Accounting for alignment uncertainty in phylogenomics.
Uncertainty in multiple sequence alignments has a large impact on phylogenetic analyses. Little has been done to evaluate the quality of individual positions in protein sequence alignments, which directly impact the accuracy of phylogenetic trees. Here we describe ZORRO, a probabilistic masking program that accounts for alignment uncertainty by assigning confidence scores to each alignment position. Using the BALIBASE database and in simulation studies, we demonstrate that masking by ZORRO significantly reduces the alignment uncertainty and improves the tree accuracy.


Crocetin Alleviates Inflammation in MPTP-Induced Parkinson's Disease Models through Improving Mitochondrial Functions.
Parkinson's disease (PD) is the second most common neurodegenerative disease. Crocetin, derived from saffron, exerts multiple pharmacological properties, such as anti-inflammatory, antioxidant, antifatigue, and anticancer effects. However, the effect of crocetin on PD remains unclear. In this study, we designed experiments to investigate the effect of crocetin against MPTP-induced PD models and the underlying mechanisms. Our results showed that crocetin treatment attenuates MPTP-induced motor deficits and protects dopaminergic neurons. Both in vivo and in vitro experiments demonstrated that crocetin treatment decreased the expression of inflammatory associated genes and inflammatory cytokines. Furthermore, crocetin treatment protected mitochondrial functions against MPP+ induced damage by regulating the mPTP (mitochondrial permeability transition pore) viability in the interaction of ANT (adenine nucleotide translocase) and Cyp D (Cyclophilin D) dependent manner. Therefore, our results demonstrate that crocetin has therapeutic potential in Parkinson's disease.


Electrophysiological characterization of uncoupled mutants of LacY.
In this study of the lactose permease of Escherichia coli (LacY), five functionally irreplaceable residues involved specifically in H(+) translocation (Arg302 and Glu325) or in the coupling between protonation and sugar binding (Tyr236, Glu269, and His322) were mutated individually or together with mutant Glu325 → Ala. The wild type and each mutant were purified and reconstituted into proteoliposomes, which were then examined using solid-supported-membrane-based electrophysiology. Mutants Glu325 → Ala or Arg302 → Ala, in which H(+) symport is abolished, exhibit a weakly electrogenic rapid reaction triggered by sugar binding. The reaction is essentially absent in mutant Tyr236 → Phe, Glu269 → Ala, and His322 → Ala, and each of these mutations blocks the electrogenic reaction observed in the Glu325 → Ala mutant. The findings are consistent with the interpretation that the electrogenic reaction induced by sugar binding is due to rearrangement of charged residues in LacY and that this reaction is blocked by mutation of each member of the Tyr236/Glu269/His322 triad. In addition, further support is provided for the conclusion that deprotonation is rate limiting for downhill lactose/H(+) symport.


[The retardation of DNA synthesis in adjacent replicon clusters in the lymphocytes of patients with Down's syndrome as a model of premature aging].
In peripheral blood lymphocytes taken from 7 patients with Down syndrome (DS) and 2 normal donors, using DNA fiber autoradiography, we estimated the rate of DNA-chain growth, which depends oil the number of simultaneously replicating adjacent replicon clusters, but not on the rate of fork movement. No difference was found in the rate of fork movement in these cells. 6 of 7 DS patients showed a significant reduction in the rate of DNA-chain growth as compared to that in normal control. Thus, a new molecular defect in DS lymphocytes has ben first revealed. Besides, new arguments have been provided in favour of genetic heterogeneity of this genetic disorder belonging to premature ageing diseases. Relation of molecular DNA replication defects with ageing is discussed.


Molecular remission and non-Hodgkin's lymphoma.
Non-Hodgkin's lymphomas are highly sensitive to treatment and complete clinical responses are often achieved. However, disease recurrence is common and is caused by the persistence of malignant lymphoma cells at a level below the limits of detection by conventional assessment such as clinical examination, bone marrow morphology and CT scans. This minimal residual disease can be detected using molecular techniques such as the polymerase chain reaction (PCR), and treatments capable of eliminating minimal residual disease are described as producing molecular remission. Molecular assessment is now commonly used as a measure of outcome in clinical trials of novel therapies for the treatment of lymphoma. The evidence for using molecular remission as a surrogate marker of clinical response in this setting is reviewed and the significance of minimal residual disease in determining prognosis and planning treatment strategies is addressed.


Superhydrophobic Silica Aerogels and Their Layer-by-Layer Structure for Thermal Management in Harsh Cold and Hot Environments.
Personal thermal management (PTM) materials have recently received considerable attention to improve human body thermal comfort with potentially reduced energy consumption. Strategies include passive radiative cooling and warming. However, challenges remain for passive thermal regulation of one material or structure in both harsh hot and cold environments. In this work, silica aerogels derived from sodium silicate were prepared through a solvent-boiling strategy, where hydrophobization, solvent exchange, sodium purification, and ambient pressure drying (HSSA) proceeded successively and spontaneously in a one-pot process. This strategy leads to the synthesis of superhydrophobic silica aerogels with extremely low energy consumption without out the use of an ion-exchange resin or low surface tension solvents. Silica aerogels possess a high specific surface area (635 m2/g), high contact angle (153°), and low thermal conductivity (0.049 W/m K). A layer-by-layer (LBL) structure including the silica aerogel layer and an extra phase change material layer was designed. The structure demonstrates dual-functional thermal regulation performance in both harsh cold (-30 °C) and hot (70 °C) environments, where the time to reach equilibrium is postponed, and the inner temperature of the LBL structure can be kept above 20 °C in harsh cold environments (-30 °C) and below 31 °C in harsh hot environments (70 °C). A proof-of-concept experimental setup to simulate the illumination of sunlight also proved that the inside temperature of a model car protected by the LBL structure was below 28 °C, while the outside temperature was 70 °C. In addition, these results are well supported by theoretical COMSOL simulation results. The findings of this work not only provide an eco-friendly approach to synthesize silica aerogels but also demonstrate that the LBL structure is a robust dual-functional PTM system for thermal regulation in both harsh hot and cold environments.


Patients with questionable penicillin (beta-lactam) allergy: Causes and solutions.
In Europe, North America, and Australia, 5% to 10% of the population are now classified as penicillin (β-lactam) allergic. Only ~ 10% of these questionable diagnoses, mostly made in childhood, can be confirmed by allergy diagnostics. The aim of this review is to show causes and consequences as well as recommendations for dealing with the often questionable diagnosis of penicillin (β-lactam) allergy (BLA). An incorrect BLA diagnosis may negatively impact antibiotic treatment needed in the future, by using a less effective antibiotic or using a broad-spectrum antibiotic, for example, further exacerbating the problem of increasing antibiotic resistance. Accordingly, there is growing pressure from antibiotic stewardship programs to critically challenge the BLA diagnosis. Conservatively, a suspected BLA is reviewed by an allergist using medical history, skin testing, laboratory testing, and provocation. This clarification is costly and is not remunerated in the German health care system; that is the reason why this testing is only offered in a few specialized clinics and practically not at all in general practice. In view of thousands of affected patients, additional strategies are needed to treat patients with a low risk of hypersensitivity reaction despite suspected allergy with a β-lactam antibiotic. In recent years, various methods have been proposed to eliminate suspected allergy as promptly as possible and directly before necessary treatment with a β-lactam antibiotic, including standardized history (also in the form of an algorithm), skin test with immediate reading after 15 minutes, or administration of a small test dose. Investigations of small case series and also multi-center studies to date have yielded promising results in terms of feasibility and safety. Of the large number of patients with (questionable) BLA, most have never been tested and - if antibiotic treatment becomes necessary - simply receive an alternative antibiotic. The diagnosis of BLA therefore requires new approaches besides classical allergy testing to critically question BLA.


Electron ionization of the nucleobases adenine and hypoxanthine near the threshold: a combined experimental and theoretical study.
Electron ionization of the DNA nucleobase, adenine, and the tRNA nucleobase, hypoxanthine, was investigated near the threshold region (∼5-20 eV) using a high-resolution hemispherical electron monochromator and a quadrupole mass spectrometer. Ion efficiency curves of the threshold regions and the corresponding appearance energies (AEs) are presented for the parent cations and the five most abundant fragment cations of each molecule. The experimental ionization energies (IEs) of adenine and hypoxanthine were determined to be 8.70 ± 0.3 eV and 8.88 ± 0.5 eV, respectively. Quantum chemical calculations (B3LYP/6-311+G(2d,p)) yielded a vertical IE of 8.08 eV and an adiabatic IE of 8.07 eV for adenine and a vertical IE of 8.51 eV and an adiabatic IE of 8.36 eV for hypoxanthine, and the lowest energy optimized structures of the fragment cations and their respective neutral species were calculated. The enthalpies of the possible reactions from the adenine and hypoxanthine cations were also obtained computationally, which assisted in determining the most likely electron ionization pathways leading to the major fragment cations. Our results suggest that the imidazole ring is more stable than the pyrimidine ring in several of the fragmentation reactions from both adenine and hypoxanthine. This electron ionization study contributes to the understanding of the biological effects of electrons on nucleobases and to the database of the electronic properties of biomolecules, which is necessary for modeling the damage of DNA in living cells that is induced by ionizing radiation.


Respiratory functions in Kalaripayattu practitioners.
Kalaripayattu, an ancient traditional martial art form of Kerala, is considered as the basis for all martial arts viz. Karate, Kungfu, etc. physiological studies are more concentrated on Karate, Kungfu and other martial arts due to their global acceptance. Considering the limited knowledge available regarding the physiological profiles of Kalaripayattu practitioners, the present study was taken up for filling the lacunae in the field. Lung function tests were carried out in ten Kalari practitioners. Residual volume was measured by indirect method. Higher lung volumes and flow rates were achieved in Kalari practitioners compared to age and height-matched controls. Better mechanical factors and lower airway resistance influenced during Kalari practice might have benefited in improving hung volumes and flow rates.


