjuvant therapy and surgery with histologic assessment of the primary tumor and local-regional lymph nodes were included. Histopathologic response was classified using the modified Ryan score as follows: no viable cancer cells (CR), rare groups of cancer cells (nCR), residual cancer with evident tumor regression (PR), and extensive residual cancer with no evident tumor regression (NR). Nodal status was defined by number of lymph nodes (LN) with tumor metastases: N0 (0 LN), N1 (1-3), N2 (≥4). Results: Of 341 patients with localized PC who received neoadjuvant therapy and surgery, 107 (31%) received chemoradiation alone, 44 (13%) received chemotherapy alone, and 190 (56%) received chemotherapy and chemoradiation. Histopathologic response consisted of 15 (4%) CRs, 59 (17%) nCRs, 188 (55%) PRs, and 79 (23%) NRs. Patients who received chemotherapy alone had the worst responses (n = 21 for NR, 48%) as compared to patients who received chemoradiation alone (n = 25 for NR, 24%) or patients who received both therapies (n = 33 for NR, 17%) (Table 1; p = 0.001). Median overall survival for all 341 patients was 39 months; OS by histopathologic subtype was not reached (CR), 49 months (nCR), 38 months (PR), and 34 months (NR), respectively (p = 0.004). Of the 341 patients, 208 (61%) had N0 disease, 97 (28%) had N1 disease, and 36 (11%) had N2 disease. In an adjusted hazards model, modified Ryan score of PR or NR (HR: 1.71; 95% CI: 1.15-2.54; p = 0.008) and N1 (HR: 1.42; 95% CI: 1.1.02-2.01; p = 0.04), or N2 disease (HR: 2.54, 95% CI: 1.64-3.93; p < 0.001) were associated with increased risk of death. Conclusions: Neoadjuvant chemotherapy alone is associated with lower rates of pathologic response. Patients with CR or nCR have a significantly improved OS as compared to patients with PR or NR. Nodal status is the most important pathologic prognostic factor. Neoadjuvant chemoradiation may be an important driver of pathologic response.


Novel 4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines as Delta(8)-Delta(7) sterol isomerase (emopamil binding protein) selective ligands with antiproliferative activity.
To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines was developed. Radioreceptor binding assays evidenced cis-19, cis-30 and cis-33 as new ligands with nanomolar affinity toward EBP site and a good selectivity relative to EBP-related sigma receptors. The most selective 2,6-dimethoxy derivative (cis-33) demonstrated the highest potency (EC(50) = 12.9 microM) and efficacy (70%) in inhibiting proliferation of human prostate cancer PC-3 cell line. Among the reference compounds, sigma(2) agonist 36 (PB28) reached the maximum efficacy (100%), suggesting the contribution of the sigma(2) receptor to the antiproliferative activity. This novel class of EBP inhibitors represents a valuable tool for investigating the last steps of cholesterol biosynthesis and related pathologies, as well as a starting point for developing new anticancer drugs.


Strains of the Morphospecies Ploeotia costata (Euglenozoa) Isolated from the Western North Pacific (Taiwan) Reveal Substantial Genetic Differences.
Two phagotrophic euglenid strains (Strains Pac and Tam) were isolated from coastal locations in Taiwan. Ultrastructural characteristics of the strains included five pellicle strips joined at the posterior end. The strips were formed by major grooves with bifurcated edges. At the cell anterior, the feeding structure formed a lip. Underneath the lip was a comb composed of layers of microtubules. Farther back, two supporting rods tapered toward the posterior end, and a number of vanes with attached microtubules were present between the rods. The morphological characteristics agree with Ploeotia costata Strain CCAP 1265/1. However, the 18S rDNA sequences of Strains Pac/Tam lacked a group I intron and possessed three extra insertions of 116, 67, and 53 bp. Phylogenetic analysis indicated low sequence similarity between Strains Pac/Tam and CCAP 1265/1 (92%). The morphospecies P. costata apparently includes a substantial level of DNA sequence divergence, and likely represents multiple molecular species units.


