Cost-effectiveness of Early Division of the Forehead Flap Pedicle.
The paramedian forehead flap is considered the gold standard procedure to optimally reconstruct major defects of the nose, but this procedure generally requires 2 stages, where the flap pedicle is divided 3 weeks following the initial surgery to ensure adequate revascularization of the flap from the surrounding recipient tissue bed, which can cost a patient time out of work or away from normal social habits. It has previously been shown that the pedicle may be safely divided after 2 weeks in select patients where revascularization from the recipient bed was confirmed using intraoperative laser fluorescence angiography to potentially save the patient time and money. To demonstrate the cost-effectiveness of takedown of the paramedian forehead flap pedicle after 2 weeks using angiography with indocyanine green (ICG). Retrospective cohort study of all patients who underwent 2-week division of the forehead flap after nasal reconstruction. Patient, tumor, defect, and outcomes data were collected. Cost-minimization analysis was performed by comparing the overall costs of 2-week takedown with angiography to a hypothetical patient undergoing 3-week takedown without angiography. Two-week division of the forehead flap after nasal reconstruction. Cost-minimization analysis performed by calculating the total variable costs for a patient in our cohort vs costs to a theoretical patient for whom angiography was not performed and the pedicle was divided at the 3-week mark. A total of 22 patients were included (mean [SD] age, 70.3 [10.0] years; 8 women [36.4%] and 14 men [63.6%]). The selection criteria for 2-week division of the pedicle are a wound bed with at least 50% vascularized tissue present, partial-thickness defects, and absence of nicotine use. All were divided at the 2-week mark with no instances of flap necrosis. One patient had a squamous eccrine carcinoma histology before reconstruction, all other patients had basal cell carcinoma, squamous cell carcinoma, and melanoma. Cost-minimization analysis showed that the use of angiography with ICG results in cost savings of $177 per patient on average. Two-week takedown of select paramedian forehead flap patients can be performed safely with verification using angiography with ICG. Although this technology inherently adds cost, it is cost-effective, saving a total of $177 per patient. NA.


A CD5+ B cell hybridoma derived factor(s), which induces maturation of CD5+, idiotype-specific B-cell populations.
A number of investigators have demonstrated the association of CD5+ (Ly-1/Leu-1) B cells with autoimmunity, excessive B-cell proliferation, and transformation. Previous work from our laboratory, among others, suggests that the selective advantage of this frequently autoreactive B-cell subset is to provide activation signals to conventional antigen-specific B cells. If one current hypothesis is correct then the overrepresentation of CD5+ B cells in some diseases and their novel capacity to act as helper cells reflect the activities of a separate B-cell lineage. Because of these observations it is of particular interest to evaluate the factors which contribute to the maturation of the CD5+ B-cell subset. The possibility that CD5+ B cells produce a factor or factors capable of influencing their own development was the focus of the present investigation. Rather than attempt to obtain soluble factors from heterogeneous CD5+ B-cell populations which could be contaminated with cytokine secreting monocytes or which could require as yet undefined activation signals in order to secrete putative factors, we chose to evaluate the production of CD5+ B-cell inducing factor(s) by monoclonal CD5+ B-cell hybridomas. Added incentive to this approach was provided by the observation that these hybridomas elaborate a factor(s) which, together with (NPb) idiotype-specific antibody produced by the hybridoma, substitutes for CD5+ B-cell populations in activating antigen-specific (NPb idiotypic) B cells in vitro. Furthermore, because of the low percentage of CD5+ B cells in the spleen and their relatively low level of CD5 antigen expression, we employed a sensitive functional assay rather than surface antigen expression alone to detect small numbers of mature CD5+ B helper cells. With this previously described system it was possible to observe the induction of functional CD5+ B cells following a 40 h culture of apparently CD5- B-cell populations with a 19-22 kd factor or factors derived from a CD5+ B hybridoma. Data presented here and elsewhere suggest that this CD5+ B-cell inducing activity is not mediated by IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, GM-CSF, or TNF. The role that such a B cell derived, B-cell directed factor may play in immunity and disease is discussed.


Genetics of anxiety disorders.
There is considerable evidence that genetic determinants play a major role in the etiology of anxiety. Investigations into susceptibility genes for anxiety are well underway, particularly for panic disorder and obsessive-compulsive disorder and more broadly defined anxiety-related traits, such as neuroticism and harm avoidance. This review will discuss some of the core issues related to diagnosis and molecular genetic methodology, followed by a review of recent molecular genetic findings for anxiety. The authors will attempt to highlight the numerous convergent and exciting findings. Given the rapid acceleration in knowledge of the human genome, a more definitive understanding of the genetic roots of these complex conditions may be anticipated in the relatively near future.