Ultrastructure of the uterus in an ovariectomized gecko (Hemidactylus turcicus) after administration of exogenous estradiol.
The uterus of an oviparous gecko, Hemidactylus turcicus, was analysed after ovariectomized females underwent a period of treatment (up to 14 days) with exogenous estradiol. Analysis focused on the uterine mucosa, which is made up of an epithelial layer and an underlying lamina propria containing the shell glands. These tissues are thought to be responsible for secretion of the eggshell components and were thus chosen for analysis using transmission electron microscopy. In ovariectomized females, the epithelial layer was low and cuboidal with minimal/no differentiation or secretory activity. Treatment with exogenous estradiol resulted in a significant increase in cell height associated with gradual differentiation of the epithelium. Development of non-ciliated cells included production of secretory granules (low electron density) at the apical cell surface. The shell glands showed less obvious changes over the course of treatment. Shell glands contained two cell types: dark cells with darkly staining nuclei and organelles, and light cells with very indistinct nuclei and organelles, except for prominent rough endoplasmic reticulum and free ribosomes. This study provides results consistent with published light microscopy studies for other reptiles and additionally provides ultrastructural details of reptilian uterine development not previously available.


Positive effects of temperature and growth conditions on enzymatic and antioxidant status in lettuce plants.
The contents of two bioactive compounds (polyphenols and flavonoids) and their antioxidant and enzyme activities were determined in the leaves of six lettuce (Latuca sativa L.) cultivars subjected to 4 different day/night temperatures for 6 weeks. The total polyphenol and anthocyanin contents and the corresponding antioxidant activities were the highest at 13/10°C and 20/13°C, followed by 25/20°C and 30/25°C. The enzymatic activities of polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL) were also the highest at low day/night temperatures, but the peroxidase (POD) activity was decreased at low day/night temperatures and increased at high day/night temperatures. The most significant positive correlation existed between anthocyanin content and PPO activity, total polyphenols and their antioxidant activities. The results showed that at relatively low temperatures, lettuce plants have a high antioxidant and enzymatic status. These results provide additional information for the lettuce growers.


Renal function and renal function reserve in insulin-dependent diabetic patients during (near) normoglycaemia.
Twenty-three normoalbuminuric (N) and 7 microalbuminuric (M) insulin-dependent diabetes mellitus (IDDM) patients were studied under (near) normoglycaemic conditions. They were reasonably well controlled during the period preceding the renal function test (HbA1: N = 7.6 +/- 1.3%, N = 8.0 +/- 2.2%; normal less than 6.0%). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using the clearances of 125I-thalamate and 131I-hippuran, respectively. The renal reserve filtration capacity (RRFC) was tested by using a combination of a liquid mixed meal and an amino acid infusion. Blood glucose levels were kept as constant as possible throughout the testing procedure, both under baseline (BL) conditions and after stimulation (S). Under such (near) normoglycaemic conditions, no BL GFR values exceeding 150 ml/min/1.73 m2 could be established. Furthermore, a RRFC could be established in all patients. Both groups showed a comparatively larger increase in GFR (N 13.0 +/- 3.8%, M 10.8 +/- 3.6%) than in ERPF (N 4.8 +/- 7.0%, M 2.2 +/- 5.8%; % delta GFR vs. % delta ERPF p less than 0.01), resulting in a higher filtration fraction (FF) during stimulation (N: BL FF 0.25 +/- 0.03 vs. S FF 0.27 +/- 0.03, p less than 0.01; M: BL FF 0.25 +/- 0.01 vs. S FF 0.27 +/- 0.01, p less than 0.05). This suggests afferent vasodilation during stimulation in these (near) normoglycaemic, reasonably well-controlled IDDM patients, a situation comparable to that in non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives.
The 13 amino acid toxic peptide from the marine snail Conus geographus, conotoxin GI, blocks the acetylcholine receptor at the neuromuscular junction. In this report, we describe a method for analyzing disulfide bonding in nanomole amounts of small cystine-rich peptides. The procedure involves partial reduction and a double-label alkylation of cysteine residues. Using this method, we show that the natural conotoxin GI has a (2-7, 3-13) disulfide configuration. The structure of conotoxin GI has been confirmed by chemical synthesis. The preparation and purification of molecularly homogeneous, iodinated derivatives of this toxin are also described. All derivatives, including the [diiodohistidine,diiodotyrosine]conotoxin GI, retained at least half of the biological activity of unmodified toxin. Since the tetraiodinated toxin, which is greater than 25% by weight iodine, retains considerable toxicity, unmodified histidine and tyrosine residues in conotoxin GI are not crucial for biological activity.


Integrated electrochemical lateral flow immunoassays (eLFIAs): recent advances.
The discovery of electroactive nano-biomaterials and the development of flexible electrodes have increased the interest in applications of integrated electrochemical lateral flow immunoassays (eLFIAs), which integrate electrochemical nanotags and flexible electrodes on test strips that can easily detect small biomolecules. Compared with colorimetric, optical, magnetic and other highly sensitive detection methods, the electrochemical detection technique is well developed with high sensitivity, selectivity and repeatability. Moreover, the increasing compatibility of interfaces with miniature potentiometers has allowed electrochemical sensors to become more integrated, automated and intelligent, highlighting their huge potential in future developments. This review discusses the relevant eLFIA research over the past 20 years. The basic principles, electrode assemblies, electrochemical labeling strategies and electrical signal detection methods are summarized and analyzed in detail. Finally, perspectives on the current challenges facing eLFIA and its future outlook are presented.


Antibacterial, anti-biofilm, and anti-adhesive activities of melittin, a honeybee venom-derived peptide, against quinolone-resistant uropathogenic Escherichia coli (UPEC).
Here, we demonstrated the in vitro and in vivo antibacterial and anti-biofilm activities of melittin, a peptide derived from honeybee venom, against uropathogenic Escherichia coli (UPEC) resistant to quinolones. The minimum inhibitory concentration (MIC) of melittin varied from 0.5 to 8 μM. The bactericidal effect was considered rapid and potent (ranging from 3.0 to 6.0 h after incubation) against a quinolone-resistant and Extended Spectrum Beta-lactamase (ESBL)-producing UPEC strain. Prior exposure to melittin did not reduce the MIC of the quinolones tested, but it decreased the MIC of ceftizoxime by 8-fold due to its ability to form pores in the membrane. Furthermore, melittin disrupted mature biofilms (39.58% at 32 μM) and inhibited the adhesion of this uropathogen to the surfaces of urethral catheter. These results show that melittin is a promising molecule that can be incorporated into invasive urethral medical devices to prevent urinary infections caused by multidrug-resistant UPECs.


Do Gender and Age Moderate the Relationship between Friendship Quality and Non-Suicidal Self-Injury in Community Children and Adolescents?
In the present study, we investigated the relationship between friendship quality (dimensions) and non-suicidal self-injury (NSSI) as well as the moderating role of gender and age in this relationship. The sample consisted of 463 children and adolescents (50.10% female, age range: 9-17 years). Friendship quality and NSSI were measured using the Friendship Qualities Scale (FQS; Bukowski, Hoza, & Boivin, 1994) and the Self Harm Inventory (SHI; Sansone, Wiederman, & Sansone, 1998), respectively. Overall, total friendship quality and NSSI were significantly and negatively related. Additionally, the relationship between total friendship quality and NSSI was moderated by gender and age. Specifically, girls with low friendship quality reported more NSSI; whereas for boys an opposite effect was found. As for age, friendship quality and NSSI were positively related in older participants. In younger participants, a relationship between friendship quality and NSSI seemed rather absent. This study highlights the important association between friendship quality and NSSI, as well as gender- and age-related differences in this association, which should be taken into account in the prevention and treatment of NSSI.


Molecular identification of reovirus in broiler type flocks in Golestan province, Iran.
Avian reovirus (ARV) has a global distribution in nature and most clinical signs are found in broiler type chickens. This study was conducted to detect and identify reovirus infections from vaccinated breeder chickens and their progenies. A total of 20 tissue and blood samples were collected from vaccinated broiler breeders and their progenies with gastrointestinal or performance problems during peak production. Antibody titers were measured by indirect enzyme-linked immunosorbent assay (ELISA) tests. RNA extraction from tissue samples was performed and cDNA was prepared and directly used in the polymerase chain reaction (PCR). Nucleotide sequences were bilaterally determined using internal primers. The analysis of the nucleotide sequences and their related amino acids was performed by the specialized Molecular Evolutionary Genetics Analysis software (6th version). The virus variant was detected in two vaccinated broiler breeders and five broiler flocks. The vaccine strains in breeder flocks included S1133, SS412, 1733, 2408 belonging to genotype 1 from the reovirus phylogenetic tree. Sequence 7 from the isolated reovirus based on the σC revealed that they were different from the reovirus vaccine, and that 6 isolates belonged to genotype 1 of the phylogenetic tree while 1 isolate belonged to branch 4 of the phylogenetic tree. The study showed that the new reovirus strain isolated from vaccinated birds differs from common strains used in the vaccines. It is therefore essential to prevent the effects of the field reovirus on the performance of industrial poultry, by updating and inventing new commercial vaccines, live and killed, against the reovirus.


Interval timing under variations in the relative validity of temporal cues.
Two groups of pigeons were trained to respond on a white center key to a fixed-interval, 60-s schedule of reinforcement signaled by the onset of a side-key cue (S+ training). In additional training sessions, S+ trials alternated between S- trials in which a different side-key cue signaled nonreinforcement after 60 s (S+/S- training). For one group, S+/S- training sessions followed S+ training, and for the other group, S+/S- training preceded S+ training. Peak-time curves obtained from extended nonrewarded probe trials inserted among training trials showed loss of control by time during S+/S- training relative to S+ training. A follow-up experiment showed that this result was not caused by a difference in probability of reinforcement. We suggest that attention to time was weakened by the introduction of visual cues that were more valid predictors of trial outcomes.