Preterm Children Born Small for Gestational Age are at Risk for Low Adult Bone Mass.
Cross-sectional studies suggest that premature birth and low birth weight may both be associated with low peak bone mass. We followed bone traits in preterm individuals and controls for 27 years and examined the effects of birth weight relative to gestational age [stratified as small for gestational age (SGA) or appropriate for gestational (AGA)] on adult bone mineral density (BMD). We measured distal forearm BMC (g/cm) and BMD (g/cm(2)) with single-photon absorptiometry (SPA) in 46 preterm children (31 AGA and 15 SGA) at mean age 10.1 years (range 4-16) and in 84 healthy age-matched children. The measurements were repeated 27 years later with the same SPA apparatus but then also with dual energy absorptiometry and peripheral computed tomography (pQCT). Preterm individuals were shorter (p = 0.03) in adulthood than controls. Preterm AGA individuals had similar BMC and BMD height-adjusted Z-scores in adulthood compared to controls. Preterm SGA individuals had lower distal forearm BMC and BMD height-adjusted Z-scores in adulthood than both controls and preterm AGA individuals. Preterm SGA individuals had lower gain from childhood to adulthood in distal forearm BMC height-adjusted Z-scores than controls (p = 0.03). The deficits in preterm SGA individuals in adulthood were also captured by DEXA in height-adjusted femoral neck (FN) BMC Z-score and height-adjusted FN BMD Z-score and by pQCT in tibial cross-sectional area (CSA) Z-score and stress strain index (SSI) Z-score, where all measurements were lower than controls (all p values <0.05). Preterm SGA individuals are at increased risk of reaching low adult bone mass, at least partly due to a deficit in the accrual of bone mineral during growth. In our cohort, we were unable to find a similar risk in preterm AGA individuals.


Time course of changes in ventricular fibrillation threshold in myocardial infarction: characteristics of acute and slow occlusion with respect to the collateral vessels of the heart.
The time course of the changes in ventricular fibrillation threshold (VFT) was determined in 28 dogs by means of electrical stimulation, triggered from the R wave, with DC square wave pulse series (of 140 ms duration) inserted into the vulnerable period of the cardiac cycle. After acute coronary occlusion there was a sudden decrease in the VFT followed by a slow increase such that 30 min after the ligation pre-occlusion values of VFT were reached. The magnitude of the decrease in VFT depended upon the collateral blood supply. There were no other changes in VFT during the remaining course of the experiment. Following slow coronary occlusion the first arrhythmic phase was not detectable. Any decreases in VFT that occurred were smaller and of shorter duration than those occurring after acute occlusion and were independent of the extent of the collateral blood supply.


[Pulmonary hamartoma: a case report].
The authors describe a case of lung hamartoma recently observed. Diagnosis occurred by chance through routine chest X-rays. A stationary radiological aspect of the hamartoma, regularly followed up, suggested to defer surgery up to the moment of a visible radiologic enlargement of the lesion.


Electron probe analysis of cementum surfaces.
The purpose of this study was to determine the presence of certain inorganic elements in various cementum surfaces. The electron probe analysis appears to be the most suitable technique for examining elemental composition within localized small areas of mineralized tissue, it was used to determine the mineral contents of nondiseased, periodontally diseased and root planing applied diseased cementum surfaces were determined by electron probe. Calcium (Ca) and phosphorus (P) were the elements searched for. Surface morphological features of these cementum surfaces were also examined. Electron probe analysis indicated an elevated Ca and P content in diseased cementum surfaces. Root planing of these surfaces did not reduce the mineral contents of these root surfaces. Our findings indicate that on the cementum surfaces affected by periodontal disease inorganic contents were altered and the hypermineralized layer in diseased cementum may play a role in preventing total diseased cementum removal by root planing.