Self-encapsulating Poly(lactic-co-glycolic acid) (PLGA) Microspheres for Intranasal Vaccine Delivery.
Herein we describe a formulation of self-encapsulating poly(lactic-co-glycolic acid) (PLGA) microspheres for vaccine delivery. Self-healing encapsulation is a novel encapsulation method developed by our group that enables the aqueous loading of large molecules into premade PLGA microspheres. Calcium phosphate (CaHPO4) adjuvant gel was incorporated into the microspheres as a protein-trapping agent for improved encapsulation of antigen. Microspheres were found to have a median size of 7.05 ± 0.31 μm, with a w/w loading of 0.60 ± 0.05% of ovalbumin (OVA) model antigen. The formulation demonstrated continuous release of OVA over a 49-day period. Released OVA maintained its antigenicity over the measured period of >21 days of release. C57BL/6 mice were immunized via the intranasal route with prime and booster doses of OVA (10 μg) loaded into microspheres or coadministered with cholera toxin B (CTB), the gold standard of mucosal adjuvants. Microspheres generated a Th2-type response in both serum and local mucosa, with IgG antibody responses approaching those generated by CTB. The results suggest that this formulation of self-encapsulating microspheres shows promise for further study as a vaccine delivery system.


Lifestyle modification decreases arterial stiffness and plasma asymmetric dimethylarginine level in overweight and obese men.
Increased arterial stiffness is an independent risk factor for cardiovascular disease. Arterial stiffness is higher in obese individuals than in nonobese individuals. Lifestyle modifications (i.e. exercise and dietary modification) decrease arterial stiffness in obese individuals. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase, an enzyme responsible for the generation of nitric oxide. The aim of this study was to examine whether lifestyle modifications affect circulating levels of ADMA in overweight and obese men and, if they do, whether ADMA is involved in the mechanism underlying the decrease in arterial stiffness with lifestyle modification. Seventeen overweight and obese men (BMI: 29.8±0.8 kg/m(2)) completed a 12-week lifestyle modification program, which included aerobic exercise and dietary modification. Before and after the intervention, we evaluated brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, and plasma ADMA concentration in all participants. After the 12-week lifestyle modification program, BMI and baPWV decreased significantly and the plasma ADMA concentration decreased markedly in overweight and obese men. There was a significant positive correlation between percent change in baPWV and plasma ADMA concentration. Lifestyle modifications reduce arterial stiffness and plasma ADMA concentration in overweight and obese individuals. A decrease in arterial stiffness was associated with a corresponding reduction in plasma ADMA concentrations. These results suggest that reductions in ADMA may be an important mechanism underlying the beneficial effect of lifestyle modification on arterial stiffness.


Impaired semen quality associated with environmental DDT exposure in young men living in a malaria area in the Limpopo Province, South Africa.
The pesticide DDT [1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane] is 1 of the 12 persistent organic pollutants (POPs) under negotiation at the Stockholm Convention to restrict or ban their production and use because of their toxicity, resistance to breakdown, bioaccumulation, and potential for being transported over long distances. DDT has estrogenic potential, and the main metabolite, p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE), is a potent antiandrogen. In response to mounting evidence on the endocrine-disrupting influence of environmental chemicals on human health, this epidemiological study was initiated to test the hypothesis that nonoccupational exposure to DDT affects male reproductive parameters. In a cross-sectional study, healthy male subjects (n=311) between 18 and 40 years (23+/-5) of age were recruited from 3 communities in an endemic malaria area in which DDT is sprayed annually. A semen analysis according to World Health Organization (WHO) standards was performed. The Hamilton Thorne Computer Assisted Sperm Analysis (CASA) system was simultaneously used to determine additional sperm motility parameters. Blood plasma samples were assayed for p,p'-DDT and metabolites as a measure of exposure. The exposure levels were expressed as lipid-adjusted p,p'-DDT and p,p'-DDE values. The mean p,p'-DDT and p,p'-DDE concentrations were 90.23 microg/g(+/-102.4) and 215.47 microg/g(+/-210.6), respectively. The multivariate linear regression analyses indicated that mean CASA motility was lower with a higher p,p'-DDE concentration (beta=-0.02, P=.001) and the CASA parameter beat cross-frequency (BCF) was higher with a higher p,p'-DDT concentration (beta=0.01, P=.000). There was also a statistically significant positive association between percent sperm with cytoplasmic droplets and p,p'-DDT concentration (beta=0.0014, P=.014). The ejaculate volume (mean 1.9+/-1.33 mL) was lower than the normal range (>or=2.0 mL) according to WHO, and a significant decrease with increasing p,p'-DDE values was seen for both square root-transformed volume (beta=-0.0003; P=.024) and count (beta=-0.003; P=.04). Although there were no associations between either p,p'-DDT or p,p'-DDE concentrations and the rest of the seminal parameters, the incidence of teratozoospermia (99%; normal sperm<15%) was high. Twenty-eight percent of the study group presented with oligozoospermia (<20x10(6) sperm/mL), which had a significant positive association with p,p'-DDE (odds ratio [OR]=1.001, P=.03). There was a significant positive association between participants with asthenozoospermia (32%) and p,p'-DDT (OR 1.003, P=.006) and p,p'-DDE (OR 1.001, P=.02). The results imply that nonoccupational exposure to DDT is associated with impaired seminal parameters in men. The high exposure levels of p,p'-DDT and p,p'-DDE are of concern because these levels could have far-reaching implications for reproductive and general health.