Effects of nitrogen on mesophyll cell division and epidermal cell elongation in tall fescue leaf blades.
Leaf elongation rate (LER) in grasses is dependent on epidermal cell supply (number) and on rate and duration of epidermal cell elongation. Nitrogen (N) fertilization increases LER. Longitudinal sections from two genotypes of tall fescue (Festuca arundinacea Schreb.), which differ by 50% in LER, were used to quantify the effects of N on the components of epidermal cell elongation and on mesophyll cell division. Rate and duration of epidermal cell elongation were determined by using a relationship between cell length and displacement velocity derived from the continuity equation. Rate of epidermal cell elongation was exponential. Relative rates of epidermal cell elongation increased by 9% with high N, even though high N increased LER by 89%. Duration of cell elongation was approximately 20 h longer in the high- than in the low-LER genotype regardless of N treatment. The percentage of mesophyll cells in division was greater in the high- than in the low-LER genotype. This increased with high N in both genotypes, indicating that LER increased with cell supply. Division of mesophyll cells adjacent to abaxial epidermal cells continued after epidermal cell division stopped, until epidermal cells had elongated to a mean length of 40 micrometers in the high-LER and a mean length of 50 micrometers in the low-LER genotype. The cell cycle length for mesophyll cells was calculated to be 12 to 13 hours. Nitrogen increased mesophyll cell number more than epidermal cell number: in both genotypes, the final number of mesophyll cells adjacent to each abaxial epidermal cell was 10 with low N and 14 with high N. A spatial model is used to describe three cell development processes relevant to leaf growth. It illustrates the overlap of mesophyll cell division and epidermal cell elongation, and the transition from epidermal cell elongation to secondary cell wall deposition.


Glomerular cytoarchitectures in chemosensory systems of arachnids.
In most animals the central pathways of olfactory systems are associated with glomerular neuropil and lack topographic mapping of sensory inputs. Among arthropods, the insect and crustacean olfactory (antennal) pathways are typical examples. Two orders of chelicerate arthropods, the scorpions and solpugids (Cl. Arachnida), present striking exceptions to this generalization. The major chemosensory organs of scorpions are the pectines, two ventral appendages that contact the substrate intermittently as the animal searches for food or mates. In solpugids chemosensory input is from the antennalized pedipalps and first leg pairs, and from ten fan-shaped malleoli extending ventrally to the substrate from the 4th leg pair. The pectinal and malleolar sensory systems have highly ordered arrangement of 10(5) to 10(6) primary chemoreceptors, with one (pectines) forming a two-dimensional array and the other (malleoli) assembled in a linear array. The spatial frequencies of these chemoreceptive inputs exceed 100/mm and 1000/mm, respectively, indicating a capacity for resolving structure of chemical deposits on substrates. Using several histological and axonal tracing techniques, the organization of pectinal and malleolar central projections has been resolved. The pectinal projection terminates posteriorly in the cephalothoracic mass and shows a high degree of topographic precision, perhaps to the level of individual receptors in the sensory field. This chemosensory 'map' is imposed on laminar cytoarchitecture posteriorly in the brain but merges anteriorly into glomerular substructures. The sensory projection from the malleoli shows less topographic order with fewer and larger glomeruli reminiscent of the insect olfactory system. These comparisons between arthropod taxa suggest that olfactory projections are, to varying degrees, typically glomerular but may evolve topographic and laminar organization when the stimulus field is of fixed form.


[Forensic medical assessment of the role of the injury and pathology in the development of basal subarachnoidal hemorrhage].
The comparative analysis of clinical and pathomorphological forensic medical literature and the original investigations of basal subarachnoidal hemorrhage carried out by the author during 25 years provided a basis for morphological diagnostics of traumatic and non-traumatic subarachnoidal hemorrhage with special reference to variants of forensic medical assessment of the role of injuries and pathologies in the development of basal subarachnoidal hemorrhage.


[Judicial and contentious aspects of anesthesia].
The practice of anaesthesia is surrounded by the same legal texts as in other medical fields and by a decree, which is specific to it. This decree notably prescribes a preliminary consultation by an anaesthetist, in a lapse of time allowing change to eventually the planned strategy or to optimise preoperative care. It is therefore important that all medical data useful to the patient assessment should be available at this time. Since the application of professional standards, claims related to the anaesthetic practice have decreased in the United States, especially because of the reduction in perioperative hypoxic injuries. It should be noted that the development of such standards aims first at improving patient's care. Claims reduction could be consider as a secondary consequence. Other means of improving our practice deserve to be developed, such as national confidential surveys.


CCN1 sensitizes esophageal cancer cells to TRAIL-mediated apoptosis.
TRAIL is one of the best anti-cancer molecules in our body. It kills a variety of cancer cells that are resistant to conventional chemotherapy, without causing much negative impact on normal cells, because its death receptors are almost exclusively found on cancer cells. However, some cancer cells are not sensitive to TRAIL treatment, even though they express its death receptors. A second molecule is needed to help TRAIL to complete its mission. Finding such molecules now becomes a top priority in cancer research. Our study shows that CCN1 is such a molecule. CCN1 was highly expressed in the esophageal epithelium of the patients suffering from gastroesophageal reflux disease, but faded away as the situation worsened towards adenocarcinoma. Treating the tumor cells with CCN1 resulted in apoptosis, while the same treatment to the normal cells only nourished cell growth. It was TRAIL that mediated this process. Apparently, CCN1 altered the expression profile of TRAIL and its receptors in tumor cells, namely, activating TRAIL and its death receptors and shutting down its decoy receptors. CCN1 and TRAIL worked as a team to put the cancer cells to death, as elimination of either one failed apoptosis.


Attitudes of medical students towards men who have sex with men living with HIV: implications for social accountability.
To explore the attitudes that medical students in Haiti harbour toward Men who have Sex with Men living with HIV in order to better understand how stigma and other factors may impair healthcare, and to explore suggestions of opportunities in line with the values of social accountability. This study employed a qualitative design by using a grounded theory approach regarding the context of Haiti. We used purposive sampling to select the 22 research participants. In-depth interviews were conducted, audio-recorded, transcribed and analyzed using an inductive content analysis approach. Although stigmatizing attitudes emerged through the findings, medical students expressed willingness to provide Men who have Sex with Men with adequate health services in relation to HIV care. Their expressions were based on the Men who have Sex with Men's comprehensive right to receive equitable care, the moral responsibility of healthcare professionals, their perception of health disparities and the HIV global risk reduction. Participants pointed out that the medical education curriculum did not consider sexual health and specificities of sexual minorities and suggested a more inclusive and socially accountable training based on equity and quality. The students expressed favourable attitudes regarding health services to Men who have Sex with Men even though some layered stigmatizing attitudes emerged through the discussions. They all lacked skills on how to handle health specificities of sexual minorities. These findings recommend a revision of the medical education curriculum in regard to social accountability principles.


Altered expression of inflammatory cytokine receptors in response to LPS challenge through interaction between intestinal epithelial cells and lymphocytes of Peyer's patch.
The intense innate immunological activities occurring at the enteric mucosal surface involve interactions between intestinal epithelial cells and immune cells. Our previous studies have indicated that Peyer's patch lymphocytes may modulate intestinal epithelial barrier and ion transport function in homeostasis and host defense via cell-cell contact as well as cytokine signaling. The present study was undertaken using the established co-culture system of Caco-2 epithelial cells with lymphocytes of Peyer's patch to investigate the expression of IL-8 and IL-6 cytokines and cytokine receptors in the co-culture system after challenge with Shigella F2a-12 lipopolysaccharide (LPS). The human colonic epithelial cell line Caco-2 was co-cultured with freshly isolated lymphocytes from the murine Peyer's patch either in the mixed or separated (isolated but permeable compartments) co-culture configuration, and was challenged with Shigella F2a-12 LPS for 8 h. The level of mRNA expressions of human interleukin-8 (hIL-8), human interleukin-8 receptor (hIL-8R), mouse interleukin-8 receptor (mIL-8R), mouse interleukin-6 (mIL-6), mouse interleukin-6 receptor (mIL-6R) and human interleukin-6 receptor (hIL-6R) was examined by semi-quantitative PCR. In both co-culture groups, hIL-8 expression of Caco-2 cells was decreased, and hIL-8R expression was increased compared to the Caco-2 alone group. Upon LPS challenge, hIL-8 expression from the Caco-2 cells of both co-culture groups was higher than in the Caco-2 control group. The increased hIL-8 expression of Caco-2 cells in the separated co-culture group is correlated with a decreased hIL-8R expression and an increased mIL-8R expression. In the mixed co-culture group, the increased expression of hIL-8 was associated with the upregulated hIL-8R expression on Caco-2 cells and downregulated mIL-8R on murine Peyer's patch lymphocytes (PPL). mIL-6 expression from mouse PPL was also upregulated by LPS in mixed co-culture. However, upon the treatment with LPS, hIL-6R expression of Caco-2 cells was decreased in the mixed co-culture, but increased in separated co-culture. The data suggest that release of hIL-8 from epithelial cells may act on lymphocytes through a paracrine pathway, but it may also act on the epithelial cells themselves via an autocrine pathway. The data also suggest that the release of mIL-6 from Peyer's patch lymphocytes affects epithelial cells in a paracrine fashion.


Homogeneity Permitted Robust Connection for Additive Manufacturing Stretchable Electronics.
Interface is the Achilles' heel in flexible electronics, where slipping, delamination, or cracking resulting from the intrinsic mechanical property mismatch of different materials might fail the device or cause degradation. Robust connections with strong interfacial strength and low interfacial impedance are highly desired in all kinds of flexible devices, especially when they require stretchability. Here, a new strategy of employing homogeneity is proposed to facilely achieve robust connection without introducing a third-party interlayer. The key to this strategy is implementing different functions in the same component materials, and in this work, this strategy is demonstrated by exploring the uniformity of carbon nanotube (CNT) in thermoplastic polyurethane (TPU) elastomer. Tuning the uniformity of CNT in TPU elastomer, two kinds of CNT-TPU composites (CTCs) are fabricated. They present contrasting properties of conductivity (281 folds), Young's modulus (7.1 folds), and strain sensitivity (15.7 folds) with the same weight fraction of CNT (15 wt %), and thus they can respectively act as strain sensor and interconnector in all-CNT-based stretchable strain monitoring electronics. The interlocking effect caused by spontaneous entanglement of surface polymer chains and the reconstruction of percolation network at the interface during drying confer the connection with robustness. The practical value of this strategy has been exemplified by the fabrication of a robust epidermis device via additive manufacturing. This epidermis device is patterned in a fractal motif for conformal contact and can sensitively monitor body motions and radial artery pulse.