Drug Discovery Testing Compounds in Patient Samples by Automated Flow Cytometry.
Functional ex vivo assays that predict a patient's clinical response to anticancer drugs for guiding cancer treatment have long been a goal, but few have yet proved to be reliable. To address this, we have developed an automated flow cytometry platform for drug screening that evaluates multiple endpoints with a robust data analysis system that can capture the complex mechanisms of action across different compounds. This system, called PharmaFlow, is used to test peripheral blood or bone marrow samples from patients diagnosed with hematological malignancies. Functional assays that use the whole sample, retaining all the microenvironmental components contained in the sample, offer an approach to ex vivo testing that may give results that are clinically relevant. This new approach can help to predict the patients' response to existing treatments or to drugs under development, for hematological malignancies or other tumors. In addition, relevant biomarkers can be identified that determine the patient's sensitivity, resistance, or toxicity to a given treatment. We propose that this approach, which better recapitulates the human microenvironment, constitutes a more predictive assay for personalized medicine and preclinical drug discovery.


Synergistic inhibition of Aβ production by combinations of γ-secretase modulators.
Alzheimer's disease is associated with the accumulation of amyloid-β (Aβ) in the brain. In particular, the 42-amino acid form, Aβ1-42, is thought to play a key role in the disease. It is therefore of interest that diverse compounds, known as γ-secretase modulators (GSM), can selectively decrease Aβ1-42 production without inhibiting the production of other forms of Aβ. Here we describe the novel discovery of synergistic inhibition of Aβ by certain combinations of GSMs. Cell cultures were treated with pairwise combinations of GSMs to determine how Aβ peptide production was affected. Analysis of isobolograms and calculation of the combination index showed that BMS-869780 and GSM-2 were highly synergistic. Additional combinations of GSMs revealed that inhibition of Aβ occurred only when one GSM was of the "acid GSM" structural class and the other was of the "non-acid GSM" class. A total of 15 representative acid/non-acid GSM combinations were shown to inhibit Aβ production, whereas 10 pairwise combinations containing two acid GSMs or containing two non-acid GSMs did not inhibit Aβ. We also discovered that lasalocid, a natural product, is a potent GSM. Lasalocid is unique in that it did not synergize with other GSMs. Synergism did not translate in vivo perhaps because of biochemical differences between the cell culture model and brain. These findings reinforce the pharmacological differences between different structural classes of GSMs, and may help to exploit the potential of γ-secretase as a drug target.


Culturally Appropriate Assessment of Functional Impairment in Diverse Children: Validation of the ADHD-FX Scale With an At-Risk Community Sample.
In an effort to reduce disparities in ADHD diagnoses and treatment across cultures, the current study sought to establish initial psychometric and cultural properties of the ADHD-FX: a culturally sensitive assessment measure of functional impairment related to ADHD for diverse families. Fifty-four Latino parents (44 mothers and 10 fathers) of school-aged children completed the ADHD-FX, as well as several other measures assessing child behavior and parent acculturation. The ADHD-FX demonstrated adequate reliability (as demonstrated by internal consistency and test-retest reliability), psychometric construct validity (as demonstrated by associations with theoretically related measures), and cultural validity (as demonstrated by or lack of associations with acculturation measures). Initial psychometric and cultural properties suggest that the ADHD-FX is a reliable, valid, and culturally appropriate measure to assess functional impairment related to ADHD (i.e., difficulties with academic achievement, social competence, and familial relationships) in an at-risk, school-aged population.


Lattice gauge theories in the presence of a linear gauge-symmetry breaking.
We study the effects of gauge-symmetry breaking (GSB) perturbations in three-dimensional lattice gauge theories with scalar fields. We study this issue at transitions in which gauge correlations are not critical and the gauge symmetry only selects the gauge-invariant scalar degrees of freedom that become critical. A paradigmatic model in which this behavior is realized is the lattice CP^{1} model or, more generally, the lattice Abelian-Higgs model with two-component complex scalar fields and compact gauge fields. We consider this model in the presence of a linear GSB perturbation. The gauge symmetry turns out to be quite robust with respect to the GSB perturbation: the continuum limit is gauge invariant also in the presence of a finite small GSB term. We also determine the phase diagram of the model. It has one disordered phase and two phases that are tensor and vector ordered, respectively. They are separated by continuous transition lines, which belong to the O(3), O(4), and O(2) vector universality classes, and which meet at a multicritical point. We remark that the behavior at the CP^{1} gauge-symmetric critical point substantially differs from that at transitions in which gauge correlations become critical, for instance at transitions in the noncompact lattice Abelian-Higgs model that are controlled by the charged fixed point: in this case, the behavior is extremely sensitive to GSB perturbations.