Recent advances in cleanup of fats by sweep co-distillation. Part 1: Organochlorine residues.
A redesigned fractionation tube has resulted in development of a new, commercial sweep co-distillation unit. It is compact, reliable, cost-efficient, and permits cleanup of pesticides in up to 10 fat samples simultaneously. Recovery of several organochlorine residues (HCB, alpha-BHC, lindane, heptachlor epoxide, dieldrin, p,p'-DDE, p,p'-DDD, p,p'-DDT) at ppm and ppb levels in meat (beef) fat are 83-105%, with coefficients of variation between 4 and 6%. Cleaned up extracts are quantitated by gas chromatography using an electron capture detector with a vitreous silica capillary column containing a medium polarity bonded phase.


A compact high-voltage pulse generator based on pulse transformer with closed magnetic core.
A compact high-voltage nanosecond pulse generator, based on a pulse transformer with a closed magnetic core, is presented in this paper. The pulse generator consists of a miniaturized pulse transformer, a curled parallel strip pulse forming line (PFL), a spark gap, and a matched load. The innovative design is characterized by the compact structure of the transformer and the curled strip PFL. A new structure of transformer windings was designed to keep good insulation and decrease distributed capacitance between turns of windings. A three-copper-strip structure was adopted to avoid asymmetric coupling of the curled strip PFL. When the 31 microF primary capacitor is charged to 2 kV, the pulse transformer can charge the PFL to 165 kV, and the 3.5 ohm matched load can deliver a high-voltage pulse with a duration of 9 ns, amplitude of 84 kV, and rise time of 5.1 ns. When the load is changed to 50 ohms, the output peak voltage of the generator can be 165 kV, the full width at half maximum is 68 ns, and the rise time is 6.5 ns.


Treatment of vancomycin-resistant Enterococcus faecium infections with an investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of fifteen cases.
New therapies for vancomycin-resistant Enterococcus faecium (VREF) infections are urgently needed. We describe the treatment of 15 patients with VREF infection with quinupristin/dalfopristin (RP 59500), a new injectable streptogramin antibiotic. Primary infections treated were bacteremia (4), urinary tract (4), intraabdominal (5), otitis externa (1), and meningitis (1). Minimum inhibitory concentrations for quinupristin/dalfopristin ranged from 0.5 microgram/ml or less to 2 micrograms/ml, and minimum bactericidal concentrations were greater than 64 micrograms/ml for all VREF isolates tested. Peak serum inhibitory titers following infusion of quinupristin/dalfopristin ranged from 1:8 to 1:64; all bactericidal titers were less than 1:2. Development of resistance to quinupristin/dalfopristin during therapy was not observed. The only drug-related adverse effect noted was phlebitis in 4 patients; all had received quinupristin/dalfopristin by peripheral venous infusion. Three patients had clinical and bacteriologic cures. Relapses occurred in 5 patients with recovery of VREF from infected sites in post-treatment cultures. Ten patients died of severe underlying disease; VREF was believed to contribute directly to the death of only 1 patient. While evaluation of clinical efficacy was complicated by the severity of underlying disease in patients with VREF infection, our experience suggests that quinupristin/dalfopristin is a safe and potentially useful agent for the treatment of VREF infections.


Vulvar keratoacanthoma.
Keratoacanthomas are neoplastic proliferations of keratinocytes thought to originate from follicular epithelium. There is only one previously reported case in which keratoacanthoma involved the vulva. A 54-year-old woman presented with a nonulcerated vulvar lesion of approximately 1 month's duration. The lesion was 1 cm in diameter, located on the mid-right labium majus, with no surrounding induration or hyperkeratosis. The patient underwent wide local excision and the clinical-pathologic diagnosis was keratoacanthoma. After 2 years, she remains free of vulvar recurrence. Because of similarities in clinical presentation and histology to squamous cell carcinoma, the diagnosis of keratoacanthoma can be challenging. History and physical examination findings should be correlated with the histologic diagnosis, with consideration for dermatopathology consultation.


A study on malarial infection in HIV-infected individuals.
To find out whether malaria occurred at an increased frequency in HIV-infected individuals and to evaluate the clinical course and risk factors for malarial infection in HIV, a prospective study was carried out in a tertiary care centre from June, 1999 to December, 2000 among HIV-infected individuals with HIV-uninfected Individuals taken as control. In this study, out of 250 individuals, 152 were HIV-infected and the remaining were HIV-negative. The odd's ratio (OR) for the occurrence of malaria in the HIV-infected population compared with the HIV-uninfected population was 2.5 (95% confidence interval: 1.01, 6.4; p < 0.02). The prevalence of malaria in HIV infection was 20.4%. The same was 8.3% in asymptomatic stage, and 22.6% and 21.3% in the early and late symptomatic stages of HIV disease respectively. Among those who came for follow-up 44.4% of the HIV-infected individuals had recurrence of malarial infection. Contrary to what was thought before, malaria occurred at an increased frequency in HIV cases. The occurrence of malaria increased in the symptomatic stages of HIV disease compared to the asymptomatic stage. Recurrence was high in the HIV-infected population.