[Combined effects of high temperature and carbon monoxide on heat stress protein levels in rat brain and viscera].
Combined effects of high temperature and carbon monoxide (CO) on the amounts of heat stress protein 60 (HSP 60) and 70 (HSP 70) in rat brain and viscera were studied by western dot blot technique. Results showed that (1) amounts of HSP 60 in rat brain, spleen and kidney, as well as its rectal temperature, increased with CO concentrations, while those in heart decreased; and both of them showed synergistic effects on those in spleen and kidney, antagonistic ones in brain and liver, and synergistic ones of lowering them in heart; (2) amounts of HSP 70 changed with CO concentrations in five rat viscera, with synergism in brain, and antagonism in other organs; and (3) amounts of HSP 60 and 70 in most rat viscera and their body temperature were the most sensitive to 693.6 mg/m3 of CO.


Placebo treatments, informed consent and 'the grip of a false picture'.
It is widely supposed that the prescription of placebo treatments to patients for therapeutic purposes is ethically problematic on the grounds that the patient cannot give informed consent to the treatment, and is therefore deceived by the physician. This claim, I argue, rests on two confusions: one concerning the meaning of 'informed consent' and its relation to the information available to the patient, and another concerning the relation of body and mind. Taken together, these errors lead naturally to the conclusion that the prescription of placebos to unwitting patients is unethical. Once they are dispelled, I argue, we can see that providing 'full' information against a background of metaphysical confusion may make a patient less informed and that the 'therapeutic' goal of relieving the patient of such confusions is properly the duty of the philosopher rather than the physician. Therapeutic placebos therefore do not violate the patient's informed consent or the ethical duties of the doctor.


Data Resource Profile of Shizuoka Kokuho Database (SKDB) Using Integrated Health- and Care-insurance Claims and Health Checkups: The Shizuoka Study.
Analyzing real-world data, including health insurance claims, may help provide insights into preventing and treating various diseases. We developed a database covering Shizuoka Prefecture (Shizuoka Kokuho Database [SKDB]) in Japan, which included individual-level linked data on health- and care-insurance claims and health checkup results. Anonymized claims data on health insurance (National Health Insurance [age <75 years] and Latter-Stage Elderly Medical Care System [age ≥75 years]), care insurance, subscriber lists, annual health checkups, and all dates of death were collected from 35 municipalities in Shizuoka Prefecture. To efficiently link claims and health checkups, unique individual IDs were assigned using a novel procedure. From April 2012 to September 2018, the SKDB included 2,230,848 individuals (men, 1,019,687; 45.7%). The median age (min-max) of men and women was 60 (0-106) and 62 (0-111) years, respectively. During the study period, the median subscription time was 4.4 years; 40.8% of individuals continuously subscribed for the 6.5 years; 213,566 individuals died. Health checkup data were available for 654,035 individuals, amounting to 2,469,648 records. Care-service recipient data were available for 283,537 individuals; they used care insurance to pay for care costs. SKDB, a population-based longitudinal cohort, provides a comprehensive dataset covering health checkups, disorders, medication, and care service. This database may provide a robust platform to identify epidemiological problems and generate hypotheses for preventing and treating disorders in the elderly.


Solid phase synthesis of carbocyclic l-2'-deoxynucleosides.
[reaction: see text] Carbocyclic L-2'deoxynucleosides 17 were synthesized on solid phase in four steps from the appropriately protected intermedate 11. The Mitsunobu reaction was used as a condensation method between the carbocyclic moiety and heterocyclic bases. The regioselectivity of the carbocyclic nucleosides was compared between the solid and solution phase syntheses.


Electrophysiologic cardiac effects of the new local anesthetic IQB-9302 and of bupivacaine in the anesthetised dog.
Local anesthetics are not free from potentially fatal complications. Therefore every new local anesthetic should be tested to demonstrate a lower, or at least similar, degree of toxicity over clinically used analogs. Most toxic effects from local anesthetics affect the cardiac electrophysiologic function, so the aim of this study was to characterize the electrophysiologic effects of a new long-acting local anesthetic (IQB-9302, Ciprocaine), and compare them with those of bupivacaine in the anesthetized dog. Eight Beagle dogs received three increasing infusion doses of either IQB-9302 or bupivacaine. Under isoflurane anesthesia, dogs were instrumented to monitor cardiovascular (cardiac output, arterial and venous blood pressures) and cardiac electrophysiologic data (sinus and atrioventricular (AV) node function, atrial, nodal and ventricular conduction times, and refractoriness). Only the highest dose of both drugs induced hemodynamic or electrophysiologic alterations: cardiac output and heart rate were reduced while blood pressures remained unchanged. Atrial and intranodal conduction times and atrial refractoriness increased similarly with both anesthetics, but to a slightly lesser extent with IQB-9302. Significant increases in His-Purkinje and intraventricular conduction times were the most severe noxious effects and occurred only with large doses of either drug. IQB-9302 was slightly less toxic than bupivacaine and, unlike this latter drug, potentially fatal arrhythmias were not induced. IQB-9302 has hemodynamic and cardiac electrophysiologic effects similar to those caused by bupivacaine. Nevertheless, slightly less toxic effects were derived from IQB-9302 administration than with bupivacaine, and, unlike the latter, the former might be less proarrhytmogenic. The new long-acting local anesthetic IQB-9302 may offer clinical advantages compared with bupivacaine.


Worrisome histologic alterations following fine needle aspiration of the thyroid.
To investigate worrisome histologic alterations following fine needle aspiration (FNA) of the thyroid (WHAFFT). Of 1,890 FNA thyroid cases, 265 underwent surgical excision. The histologic sections of these cases were studied for WHAFFT lesions. Thirty control cases were also studied. WHAFFT lesions were present in 38.49% of cases. Acute lesions were seen in 30 and chronic in 72 cases. Control cases did not show WHAFFT lesions. The common lesions were hemorrhage and fibrosis. Worrisome lesions, like nuclear atypia, vascular changes, capsular pseudoinvasion and metaplasia, were present in 32 (12.07%) cases. Considering the large number of FNAs and reduction in the number of thyroid excisions, the advantages of FNA are manifold as compared to the few diagnostic problems. Misdiagnosis can be avoided with awareness of WHAFFT lesions.


Compact lanthanum hexaboride hollow cathode.
A compact lanthanum hexaboride hollow cathode has been developed for space applications where size and mass are important and research and industrial applications where access for implementation might be limited. The cathode design features a refractory metal cathode tube that is easily manufactured, mechanically captured orifice and end plates to eliminate expensive e-beam welding, graphite sleeves to provide a diffusion boundary to protect the LaB6 insert from chemical reactions with the refractory metal tube, and several heater designs to provide long life. The compact LaB(6) hollow cathode assembly including emitter, support tube, heater, and keeper electrode is less than 2 cm in diameter and has been fabricated in lengths of 6-15 cm for different applications. The cathode has been operated continuously at discharge currents of 5-60 A in xenon. Slightly larger diameter versions of this design have operated at up to 100 A of discharge current.


Multifunctional upconversion-magnetic hybrid nanostructured materials: synthesis and bioapplications.
The combination of nanotechnology and biology has developed into an emerging research area: nano-biotechnology. Upconversion nanoparticles (UCNPs) have attracted a great deal of attention in bioapplications due to their high chemical stability, low toxicity, and high signal-to-noise ratio. Magnetic nanoparticles (MNPs) are also well-established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI). As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging. Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional upconversion-magnetic hybrid nanostructured materials. The hybrid nanostructures, which combine UCNPs with MNPs, exhibit upconversion fluorescence alongside superparamagnetism property. Such structures could provide a platform for enhanced bioimaging and controlled drug delivery. We expect that the combination of unique structural characteristics and integrated functions of multifunctional upconversion-magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nano-bioapplications.


Depicting Binding-Mediated Translocation of HIV-1 Tat Peptides in Living Cells with Nanoscale Pens of Tat-Conjugated Quantum Dots.
Cell-penetrating peptides (CPPs) can translocate across cell membranes, and thus have great potential for the cellular delivery of macromolecular cargoes. However, the mechanism of this cellular uptake process is not yet fully understood. In this study, a time-lapse single-particle light-sheet microscopy technique was implemented to obtain a parallel visualization of the translocating process of individual human immunodeficiency virus 1 (HIV-1) transactivator of transcription (Tat) peptide conjugated quantum dots (TatP-QDs) in complex cellular terrains. Here, TatP-QDs served as nanoscale dynamic pens, which depict remarkable trajectory aggregates of TatP-QDs on the cell surface. Spectral-embedding analysis of the trajectory aggregates revealed a manifold formed by isotropic diffusion and a fraction of directed movement, possibly caused by interaction between the Tat peptides and heparan sulfate groups on the plasma membrane. Further analysis indicated that the membrane deformation induced by Tat-peptide attachment increased with the disruption of the actin framework in cytochalasin D (cyto D)-treated cells, yielding higher interactions on the TatP-QDs. In native cells, the Tat peptides can remodel the actin framework to reduce their interaction with the local membrane environment. Characteristic hot spots for interaction were detected on the membrane, suggesting that a funnel passage may have formed for the Tat-coated particles. This finding offers valuable insight into the cellular delivery of nanoscale cargo, suggesting an avenue for direct therapeutic delivery.


Spin-label Studies of Membranes in Rye Protoplasts during Extracellular Freezing.
Protoplasts isolated from epicotyls of nonhardened winter rye seedlings were spin-labeled with the N-oxyl-4-4-dimethyloxazolidine derivatives of 5-ketostearic (5NS) and 16-ketostearic (16NS) acids. Spectra of the membrane-bound labels showed motional broadening with a rotational correlation time of 1.5 x 10(-8) second for 5NS and 1.5 x 10(-10) second for 16NS at 0 C. A procedure was developed to follow membrane changes in these protoplasts during extracellular freezing. With freezing, molecular motion of 5NS, but not of 16NS, spin probes was restricted. The increase in molecular order near the hydrated end of the membrane did not result from lowered temperatures inasmuch as no such change was observed in supercooled samples. These changes are probably due to dehydration of protoplast membranes during extracellular freezing. Similar results were obtained with multilayered egg yolk lecithin and are consistent with previous observations of changes in lecithin multibilayers during dehydration. Such alterations in membrane order might lead to irreversible membrane damage during extracellular freezing of plant cells.