Carbon monoxide-mediated humoral pathway for the transmission of light signal to the hypothalamus.
The gaseous messenger carbon monoxide (CO) is released from the eye into ophthalmic venous blood depending on the intensity of sunlight. Numerous neurohormones and other regulatory factors permeate from venous blood into arterial blood in the perihypophyseal vascular complex (PVC) and are transferred to the brain by the humoral pathway. This study was designed to determine whether elevated CO in ophthalmic venous blood (OphVB) affects the expression of clock genes and their transcriptional factors in the hypothalamus. Mature males of a wild boar and pig crossbreed (n=24) were used for the study. Autologous plasma with increased concentrations of CO was infused into the ophthalmic sinus (OphS) of the experimental group (n=12). The expression of clock genes (Per1, Per2, Cry1, Cry2, Rev-erb α and Rev-erb β) and the genes of their regulators (Bmal1, Npas2, Clock, Ror β) was estimated in two hypothalamic structures involved in the reception and transmission of light signal (the preoptic area (PA) and dorsal hypothalamus (DH)). We demonstrated that the expression of clock genes and the genes of their regulatory factors in the experimental group was altered compared with control, both in the PA and DH. The response to an increased concentration of CO differed between individual genes and the hypothalamic regions. The expression of Per1 which, according to many authors, is regulated by light, was increased in animals treated with CO both in the PA and DH, and regardless of the time of day and season. In conclusion, the current results seem to confirm the hypothesis on the function of CO in humoral transfer from the eye to structures related to the reception and transmission of light signal and the effect of CO on clock gene expression.


Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary tuberculosis among HIV-infected adults in Ghana-findings from the DETECT HIV-TB study.
Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy. HIV-infected adults eligible for antiretroviral therapy were prospectively enrolled from Korle-Bu Teaching Hospital in Ghana and followed for minimum 6 months. We applied the LAM test on urine collected as a spot and early morning sample. Diagnostic accuracy was analysed for a microbiological TB reference standard based on sputum culture and Gene Xpert MTB/RIF results and for a composite reference standard including clinical follow-up data. Performance of sputum smear microscopy was included for comparison. Of 469 patients investigated for TB, the LAM test correctly identified 24/55 (44 %) of microbiologically confirmed TB cases. Sensitivity of the LAM test was positively associated with hospitalisation (67 %), Modified Early Warning Score > 4 (57 %) and subsequent death (71 %). LAM test specificity was 95 % increasing to 98 % for the composite reference standard. A two-sample LAM test strategy did not improve test performance. Using concentrated sputum for Ziehl-Neelsen and fluorescence microscopy in combination yielded a sensitivity of 31/55 (56 %) that increased to 35/55 (64 %) when the LAM test was added. Surprisingly, nontuberculous mycobacteria were cultured in 34/469 (7 %) and associated with a positive LAM test (p = 0.008). LAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two-sample strategy. A rigorous sputum microscopy strategy had superior sensitivity, but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients.


[Laboratory investigation of endocrine function - interpretation of results and pitfalls].
Endocrine disorders are common in internal medicine. Diagnosis of endocrine diseases are usually based on patient history, clinical assessment and laboratory investigations. Thereby, biochemical analyses are used to confirm clinical diagnosis, to assess the need for treatment and to monitor disease progression, in particular to ascertain treatment efficacy. This article will focus on frequently used laboratory investigations for endocrine diseases such as diabetes, thyroid dysfunction, male hypogonadism and adrenal insufficiency. In particular, pre-analytical and analytical variability of biochemical measures as well as its significance in clinical practice will be discussed.