Dimer interface of glutathione S-transferase from Arabidopsis thaliana: influence of the G-site architecture on the dimer interface and implications for classification.
The three-dimensional structure of glutathione S-transferase from Arabidopsis thaliana has been solved at 2.2 A resolution (Reinemer et al., 1996). The enzyme forms a dimer of two identical subunits. The structure shows a new G-site architecture and a novel and unique dimer interface. Each monomer of the protein forms a separate G-site. Therefore, the requirements on the dimer interface are reduced. As a consequence, the interactions between the monomers are weaker and residues at the dimer interface are more variable. Thus, the dimer interface looses its relevance for a classification of plant glutathione S-transferases and the formation of heterodimers becomes even more difficult to predict.


Structure function analysis of novel type III polyketide synthases from Arabidopsis thaliana.
The genome sequencing project revealed presence of two active chalcone synthase (CHS) homologues (At1g02050 and At4g34850) in the model plant Arabidopsis thaliana. We report herein the two genes encode closely related novel plant-specific type III polyketide synthases (PKSs) that produces long-chain alkyl alpha-pyrones. PKS-A (At1g02050) and PKS-B (At4g34850) share significantly low amino acid sequence identity (20-40%) with other type III PKSs, and the phylogenetic tree analysis revealed that they form a separate cluster located closely to those of bacterial type III PKSs. When expressed in Escherichia coli, both PKS-A and PKS-B accepted unusually long (up to the C(20) chain-length) fatty acyl CoAs as a starter substrate, and carried out sequential condensations with malonyl-CoA to produce triketide and tetraketide alpha-pyrones. Interestingly, despite the low sequence identity, homology modeling revealed that the active-site architecture of PKS-A and PKS-B showed similarity to that of a bacterial type III PKS from Mycobacterium tuberculosis.


Effects of different iron supply to pregnant sows (Sus scrofa domestica L.) on reproductive performance as well as iron status of new-born piglets.
The present study aimed to investigate the effects of different iron (Fe) supply to sows during gestation on their reproductive performance and placental Fe load. Additionally, the Fe status of the corresponding offspring was assessed. Twenty multiparous sows were fed from insemination to farrowing with isoenergetic and isonitrogenic balanced diets differing in Fe content. The diet low in Fe (Group -Fe) was mainly composed of soybean meal and maize meal and had a Fe content of 114 mg/kg DM. For the diet high in Fe (Group +Fe), the diet was supplemented with Fe(II)SO4 · 7H2O to a total Fe content of 256 mg/kg. Blood characteristics (haemoglobin, haematocrit, mean corpuscular haem concentration, total Fe-binding capacity, transferrin saturation) of all sows were measured at the beginning and at the end of gestation. Daily Fe retention was calculated at the day of farrowing. After birth, reproductive performance (litter size, piglet weight, litter weight), placental Fe content and Fe blood characteristics of the piglets were determined. Apparent daily Fe retention tended to be greater in Group +Fe (p < 0.1). Blood parameters of the sows did not show any variations between feeding groups, neither at the beginning nor at the end of pregnancy, whereas placental Fe content was lower in Group -Fe (p < 0.05). In addition, Fe supply during gestation improved litter size (p < 0.01) and litter weight (p < 0.05). Although all sows were supplied according to the current Fe recommendations, a significant decline in reproductive performance of Group -Fe was recognised. Therefore, it was concluded that the re-evaluation of the gross Fe requirements of pregnant sows is inevitable to accommodate the current feeding recommendations.


[Foix-Alajouanine syndrome, what is it?].
The article contains the description of Foix-Alajouanine syndrome (FAS) from literature. Three our own cases of FAS, which developed in two men and one woman, are presented. An analysis of FAS clinical picture revealed a step-like progression of the disease with a possibility of short-term fluctuation of some focal neurological signs. Five stages of clinical course of FAS were detected. Some peculiar sings of spinal neurovisualization, together with serum and cerebro-spinal fluid (CSF) laboratory examinations, were indicated in FAS. Surgery is first-choice of FAS treatment. Pharmacological treatment with high doses of anticoagulants, together with antiviral therapy (and antibiotics, if necessary), neuroprotectors, antiedematic and symptomatic therapy must be started early. Prevention of thrombotic, trophic and purulent complications is required.


Photosynthetic activity of cyanobacteria in water-in-oil microemulsions.
The solubilization and the photosynthetic activity of cyanobacteria (Anabaena variabilis) in water-in-oil microemulsions consisting of (Tween85/Span80)/hexadecane/water is investigated. Transparent and stable solutions containing up to 10(8) cells/mL could be obtained. The physical state and stability of the cells in the microemulsion, as evidenced from optical and electron microscopy, is dependent upon the physical parameters of the system, and in particular on the hydrophilic-lypophilic balance (HLB) of the surfactant system. Conditions could be found, under which the cells in the microemulsion system display photosynthetic activity This was judged by measuring polarographically the oxygen evolution and by studying the photosynthetic activity in the presence of specific inhibitors.