Accuracy of different devices to measure temperature.
Although erroneous temperature measurement can lead to unneeded patient treatment, nursing staff typically use devices interchangeably without knowledge of any difference in results. A study comparing different methods of temperature measurement in postoperative patients is described.


Gas-chromatographic assay of free phenytoin in ultrafiltrates of plasma: test of a new filtration apparatus and specimen stability.
I describe a gas-chromatographic procedure involving a nitrogen detector for "free" (or "unbound") phenytoin in the concentration range 0.2-4.0 mg/L in ultrafiltrates of plasma. The CV (n = 10) for the assay was 2.9% for a 0.49 mg/L concentration, 1.5% for 2.02 mg/L. The sensitivity was 0.05 mg/L. The ultrafiltration process ("Ultra-Free" filters) used to separate the free phenytoin fraction from the bound fraction was tested. The mean of and CV for free phenytoin concentrations measured in eight replicate serum filtrates were 0.68 mg/L and 15%; for eight replicate plasma filtrates the values were 0.42 mg/L and 2.9%. Thus serum is not suitable for this procedure. Storage of plasma before filtration under a wide variety of times and temperatures has an insignificant effect upon the filtration process. Some evidence was found of occasional protein "leakage" through the filters.


The evolving role of itraconazole, fluconazole and terbinafine in the treatment of tinea capitis.
Tinea capitis has become an increasing public health concern in the last decade. The increased incidence of the disease; its sometimes subtle, nonspecific clinical presentation; and the development of tolerance to griseofulvin therapy have led to the need for alternative safe, efficacious, inexpensive therapies that work rapidly. Itraconazole, fluconazole and terbinafine all possess pharmacologic and pharmacokinetic characteristics that theoretically would make them ideal therapies for tinea capitis. However, few randomized double blind controlled studies using these agents have been published. Thus far none have been conducted in the United States. The best available data support the utility and safety of the new antifungals in the treatment of tinea capitis. However, one must keep in mind that they are not yet approved by the Food and Drug Administration for this indication. Safety and cost considerations favor terbinafine for the treatment of T. tonsurans infections. M. canis infections may respond better to itraconazole, but good controlled studies to confirm this speculation have not been conducted. Short course and pulse dosing are particularly exciting options that may decrease cost and lower the risk of adverse side effects. Further useful information will hopefully come from future randomized double blind studies that will include patients from the United States. Studies using standardized definitions of disease, cure and appropriate follow-up evaluation of clinical and mycologic cure will best identify the optimal therapy for pediatric tinea capitis infections. The new systemic antifungals may provide more therapeutic options for fungal infections of the scalp. Note added in proof A recent trial comparing short course terbinafine and intraconazole therapy demonstrated that 2-week therapy with either drug provided good results and high cure rates (Jahangir M, et al. Br J Dermatol 1998;139:672-4).


Use of a locking compression plate as an external fixator for repair of a tarsometatarsal fracture in a bald eagle (Haliaeetus leucocephalus).
We describe the successful treatment of a tarsometatarsal fracture in a mature bald eagle (Haliaeetus leucocephalus) using a locking compression plate as an external fixator. The anatomy of the area (inelastic dermis and minimal subcutaneous space) and the high forces placed on a fracture at that site necessitated a unique approach to fixation. The unconventional use of a locking compression plate as an external fixator was minimally invasive, well tolerated by the eagle, and provided adequate stability in opposing fracture forces. This technique may serve as a method of fixation for tarsometatarsal fractures in other large avian species.


The effects of cold whirlpool on power, speed, agility, and range of motion.
The purpose was to determine if cold whirlpool treatment decreases functional performance equally regardless of gender. A secondary aim was to determine if there is a gradual increase in functional performance across time. Twenty-one college-aged subjects volunteered to participate in this study and were required to perform four measures of functional performance including: counter movement vertical jump, T-test, 36.58-meter dash (40-yard), and active range of motion of the ankle. Participants were treated with a 20 minute, 10 degree Celsius cold whirlpool following the pre-test of a given functional performance measure. Participants demonstrated significant decreases in counter movement vertical jump, T-test, and 40-yard dash performance immediately following treatment. Vertical jump performance remained impaired for at least 32 minutes. While both the T-test and 40-yard dash were affected for 7 and 22 minutes post- treatment, respectively. Participants also demonstrated significant decreases in peak power and average power immediately after and for 32 minutes post-treatment. Dorsiflexion was significantly decreased 7 and 12 minutes following treatment. There were no differences for plantar flexion, inversion, or eversion. These data suggest functional performance was affected immediately following and for up to 32 minutes after cold whirlpool treatment. It was also evident that there is a gradual performance increase for each measure of functional performance across time. Therefore, the consequences should be carefully considered before returning athletes to activity following cold whirlpool treatment. Key pointsCryotherapy is a common and highly effective modality in treating acute and chronic athletic injuries.The results indicated that cold whirlpool does have an immediate and subsequent effect on functional performance.Understanding how cold whirlpool adversely affects functional performance allows clinicians to continue using this modality before vigorous athletic activity.


Implementation of a standard outcome set in perinatal care: a qualitative analysis of barriers and facilitators from all stakeholder perspectives.
To improve their quality, healthcare systems are increasingly focused on value delivered to patients. For perinatal care, the International Consortium for Health Outcomes Measurement (ICHOM) proposed a patient-centred outcome set with both clinical and patient-reported measures for pregnancy and childbirth (PCB set). This study aimed to identify factors that affect the implementation of the PCB set at the pre-implementation stage, using the consolidated framework for implementation research (CFIR). In this qualitative study, we conducted semi-structured interviews amongst a purposive sample of key stakeholders within an obstetric care network (OCN): 1) patients, 2) perinatal care professionals involved in the full cycle of perinatal care, and 3) policy makers, including hospital managers, administrative staff and health care insurers. While the CFIR guided data capture and structuring, thematic analysis revealed overarching themes that best reflected the barriers and facilitators from different stakeholder perspectives. Within these overarching themes, the CFIR constructs were maintained. Interviews were conducted with 6 patients, 16 professionals and 5 policy makers. Thematic analysis supported by the CFIR framework identified four main themes: the instrument and its implementation process, use in individual patient care, use in quality improvement, and the context of the OCN. Important barriers included professional workload, data reliability, and interprofessional and interorganizational collaboration. Potential facilitators were the PCB set's direct value in individual care, interprofessional feedback and education, and aligning with existing systems. Prominent variations between stakeholder groups included the expected patient burden, the level of use, transparency of outcomes and the degree of integrated care. This study clarified critical factors that affect successful implementation of the PCB set in perinatal care. Practice recommendations, suggested at multiple levels, can enable structural patient-centred care improvement and may unite stakeholders towards integrated birth care.


Comparative cytogenetic and DNA flow cytometric analysis of 150 bone and soft-tissue tumors.
Samples from 48 benign and 102 malignant bone and soft-tissue tumors were analyzed cytogenetically and by DNA flow cytometry. Clonal chromosome abnormalities were found in 82 tumors and normal karyotypes in 68; 61 tumors were DNA-non-diploid and 89 were diploid. The cytogenetically abnormal tumors were used for comparison between the 2 types of investigation; 45 of these tumors were DNA-diploid and 37 were DNA-non-diploid. There was, with few exceptions, good correspondence between the quantitative estimates of genomic changes by the 2 methods, indicating that the cells cytogenetically analyzed from short-term cultures are representative of the in vivo cell populations. Discrepancies were primarily found in cases with indexes above 1.5, in which the DNA index was higher than the chromosome index. The chromosome analysis suggested that skewed stemline (G0/G1) peaks in the diploid region in DNA histograms indicate the presence of cell populations with small net quantitative genomic changes, although not all such populations were detected by DNA flow cytometric analysis. The view that one of the peaks in bimodal stemline DNA histograms with narrow peaks represents a non-diploid cell population was also corroborated. On average, the cell populations giving rise to double stemlines in DNA histograms showed quantitatively larger genomic changes than those that gave rise to broad or skewed diploid G0/G1 peaks. The findings indicate that these histogram profiles are not artifactual but reflect chromosomal changes in the tumor parenchyma.


Polyposis coli, craniofacial exostosis and astrocytoma: the concomitant occurrence of the Gardner's and Turcot syndromes.
Up to 60% of the patients with known adenomatous polyposis coli may present hyperostosis of the skull and facial bones, and/or a susceptibility to fibromas. This is known as the Gardner's syndrome, and is considered as an allelic variant of familial adenomatous polyposis (FAP). Also, although very rare, an adenomatous polyposis coli may occur with malignant tumors of the central nervous system, known as Turcot syndrome. If both syndromes are different phenotypic presentation of FAP, this would explain a simultaneous occurrence. We report the history of a patient who showed clinical signs of the simultaneous occurrence of both Gardner's and Turcot syndromes. The syndromes are compared, and in view of the literature, a genetic explanation for the concomitant occurrence is discussed. Evidence obtained from the literature to consider Turcot syndrome as a phenotype of FAB is as follows: (1) The occurrence of Gardner's and Turcot syndromes in one family, but in different members; (2) The presence of congenital hypertrophic retinal pigmented epithelium (CHRPE), which correlates with the expression of polyps in FAP patients, in both syndromes; (3) Linkage of the Turcot phenotype to the adenomatous polyposis coli locus by genetic markers. Evidence obtained from this case report indicates that there is a manifestation of both syndromes in one patient together with a positive family history for FAP. This concomitant occurrence of both Gardner's and Turcot syndromes in one patient clinically supports genetic and ophthalmic investigation to consider Turcot syndrome (like Gardner's syndrome) as a phenotypic variant of FAP. Patients with FAP should be examined for the presence of Gardner's syndrome. In case a Gardner's syndrome is suspected, a computed tomography scan of the brain is recommended because of the possible existence of a simultaneous Turcot syndrome.


Adverse effect of pretransplant blood transfusions on survival of matched kidney allografts in dogs.
Previous studies from our laboratory have already shown that pretransplant blood transfusions from third-party donors significantly prolong kidney allograft survival in mismatched unrelated immunosuppressed dogs. In the present study, a similar effect was found in related donor-recipient pairs mismatched for two haplotypes (P less than 0.05); no significant effect was observed in one-haplotype-mismatched combinations (P = 0.34). Pretransplant blood transfusions did not have a beneficial influence on kidney allograft survival in immunosuppressed DLA-identical, related donor recipient pairs. After withdrawal of immunosuppressive therapy, transfused dogs in this group rejected their kidneys even more frequently than did nontransfused dogs (P = 0.16). A comparable undesired effect of blood transfusions was found for recipients of unrelated kidneys which were identical with respect to DLA-A, B, and D: transfused recipients of those kidneys rejected the graft significantly more often than the untransfused controls (P less than 0.01). The most likely explanation for this adverse effect is that blood transfusions given to the recipient may cause crossimmunization for undefined, probably minor, antigens of the donor kidney. Apparently, differences arising from these minor histocompatibility antigens become manifest only after withdrawal of the immunosuppressive therapy. Furthermore, it appeared that the effect of histocompatibility matching on kidney allograft survival is less for transfused than for untransfused dogs. The most important conclusion is, however, that the beneficial effect of blood transfusions appears to be dependent on the degree of matching: while blood transfusions are on the whole beneficial for unmatched kidneys, they are likely to have no effect, or even to be harmful, for matched kidneys.


What policies and policy processes are needed to ensure that people with psychiatric disabilities have access to appropriate housing?
This paper uses data from a South Australian case study of a period of mental health reform (2000-2005) to answer the question of how different policy networks set agenda and implement policy to ensure that people with psychiatric disabilities have access to appropriate housing. Qualitative methods were used, including interviews (n = 31) and focus groups (n = 8) with non-government organisations (NGOs), consumers and carers and professionals from health, disability and housing sectors, and participant observation with South Australian NGOs (n = 52). These data were supported by a thematic analysis of national and State (i.e. South Australian) policies in mental health and housing sectors. The research indicated that, despite a number of 'inter-sectoral projects' and regional networks, the health and housing sectors were essentially separate policy systems with little integration. It also concluded that the absence of strategic integration across sectors leads to inadequate housing for people with a psychiatric disability. Research participants considered the need for better collaboration secondary to the need for additional housing and support resources and political commitment to such resources. A number of barriers and enablers to policy agenda setting and collaboration were identified. The paper concludes with a discussion of policy and policy processes which will support housing outcomes for people with psychiatric disability.


Selective aspects of the epizootiology of Parathelohania iranica (Microsporidia: Amblyosporidae).
Parathelohania is a genus of microsporidia that preferentially attacks Anopheline mosquitoes. This study explored some selective aspects of the epizootiology of Parathelohania iranica (Microsporidia: Amblyosporidae) in its malaria mosquito host Anopheles superpictus s.l. (Diptera: Culicidae). For this study, Sar-rok Village, a place adjacent to the type locality of the parasite, located at the central western part of Iran was visited twice a month to collect host larvae from mid-summer to mid-autumn of 2017-2021. Patent infections were detected by the whitish discoloration of the involved segments. Superficially uninfected larvae were reared up to 26 days in the insectary to elucidate hidden infections. Molecular investigation and laboratory trials were conducted to evaluate the possibility of secondary infections in subsequent days. Morphological characters were used to determine the sex of larvae and adults. Data were entered in SPSS 23.0 and analyzed with relevant statistical tests as needed. In total, 584 P. iranica infected larvae of An. superpictus s.l. were collected in the study years at day zero (D0). Extended observations in the insectary revealed that 849 larvae (84.2 %), 22 dead pupae (2.2 %), and 137 emerged adults (13.6 %) were also infected. In the first two years of the study, the mean infection rate for D0 and D0 + D1-D26 infections was 6.25 % and 15.6 %, respectively. Exposure experiments indicated that subsequent infections in larvae (D1-D26) were not affected by a possible source in the accompanying field water. Patent (D0) infections were seasonal and had about a month delay compared to the general population of larvae. Concealed infections of larvae (D1-D26) were significantly more frequent in late mosquito season (P < 0.01). It is proposed that the gradual decrease of ambient temperature and the shortening of day length postpones the growth and development of P. iranica in the affected larvae. Both sexes of larvae were involved and none of them survived beyond a couple of days. The frequency of infections in adult males (5.8 %) were significantly more than females (4 %) (P = 0.02). The infections of larvae were more common in the late mosquito season, and the infections of adults were more frequent in the early mosquito season. This suggests the relative importance of vertical and horizontal routes of transmission in early and late mosquito seasons, respectively. However, age-specific data revealed that only 26 % of hidden infections of larvae (D1-D26) were stemmed from I to II age group. This implies that the vertical route may be less efficient than the horizontal route in the transmission of P. iranica to the mosquito host. These inferences should be verified with further field and laboratory investigations.


The improbability of prebiotic nucleic acid synthesis.
Many accounts of the origin of life assume that the spontaneous synthesis of a self-replicating nucleic acid could take place readily. Serious chemical obstacles exist, however, which make such an event extremely improbable. Prebiotic syntheses of adenine from HCN, of D,L-ribose from adenosine, and of adenosine from adenine and D-ribose have in fact been demonstrated. However these procedures use pure starting materials, afford poor yields, and are run under conditions which are not compatible with one another. Any nucleic acid components which were formed on the primitive earth would tend to hydrolyze by a number of pathways. Their polymerization would be inhibited by the presence of vast numbers of related substances which would react preferentially with them. It appears likely that nucleic acids were not formed by prebiotic routes, but are later products of evolution.


The effectiveness of Ergon Instrument-Assisted Soft Tissue Mobilization, foam rolling, and athletic elastic taping in improving volleyball players' shoulder range of motion and throwing performance: a pilot study on elite athletes.
[Purpose] The purpose of this pilot study was to investigate the effectiveness of instrument-assisted soft tissue mobilization (IASTM), foam rolling, and athletic elastic taping on improving elite volleyball players' shoulder range of motion (ROM) and throwing performance. [Participants and Methods] Fifteen elite male volleyball players (mean age: 24 ± 4.54 years; mean height: 177 ± 0.08 cm; mean weight: 81 ± 7.71 kg) received shoulder Ergon IASTM, foam rolling, and elastic taping treatment in random order on both upper extremities once a week for three weeks. Pre-and post-treatment assessments of their shoulders' ROM and functional throwing performance were performed. [Results] Ergon IASTM technique resulted in significantly higher shoulder flexion ROM values than foam rolling and elastic taping. Foam rolling, in turn, showed better results than athletic elastic taping. Moreover, the Ergon IASTM technique resulted in significantly higher OSP values than athletic elastic taping. No significant differences were observed between the therapeutic interventions in terms of FTPI. [Conclusion] This pilot study on elite athletes provides evidence that both IASTM and foam rolling techniques may improve their passive shoulder ROM compared to elastic athletic taping while Ergon IASTM can also enhance their shoulder throwing performance.


A case of cerebral endometriosis causing catamenial epilepsy.
We present the second reported patient with cerebral endometriosis. She had repetitive partial seizures on the first day of her menstrual cycle. The seizures were controlled by danazol after the causative lesions were surgically removed.


Intradialytic hypotension.
Intradialytic hypotension (IDH) is common in children during conventional, 4 hour haemodialysis (HD) sessions. The declining blood pressure (BP) was originally believed to be caused by ultrafiltration (UF) and priming of the HD circuit, however emerging data now supports a multifactorial aetiology. Therefore strategies to improve haemodynamic stability need to be diverse and address specific patient requirements or risks. In the treatment of IDH immediate action is required to stop or reduce the severity of symptoms that may precede or follow. Typically UF is slowed or stopped, a fluid bolus is given and in resistant cases the HD session is prematurely discontinued. Patients complete their treatment under-dialysed and volume expanded. Chronically, repeated episodes of IDH cause devastating, multi-system morbidity with an increased risk of mortality. This had provided the impetus for more haemodynamically friendly dialysis prescriptions that attenuate the risk of IDH. During pediatric HD several preventative strategies have been tested but with variable success. Of these, dialysate sodium profiling, UF guided by relative blood volume (RBV) algorithms, cooling and intradialytic mannitol appear to be the most effective. However in refractory cases one may be left with no option but to switch dialysis modality to haemodiafiltration (HDF) or more frequent or prolonged HD regimens.


Relationship between adverse childhood experiences and homelessness and the impact of axis I and II disorders.
We investigated the links between homelessness associated with serious mental and physical healthy disparities and adverse childhood experiences (ACEs) in nationally representative data, with Axis I and II disorders as potential mediators. We examined data from the National Epidemiologic Survey of Alcohol and Related Conditions in 2001-2002 and 2004-2005, and included 34,653 participants representative of the noninstitutionalized US population who were 20 years old or older. We studied the variables related to 4 classes of Axis I disorders, all 10 Axis II personality disorders, a wide range of ACEs, and a lifetime history of homelessness. Analyses revealed high prevalences of each ACE in individuals experiencing lifetime homelessness (17%-60%). A mediation model with Axis I and II disorders determined that childhood adversities were significantly related to homelessness through direct effects (adjusted odd ratios = 2.04, 4.24) and indirect effects, indicating partial mediation. Population attributable fractions were also reported. Although Axis I and II disorders partially mediated the relationship between ACEs and homelessness, a strong direct association remained. This novel finding has implications for interventions and policy. Additional research is needed to understand relevant causal pathways.


Tips for leaders, part III: leadership during a time of change.
Good leaders anticipate the need for change and manage change well. However, the members of an organization generally oppose major change. There are many risks for the people and the group during a period of significant change. It is important that the leader communicates the reasons for the changes, involves as many people as possible in the process, develops a clear plan for implementation, and communicates well with the followers.