Obstacles to Exercising Reproductive Rights for Single Women in China and Legal Recommendations.
Reproductive rights represent an intrinsic and pivotal human entitlement, encompassing legal protection for procreation. Essential to this framework is the recognition that single women equally deserve reproductive rights. Although Chinese legislation refrains from overtly disallowing reproductive rights for single women, the interplay of conventional marriage norms and family planning policies has inadvertently tied these rights to marital status, consequently constraining single women's ability to assert them. The establishment of a robust legal structure to ensure reproductive rights for single women would profoundly contribute to advancing a harmonious evolution of China's population dynamics. We employ meticulous textual scrutiny to analyze comprehensively the stipulations concerning women's reproductive liberties within the framework of Chinese jurisprudence. Furthermore, we engage in empirical inquiry to enumerate and elucidate the multifarious constraints placed upon the reproductive freedoms of unmarried women in the Chinese context. This endeavor entails a detailed exposition and incisive examination of China's limitations imposed upon the reproductive rights of single women, encompassing both legal strictures and policy dimensions. The absence of legal endorsement and safeguarding has given rise to substantial impediments to the exercise of reproductive rights among single women in China. Not only do endeavors to assert reproductive rights on behalf of single women encounter intricate challenges in judicial implementation, but they also encounter manifold barriers within national policies. This predicament not only subjects single women to considerable psychological strain but also contradicts the overarching objective of achieving a harmonized population development trajectory in China. China should expedite the development of a legal framework for protecting reproductive rights that includes provisions for supporting single women to have children. This legal apparatus should efficaciously enshrine and shield the reproductive rights of single women, thus playing a pivotal role in advancing a more equitable and well-balanced trajectory of population development.


New phenolic compounds from Dendrobium capillipes and Dendrobium secundum.
Phytochemical investigation of the stem of Dendrobium capillipes resulted in the isolation of a new flavonol glycoside namely quercetin-3-O-α-L-rhamnopyranosyl-(1 → 2)-β-d-xylopyranoside, along with seven known phenolic compounds which included two flavonol glycosides and five bibenzyls. From the stem of Dendrobium secundum, a new compound named 5-hydroxy-3,4,3',4',5'-pentamethoxybibenzyl was characterized, together with two known bibenzyls and three glycosidic flavonoids. Some of the isolated bibenzyls showed cytotoxicity against KB, NCI-H187, and MCF-7 cancer cells, whereas all of the glycosidic flavonoids were devoid of activity.


Interaction of temperature with other environmental factors in controlling the development of plants.
Development is the ordered sequence of changes in plant form and phenology that occurs through time. As such it is distinguished from that of growth and includes the succession of ontogenetic stages as well as the initiation of leaves, shoots and roots. It is more useful to look at rates of development as functions of environmental influences rather than, for example, total number of days to a given stage. It is often found that linear, or close to linear, relationships are found between rates and temperature, photoperiod and the duration of cold temperatures. These ideas are treated theoretically and illustrated with data from an experiment where wheat was grown at ten sites in Britain. We conclude that temperature is the most important factor governing differences in developmental rates between sites and sowing dates, especially for later stages of development. Variation in the timing of earlier stages depends on either exposure to photoperiods of different lengths or on the degree of vernalization of the plants. Calculation is made of the maximum effectiveness of these environmental factors in shortening the vegetative phases in a range of wheat cultivars and the basis of their interaction is also explored. For wheat it seems that they act multiplicatively in their effect on developmental rate. The rate at which plants produce their leaves is important in canopy development. The sensitivity of the rate of leaf emergence, measured in thermal time, has been linked to the rate at which daylength changes (d phi/dt). A possible mechanism may involve plants responding to the ratio of light in the red (R, ca 660 nm) and far-red (FR, ca 730 nm) wavebands (R/FR). This ratio decreases when d phi/dt is becoming more negative and vice versa. Linkage can be found between the change in R/FR at twilight and commensurate changes in calculated phytochrome photoequilibria. Thus, the possibility exists that phytochrome may be involved in modulating the leaf production rate in response to different sowing dates. Alternatively, variation in rate of leaf production may be through changes in the base temperature, in response to the 'spectrum' of temperatures the plants experience during development. Thus, any involvement of photoperiod in this response may be spurious. Controlled environment studies of leaf emergence tend to support this latter interpretation as does analysis of experiments from three European sites.


Changes in antenna of photosystem II induced by short-term heating.
Changes in antenna of photosystem II, induced by short-term heating, were studied using characteristics of a short-wavelength band in low-temperature fluorescence spectra (77 K) of pea chloroplasts. Heating for 5 min was carried out at 25 and 45°C in the darkness or in the presence of white light with intensity of 260 or 1,400 μmol/m(2)s. Most modes of thermal treating induced a decrease in integral intensity of the band and an increase of its half-width. The changes were more prominent at high-temperature heating. The second derivative of the contour of a short-wavelength band showed its three components around 680, 685, and 693 nm, the first of which belongs to emission of the outer antenna of Photosystem II, and the other two to its inner antenna. As the fourth derivative shows, high-temperature heating in the presence of light evokes an appearance of some additional components in a short-wavelength region (654, 658, 661, 666, 672, and 675 nm) as well as of two additional components, 682 and 689 nm, in the region of 685-nm peak. Two subcomponents, 692 and 694 nm, can be detected in the 693-nm component. The results are discussed on the basis of the data concerning energy levels and pathways of energy transfer in pigment-protein complexes of the outer and the inner antennas of photosystem II. It is assumed that a protective role of low light relates to inducing of an essential disarrangement in the outer and the inner antennas and of a subsequent decrease in energy funneling to reaction centers, which, in turn, lowers the extent of photoinhibition.


[Perforation of the colon by a foreign body].
Perforation of the colon carries a high mortality and morbidity. Perforations caused by foreign bodies are relatively rare and appear to be less often associated with postoperative complications than perforations due to organ disease. Depending upon the extent of the perforation and its anatomical site, as well as on the basis of the presence of diffuse or circumscribed peritonitis, the treatment of foreign-body perforation will vary from simple suturing, with or without a protective colostomy, to exteriorization in the form of a colostomy, and the Hartmann operation.


Rational Design of a Potent Pan-Pim Kinases Inhibitor with a Rhodanine-Benzoimidazole Structure.
The serine/threonine Pim kinases are overexpressed in various types of solid carcinomas and hematological malignancies, and contribute to regulating cell-cycle progression and cell survival. The aim of this study was to discover a novel pan-Pim kinases inhibitor with potent anti-proliferative activities against cancer cell lines. We screened a panel of small molecule compounds for their ability to inhibit Pim-1 kinase activity, and the hit compound was optimized using the docking analysis to Pim-1. We evaluated kinase-inhibition activities of the rationally-designed compound against Pim-1, 2, 3 and another five kinases. Furthermore, in order to characterize the cellular activities, both solid and hematological cancer cell lines treated with the compound were subjected to anti-proliferative assay, western blotting, FACS and apoptosis assays. We discovered a pan-Pim kinases inhibitor, compound 1, with a rhodanine-benzylidene structure via Pim-1 inhibitor screening. Using docking analysis of compound 1 and Pim-1, we optimized it and found a potent- and selective-Pim kinases inhibitor, compound 2, with a rhodanine-benzoimidazole structure. Compound 2 inhibited Pim-1, 2, 3 with IC50 values of 16, 13, and 6.4 nM, respectively, and suppressed proliferation of solid and hematological cancer cell lines at submicromolar concentrations. In both types of cell lines, compound 2 inhibited phosphorylation of Pim signaling substrates and cell-cycle progression and induced apoptosis. We identified a pan-Pim kinases inhibitor, compound 2, with a rhodanine-benzoimidazole structure. Our data suggest that compound 2 can serve as a lead to novel anticancer agents, effective in the treatment of both solid carcinomas and hematological malignancies.


Imaging of quantum array structures with coherent and partially coherent diffraction.
Recent achievements in experimental and computational methods open the possibility of measuring and inverting the diffraction pattern from a finite object of submicrometer size. In this paper the possibilities of such experiments for two-dimensional arrays of quantum dots are discussed. The diffraction pattern corresponding to coherent and partial coherent illumination of a sample was generated. Test calculations based on the iterative algorithms were applied to reconstruct the shape of the individual islands in such a quantum structure directly from its diffraction pattern. It is demonstrated that, in the case of coherent illumination, the correct shape and orientation of an individual island can be obtained. In the case of partially coherent illumination, the correct shape of the particle can be obtained only when the coherence of the incoming beam is reduced to match the size of the island.


Disruptions in standard care: anterior cruciate ligament reconstruction outcomes during the SARS-COV2 pandemic.
The SARS-COV2 pandemic led to massive disruptions of care for orthopedic patients. Although many elective procedures were put on hold, a cohort of patients who underwent surgery prior to the outbreak of the pandemic were rendered unable to participate in standard post-operative care. The purpose of this study was to determine the methods of post-operative care in arthroscopic anterior cruciate ligament reconstruction patients who received care during an early height of the pandemic to those who received standard of care in the prior year. We aimed to correlate those results with 1-year clinical outcomes in the form of subjective surveys. Retrospective chart review was used to identify patients who underwent primary anterior cruciate ligament reconstruction in February and March of 2020 (case) and 2019 (control) at a single institution. Workman's compensation patients were excluded. Identified patients were asked to report post-operative care received, satisfaction with care, and complete the IKDC and Lysholm outcome measures. Surveys were conducted minimum 1-year post-operative. 236 patients were identified, including 103 in 2020 and 133 in 2019. Follow-up data was collected for 73 patients (70.9%) in 2020 and 97 patients (72.9%) in 2019. Fifty-one COVID cohort patients (69.9%) had at least one clinical visit conducted via telehealth, compared to zero in the control. There were no differences in IKDC (82.8 ± 13.2 vs 85.0 ± 12.0, P = 0.29) and Lysholm (89.2 ± 11.3 vs 89.6 ± 10.8, P = 0.82) between groups. There were no differences in patient satisfaction with the care received (82.9 ± 22.4 vs 81.9 ± 21.8, P = 0.79). Despite disruptions in care, anterior cruciate ligament reconstruction patients have excellent 1-year outcomes during the pandemic. Telehealth follow-up appointments may be appropriate for anterior cruciate ligament reconstruction patients beyond the pandemic and do not seem to adversely affect short-term patient reported outcome measures.