US budget impact analysis of esketamine nasal spray in major depressive disorder with acute suicidal ideation/behavior.
Background: Esketamine nasal spray plus an oral antidepressant is approved in adults with major depressive disorder with acute suicidal ideation or behavior (MDSI). Methods: A budget impact analysis from a US payer perspective was performed with a hypothetical 1-million-member plan, using pharmacy and medical costs associated with adding esketamine plus an oral antidepressant to usual care. Results: Estimated annual total healthcare costs of managing patients with MDSI increased from $32,988,247 without esketamine to $34,161,188 in Year 3 with esketamine (primarily due to medical costs). The per-member-per-month incremental costs were $0.02, $0.06 and $0.10 in Years 1, 2 and 3, respectively. Conclusion: Incorporation of esketamine results in a modest estimated impact on the annual budget over a 3-year time horizon.


Microwave absorption spectroscopy of DNA.
By utilizing a novel approach to microwave spectrometry, we have measured the absolute absorption spectrum of plasmid DNA (pUC8.c2), in buffered aqueous solution, from 5 to 20 GHz. Our technique does not suffer from the same experimental difficulties that plague other methods. We observe no absorption resonances in this frequency range, but we do see broadband differences, between DNA and pure buffer, that are attributable to changes in the ionic conductivity of the solutions. These results constitute the first verification, by a totally different technique, of the absence of resonances in the microwave absorption spectrum of DNA, and the first data obtained by any technique in the 10-20-GHz band.


A Novel Method: Super-selective Adrenal Venous Sampling.
Primary aldosteronism (PA) and subclinical Cushing's syndrome (SCS) are conditions in which the adrenal glands autonomously produce excessive amounts of aldosterone and cortisol, respectively. The conventional adrenal venous sampling (cAVS) method collects blood samples from both adrenal central veins and is useful for identifying the laterality of excess hormone production in a unilateral lesion(s), as documented in PA cases. In cAVS, plasma cortisol concentrations (PCCs) are used to normalize plasma aldosterone concentrations (PACs). A novel "super-selective" adrenal venous sampling (ssAVS) method was developed using a micro-catheter, which collects blood samples from adrenal tributary veins (TVs). PACs in ssAVS samples do not require PCC normalization because samples contain a limited amount of systemic venous blood, if any. The ssAVS method enabled segmental lesion(s) to be detected in both adrenal glands, which may be treated by bilateral adrenalectomy, thereby sparing lesion-free segment(s). Right and left adrenals typically have three TVs each, i.e., the superior, lateral, and inferior TVs in the right adrenal as well as the superior-median, superior-lateral, and lateral TVs in the left adrenal. In the ssAVS method, specific parent catheters and a technique to handle them are required, and have been described herein. Furthermore, ssAVS results from three cases of PA are presented: bilateral aldosterone-producing adenoma (APA) (Case #1), left APA and right possible cortisol-producing adenoma causing SCS (Case #2), and idiopathic hyperaldosteronism in which bilateral adrenal segments produced excessive amounts of aldosterone (Case #3). The ssAVS method is not difficult for expert angiographers, and, thus, is recommended worldwide to treat PA cases for which cAVS does not represent a viable surgical treatment option.


Endothelium-independent vasorelaxation by the selective alpha estrogen receptor agonist propyl pyrazole triol in rat aortic smooth muscle.
This study investigated the signalling mechanism of the relaxant responses to the estrogen receptor (ERalpha) agonist PPT (propyl pyrazole triol) in endothelium-denuded rat aortic rings. Several compounds, including protein kinase G (PKG) inhibitors and potassium channel inhibitors, were tested against PPT-dependent rat aortic relaxation. Cyclic GMP and cytosolic calcium responses to PPT in isolated aortic smooth muscle were investigated in parallel. PPT vasorelaxation was largely reduced by the selective ERalpha antagonist methyl-piperidinopyrazole (MPP; -91.6+/-2.5%), by the selective PKG inhibitor Rp-8-Br-cGMP (-78.6+/-4.9%), by the specific soluble guanylyl cyclase inhibitor ODQ (1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one; -85.3+/-5.2%) and to a lesser extent by the selective BKCa (large-conductance calcium- and voltage-activated potassium channel) inhibitor iberiotoxin (-59.3%), the selective IKCa (intermediate-conductance calcium-activated potassium channel) inhibitor TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole; -50.7%) and the voltage-gated potassium channel inhibitor 4-aminopyridine (-40.8%). In isolated aortic smooth muscle, PPT strongly enhanced the cyclic GMP content (+144%) and Rp-8-Br-cGMP largely reduced the PPT-dependent calcium signal (-80.8%). ERalpha receptor stimulation in rat aortic smooth muscle evokes a PKG-signalling pathway, likely triggering relaxation by BKCa and IKCa channel opening.


[Preliminary study on monoclonal antibodies against Cysticercus cellulosae].
In order to produce valuable monoclonal antibodies for immunodiagnosis of cysticercosis, hybridoma technique was adopted using the fusion of splenic lymphocytes from BALB/c mice immunized with Cysticercus cellulosae antigens and the myeloma cell line NS-1. Through screening and cloning, three monoclonal antibody cell lines have been established. Immunoglobulin subclasses of 3 lines were determined to be IgG1. These monoclonal antibodies were found to be highly specific and without cross reaction with Echinococcus granulosus hydatid cyst and Cysticercus fasciolasis. Antigen fractions specifically reacting to monoclonal antibodies were demonstrated with Western blot method. The results showed that specific reaction bands of SCW located in 25 kDa and 17 kDa regions.


[The importance of risk factors in emergence and development of ishemic heart deasease].
The prognostic value of some risk factors in emergence of ishemic heart disease and insult were analyzed. 1500 healthy men from 40 to 59 years old were under investigation. Reinvestigation of 71% responses was conducted after 10 years. The prognostic role of different risk factors of ishemic heart disease was revealed. Multifactorial prophylaxis carried out for 5 years among men aged 40 to 59 years brought about a significant decrease in the total death rate (by 22,2%), Mainly because of the lowering of the death rate due to cardiovascular diseases (by 41,3%), determined by a reduction of these indicators among persons who initially had coronary heart disease. The data indicate that in order to reach a positive effect, the primary care should be exercised for a longer time. At the same time, the prophylactic measures are to be multifactorial and include not only correction of risk factors but also the screening and treatment of patients suffering from coronary heart disease.


Perceptions of Risk and Vulnerability Following Exposure to a Major Natural Disaster: The Calgary Flood of 2013.
Many studies have examined the general public's flood risk perceptions in the aftermath of local and regional flooding. However, relatively few studies have focused on large-scale events that affect tens of thousands of people within an urban center. Similarly, in spite of previous research on flood risks, unresolved questions persist regarding the variables that might influence perceptions of risk and vulnerability, along with management preferences. In light of the opportunities presented by these knowledge gaps, the research reported here examined public perceptions of flood risk and vulnerability, and management preferences, within the city of Calgary in the aftermath of extensive flooding in 2013. Our findings, which come from an online survey of residents, reveal that direct experience with flooding is not a differentiating factor for risk perceptions when comparing evacuees with nonevacuees who might all experience future risks. However, we do find that judgments about vulnerability-as a function of how people perceive physical distance-do differ according to one's evacuation experience. Our results also indicate that concern about climate change is an important predictor of flood risk perceptions, as is trust in government risk managers. In terms of mitigation preferences, our results reveal differences in support for large infrastructure projects based on whether respondents feel they might actually benefit from them.


Developing a palliative care service for children in the Queen Elizabeth Central Hospital, Blantyre, Malawi.
There are too few palliative care services for children in resource poor countries. Health carers are overwhelmed with cases of acute illness that need their urgent attention, and chronically ill children with life-limiting diseases have been sidelined. The HIV epidemic in southern Africa revealed the huge needs in our own hospital, and in 2002, we started a hospital-based paediatric palliative care service. It was the first in Africa. We describe here how it developed and expanded in the ensuing years and how it has affected our staff, the children and their families in our care.


Mapping Thyroarytenoid and Cricothyroid Activations to Postural and Acoustic Features in a Fiber-Gel Model of the Vocal Folds.
Any specific vowel sound that humans produce can be represented in terms of four perceptual features in addition to the vowel category. They are pitch, loudness, brightness, and roughness. Corresponding acoustic features chosen here are fundamental frequency (fo ), sound pressure level (SPL), normalized spectral centroid (NSC), and approximate entropy (ApEn). In this study, thyroarytenoid (TA) and cricothyroid (CT) activations were varied computationally to study their relationship with these four specific acoustic features. Additionally, postural and material property variables such as vocal fold length (L) and fiber stress (σ) in the three vocal fold tissue layers were also calculated. A fiber-gel finite element model developed at National Center for Voice and Speech was used for this purpose. Muscle activation plots were generated to obtain the dependency of postural and acoustic features on TA and CT muscle activations. These relationships were compared against data obtained from previous in vivo human larynx studies and from canine laryngeal studies. General trends are that fo and SPL increase with CT activation, while NSC decreases when CT activation is raised above 20%. With TA activation, acoustic features have no uniform trends, except SPL increases uniformly with TA if there is a co-variation with CT activation. Trends for postural variables and material properties are also discussed in terms of activation levels.


Association between intraoperative starch use and postoperative kidney dysfunction in patients undergoing major gastro-intestinal surgery: A propensity score-matched analysis.
The impact of intraoperative starch-based fluid therapy on postoperative kidney dysfunction in patients undergoing major abdominal surgery is uncertain. Low molecular weight starch is expected to cause less postoperative kidney dysfunction. This retrospective study evaluated the impact of intraoperative 6% hydroxyethyl starch on postoperative renal dysfunction. The primary outcome of this study was postoperative acute kidney injury as per KDIGO definition within 72 hours of surgery. This study analysed data from 461 patients with a median (interquartile range) age of 45 (33-58) years, and 48.2% of all patients were female. The proportion (95% confidence interval) of patients who developed acute kidney injury was 0.18 (0.14-0.21); 62.9% of patients had acute kidney injury stage I, 32% had acute kidney injury stage II, and the rest were acute kidney injury stage III. In the propensity score-matched sample, the average treatment effect of intraoperative colloid use on postoperative serum creatinine at day 3 (p = 0.32), duration of postoperative intensive care unit stay (p = 0.97), duration of hospital stay (p = 0.37), postoperative worst international normalised ratio (p = 0.92), and postoperative transfusion requirement (p = 0.40) were not statistically significant. Intraoperative use of low molecular weight hydroxyethyl starch use was not associated with postoperative kidney dysfunction and coagulopathy in adult patients undergoing major open abdominal surgery.