Cooperative activation of gene expression by agonists and antagonists mediated by estrogen receptor heteroligand dimer complexes.
Estrogen receptor (ER) antagonists are generally thought to inhibit estrogen action through competitive inhibition, resulting in receptor binding to antagonist rather than agonist. However, microarray analyses reveal a group of genes for which ER agonist and antagonist cooperatively regulate expression, suggesting additional models of combined agonist/antagonist action must exist. In conjunction with a chimeric reporter gene and two modified ERs, one [ERα(GSCKV)] with a mutation in the DNA-binding domain and the other (ERα-G521R) with a ligand-binding specificity mutation, we herein demonstrate that ER agonist and antagonist cooperatively activate gene expression through an ER heteroligand dimer complex (ER-HLD) consisting of one subunit of the receptor dimer bound to agonist and another occupied by antagonist. Coimmunoprecipitation experiments confirmed interaction between the agonist-bound and antagonist-bound receptors. This cooperative activation of gene expression was enhanced by steroid receptor coactivator 3 coactivator, and required each ligand-bound subunit of the dimer to bind to DNA, as well as both activation function 1 domains for maximal transcriptional activity. Ligand combinations able to induce ER-HLD transcriptional activity include the agonists 17β-estradiol or conjugated estrogens with the antagonists tamoxifen, raloxifene, bazedoxifene, or fulvestrant. Moreover, ER-HLD can activate transcription in the context of a natural promoter. Taken together, these findings broaden our understanding of the complex relationship between ER agonist and antagonist, and suggest a novel model by which cell and tissue selective effects of antiestrogens may be achieved.


Oxidant-Antioxidant balance in patients with coronary slow flow.
Recent studies have focused on the probable role of oxidative stress in cardiovascular diseases. We aimed to assess the oxidant/antioxidant biomarkers in coronary slow flow (CSF). The study included 51 subjects with CSF and age and sex matched 32 controls. Detailed anamnesis of the patients in the study was taken and routine physical examinations were performed. Routine biochemical blood tests were analyzed. Total oxidative status (TOS), oxidative stress index (OSI) and lipid hydroxyperoxide (LOOH) levels as oxidant biomarkers; paraoxonase (PON1), ceruloplasmin (CP), free sulphydryl (SH) groups, and total antioxidant capacity (TAS) levels as antioxidant biomarkers were studied. Baseline demographic characteristics of the study population did not differ significantly between groups.TOS, OSI and LOOH concentrations were higher in study group than in control group. However, there was no significant difference detected in levels of TAS, PON1, SH and CP. Multivariate logistic regression analysis revealed that TOS, hsCRP and smoking were indepedent risk factors of CSF. Although there was not any significant difference in antioxidant biomarkers (TAS, PON1, SH and CP) in CSF patients, we detected increased TOS, OSI and LOOH levels which have oxidant properties. These data supported the possible involvement of oxidative stress in pathogenesis of CSF as previous studies reported.


New evidence on fluoridation.
A review of recent scientific literature reveals a consistent pattern of evidence--hip fractures, skeletal fluorosis, the effect of fluoride on bone structure, fluoride levels in bones and osteosarcomas--pointing to the existence of causal mechanisms by which fluoride damages bones. In addition, there is evidence, accepted by some eminent dental researchers and at least one leading United States proponent of fluoridation, that there is negligible benefit from ingesting fluoride, and that any (small) benefit from fluoridation comes from the action of fluoride at the surface of the teeth before fluoridated water is swallowed. Public health authorities in Australia and New Zealand have appeared reluctant to consider openly and frankly the implications of this and earlier scientific evidence unfavourable to the continuation of the fluoridation of drinking water supplies.


The structure of phosphine-functionalised silsesquioxane-based dendrimers: a molecular dynamics study.
Molecular dynamics modelling has been used to simulate the structures of phopshine-functionalised, silsesquioxane-based dendrimers whose excellent catalytic properties have been previously demonstrated. The effect of changing the chemical composition of the dendrimer branches is simulated. The results indicate that adding a methylene unit to a branch increases the overall size of the dendrimer but replacing a methylene unit with an oxygen atom decreases the size of the dendrimer. The size and shape of the dendrimers have also been simulated on changing the temperature and polarity of the solvent. The distribution of phosphine groups on the exterior has also been modelled and this suggests that all are available for bonding to catalytic metals in all the compounds.