Effects of moderate hypoxia on action potential and contraction of rabbit ventricular muscle.
Experiments were performed on rabbit right ventricular strips in order to investigate the effects of moderate hypoxia on electrical and mechanical activities of this preparation. The results indicate that a slow inward current (Isi) is responsible for overshoot (OS) and the plateau phase of the action potential (AP). Hypoxia (pO2 = 65-70 mmHg; 8.66-10.0 kPa) induced a rapid shortening of AP and an increase in the phase-3 slope. It also markedly reduced twitch tension and time to peak tension, and increased resting tension. The resting potential (RP), OS and maximum rate of depolarization of phase O were not affected during 60 min of hypoxic perfusion. Isoproterenol under this condition had a positive inotropic effect and also increased AP duration (APD) measured at -60 mV, having a less pronounced effect on the plateau phase. MnCl2 in hypoxic conditions drastically reduced OS indicating that even in this condition, Isi was present. These results suggest that an increase in gK is responsible for the hypoxia-induced reduction in APD. This also partially explains the maintenance of RP during hypoxic incubation.


Development of a Single-Cycle Infectious SARS-CoV-2 Virus Replicon Particle System for Use in Biosafety Level 2 Laboratories.
Research activities with infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently permitted only under biosafety level 3 (BSL3) containment. Here, we report the development of a single-cycle infectious SARS-CoV-2 virus replicon particle (VRP) system with a luciferase and green fluorescent protein (GFP) dual reporter that can be safely handled in BSL2 laboratories to study SARS-CoV-2 biology. The spike (S) gene of SARS-CoV-2 encodes the envelope glycoprotein, which is essential for mediating infection of new host cells. Through deletion and replacement of this essential S gene with a luciferase and GFP dual reporter, we have generated a conditional SARS-CoV-2 mutant (ΔS-VRP) that produces infectious particles only in cells expressing a viral envelope glycoprotein of choice. Interestingly, we observed more efficient production of infectious particles in cells expressing vesicular stomatitis virus (VSV) glycoprotein G [ΔS-VRP(G)] than in cells expressing other viral glycoproteins, including S. We confirmed that infection from ΔS-VRP(G) is limited to a single round and can be neutralized by anti-VSV serum. In our studies with ΔS-VRP(G), we observed robust expression of both luciferase and GFP reporters in various human and murine cell types, demonstrating that a broad variety of cells can support intracellular replication of SARS-CoV-2. In addition, treatment of ΔS-VRP(G)-infected cells with either of the anti-CoV drugs remdesivir (nucleoside analog) and GC376 (CoV 3CL protease inhibitor) resulted in a robust decrease in both luciferase and GFP expression in a drug dose- and cell-type-dependent manner. Taken together, our findings show that we have developed a single-cycle infectious SARS-CoV-2 VRP system that serves as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high-throughput screening of antiviral drugs under BSL2 containment. IMPORTANCE Due to the highly contagious nature of SARS-CoV-2 and the lack of immunity in the human population, research on SARS-CoV-2 has been restricted to biosafety level 3 laboratories. This has greatly limited participation of the broader scientific community in SARS-CoV-2 research and thus has hindered the development of vaccines and antiviral drugs. By deleting the essential spike gene in the viral genome, we have developed a conditional mutant of SARS-CoV-2 with luciferase and fluorescent reporters, which can be safely used under biosafety level 2 conditions. Our single-cycle infectious SARS-CoV-2 virus replicon system can serve as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high-throughput screening of antiviral drugs under BSL2 containment.


FAS/FASL expression profile as a prognostic marker in squamous cell carcinoma of the oral cavity.
FAS/FASL altered expression may cause tumor protecting immunomodulation, with a direct impact on patient prognosis. FAS expression was studied in 60 squamous cell carcinomas of the oral cavity. FAS expression did not show a significant association with tumor histopathological characteristics, but was significantly associated with lymph node positivity. FAS expression was significantly associated with disease specific death and negative FAS expression was an independent risk factor, increasing risk 4 times when compared to positive expression. When FAS and FASL expression results were combined, we were able to define high, intermediate and low risk profiles. Disease-free and disease-specific survival were significantly correlated with FAS/FASL expression profiles. The high risk category was an independent marker for earlier disease relapse and disease-specific death, with approximately 4- and 6-fold increased risk, respectively, when compared to the low risk profile. Risk profiles based on FAS/FASL expression showed that high risk was significantly associated with increased disease relapse and death, as well as shorter disease-free or disease-specific survival. This categorization, added to patient clinical data, may facilitate the choice of therapy, minimizing treatment failure and increasing disease control.


Unique multiple paternity in the endangered big-headed turtle (Platysternon megacephalum) in an ex situ population in South China.
Understanding the mating system and reproductive strategies of an endangered species is critical to the success of captive breeding. The big-headed turtle (Platysternon megacephalum) is one of the most threatened turtle species in the world. Captive breeding and reintroduction are necessary to re-establish wild populations of P. megacephalum in some of its historical ranges in China, where the original populations have been extirpated. However, the captive breeding of P. megacephalum is very difficult and this may be due to its mysterious reproductive strategies and special behavior (e.g., aggressive temperament and territoriality). In this study, we achieved successful captive breeding of P. megacephalum by creating a habitat that mimics natural conditions and then investigated its mating system using microsatellite makers. A total of 16 clutches containing 79 eggs of P. megacephalum were collected, and 52 were hatched successfully over two breeding seasons. Of the 15 effective clutches, 6 clutches (40%) exhibited multiple paternity. There was no significant correlation between clutch size and multiple paternity, and no significant difference in hatching success between multiple-sired and single-sired clutches. However, there was significant correlation between male body size and the number of offspring, with higher-ranked males contributing to more clutches. Our results provide the first evidence of multiple paternity and male hierarchy in P. megacephalum. These findings suggest that multiple paternity and male hierarchy should be considered in captive breeding programs for P. megacephalum, and creating a habitat that mimics natural conditions is an effctive way to achieve successful captive breeding and investigate the mating systems of this species.


The dermatoglyphic characteristics of transsexuals: is there evidence for an organizing effect of sex hormones.
It has been proposed that gender identity and sexual orientation are influenced by the prenatal sex steroid milieu. Human dermatoglyphics and brain asymmetry have also been ascribed to prenatal hormone levels. This study investigated dermatoglyphics (total ridge count and finger ridge asymmetry) in 184 male-to-female transsexuals and 110 female-to-male transsexuals. In a subgroup, the relationship between dermatoglyphic asymmetry and spatial ability was tested. All investigations included controls. For all subjects hand preference and sexual orientation were noted. We hypothesized that the dermatoglyphics of male-to-female transsexuals would show similarities with control women and those of female-to-male transsexuals with control men. Our results showed a trend for a sex difference in total ridge count (P<.1) between genetic males and females, but no difference in directional asymmetry was found. Contrary to our expectations, the total ridge count and finger ridge asymmetry of transsexuals were similar to their genetic sex controls. Additionally, directional asymmetry was neither related to sexual orientation, nor to different aspects of spatial ability. In conclusion, we were unable to demonstrate that our chosen dermatoglyphic variables, total ridge count and finger ridge asymmetry are related to gender identity and sexual orientation in adult transsexuals. Hence, we found no support for a prenatal hormonal influence on these characteristics, at least insofar as dermatoglyphics may be regarded as a biological marker of organizing hormonal effects.


Sexual Trauma, Substance Abuse, and Treatment Success in a Sample of African American Women Who Smoke Crack Cocaine.
The purpose of this descriptive study was to examine the relationship among sexual trauma, severity of substance use, and treatment success for African American women who smoke crack cocaine. Using a convenience sample of 208 African American women with a history of crack smoking, participants were interviewed for 2 to 4 hr and asked a variety of questions about their health, relationships, sexuality, and drug use. Women with a history of sexual trauma (N = 134) reported being addicted to more substances than women who had not been sexually traumatized (N = 74), despite the fact that the two groups did not differ on the number of substances used. Differences in the self-reported level of substance abuse was corroborated with external evidence of group differences in substance abuse severity. Women with a history of sexual trauma, compared to women without such a history, were admitted to the hospital or emergency room more often for health issues related to their substance use and were more likely to be negligent in caring for their children because of their drug use. We also found evidence to suggest that there are differences in treatment success between the two groups; women with a history of sexual trauma reported having been to substance abuse treatment programs more often than women without such a history. These findings are discussed in light of the particular treatment needs of women with a history of sexual trauma.


Validation of fluorescent in situ hybridization combined with flow cytometry for assessing interindividual variation in the composition of human fecal microflora during long-term storage of samples.
This work was conducted to assess the accuracy of in situ hybridization to show differences in human microflora composition between volunteers and to optimize the storage of fecal samples to allow delayed analysis of gut microflora composition in humans. Fecal samples from 25 healthy subjects (14 women, 11 men aged 24-51) were collected. The samples were fixed in 4% Paraformaldehyde (PFA) solution at 4 degrees C overnight and stored at -70 degrees C. Twenty samples were analysed to quantify the variation due to interindividual differences in the composition of fecal microflora. The five remaining samples were stored either after PFA fixation or directly frozen at -70 degrees C and were monitored on a 12-month period. The fecal microflora was analysed by in situ hybridization combined with flow cytometry detection. Ribosomal RNA-targeted probes were used to assess the relative proportions of four phylogenetic groups: Clostridium coccoides-Eubacterium rectale (Erec 482), Bacteroides (Bac 303), Faecalibacterium prausnitzii (Fprau 645) and Bifidobacterium (Bif 164). Our results demonstrated that the method used is adapted to detect significant differences in fecal microflora composition in humans. Moreover, samples stored in PFA solution demonstrated a stable composition even after 8 months of storage. Conversely, frozen samples were less stable as the Bifidobacterium and C. coccoides-E. rectale groups showed significant differences after 2 months of storage. In conclusion, the fecal microflora composition can be analysed up to 8 months after 4% PFA fixation and storage at -70 degrees C. It represents an extended time compared with the 2-month period currently recommended. This will give more flexibility for applying this technology in epidemiological studies including a large number of samples.