Effect of anoxia on in vitro bladder function.
Previous studies have demonstrated that the ability of the in vitro whole bladder to empty in response to bethanechol administration was inhibited by anoxia while its ability to generate pressure decreased only slightly. One question was not addressed by these early studies: Is the anoxic effect selective for receptor-mediated contractile stimulation (as opposed to non-receptor-mediated contractile stimulation)? The present study was designed to compare the effect of anoxia on the ability of the in vitro bladder to generate pressure, sustain pressure, and empty in response to field stimulation (FS), bethanechol and KC1 administration. Each New Zealand white rabbit was anesthetized with pentobarbital and the bladder removed. The bladder was mounted as a whole-bladder preparation in a 300-ml isolated bath containing Tyrode's solution at 37 degrees C and equilibrated with 95% O2, 5% CO2. Anoxia was produced by changing the gas mixture to 95% nitrogen, 5% CO2. The effect of anoxia on the response to FS, bethanechol, and KCl was determined at different times after the initiation of anoxia. The results of these studies can be summarized as follows. (1) Anoxia induced a time-dependent decrease in the rate of pressure generation, the magnitude of pressure generation, and the percent volume emptied in response to FS and bethanechol. (2) At all time periods of anoxia, the ability of the bladder to empty was inhibited to a significantly greater degree than either the rate of magnitude of pressure generation (for both FS and bethanechol administration).(ABSTRACT TRUNCATED AT 250 WORDS)


Protective Immune Responses Generated in a Murine Model Following Immunization with Recombinant Schistosoma japonicum Insulin Receptor.
There is a pressing need to develop vaccines for schistosomiasis given the current heavy dependency on praziquantel as the only available drug for treatment. We previously showed the ligand domain of the Schistosoma japonicum insulin receptor 1 and 2 (rSjLD1 and 2) fusion proteins conferred solid protection in mice against challenge infection with S. japonicum. To improve vaccine efficacy, we compared the immunogenicity and protective efficacy of rSjLD1 on its own and in combination with S. japonicum triose-phosphate isomerase (SjTPI), formulated with either of two adjuvants (QuilA and montanide ISA 720VG) in murine vaccine trials against S. japonicum challenge. The level of protection was higher in mice vaccinated only with rSjLD1 formulated with either adjuvant; rSjTPI or the rSjTPI-rSjLD1 combination resulted in a lower level of protection. Mirroring our previous results, there were significant reductions in the number of female worms (30⁻44%), faecal eggs (61⁻68%), liver eggs (44⁻56%), intestinal eggs (46⁻48%) and mature intestinal eggs (58⁻63%) in the rSjLD1-vaccinated mice compared with the adjuvant only groups. At 6-weeks post-cercarial challenge, a significantly increased production of interferon gamma (IFNγ) in rSjLD1-stimulated splenic CD4⁺ T cells was observed in the rSjLD1-vaccinated mice suggesting a Th1-type response is associated with the generated level of protective efficacy.


The contamination of winter stores and early spring honey with spores of Paenibacillus larvae larvae in Polish apiaries of the Małopolska province.
We analysed 251 early spring and winter storage honey samples, individually collected from the apiaries of 9 districts of Malopołska province in South Poland and revealed that 51 of these specimens were contaminated with different levels of P. larvae larvae spores Among these samples 8.8% were classified as a category I contamination and 11.5% as a category II--reperesenting 22 (43.1%) and 29 (56.9%) of the total positives, respectively. We conclude from these analyses that: (1)--the total number of new outbreaks of AFB in Poland are most likely to be higher than previously reported, (2)--the quantitative examination of samples of winter stored or early spring honeys for the presence of P. larvae, larvae spores can improve the detection rate of AFB outbreaks, (3)--the high percentage of apiaries that were found to be free of P. larvae larvae (80%) may facilitate the implementation of an AFB eradication programme on a large scale in Poland.


Effect of a low salt diet on blood pressure and vasoactive hormones in the hereditary hypertriglyceridemic rat.
In hereditary HTG rats, basal systolic blood pressure using tail-cuff sphygmomanometry was significantly higher (122.1 +/- 2.1 mm Hg; n = 16) than that in NTG animals (107.1 +/- 1.52; n = 16). A low salt diet did not influence blood pressure in NTG rats during the consecutive 4 weekly periods. However, in the second week blood pressure in HTG rats rose significantly in both the control rats on a normal salt diet and those on a low salt diet (132.5 +/- 1.89, n = 8, and 132.6 +/- 1.93, n = 8). No further changes were registered in the third and fourth week in control HTG rats. On the other hand, blood pressure fell significantly in HTG rats on a low salt diet in the third week in comparison with the second week (119.5 +/- 3.2, n = 8), and it increased again in the fourth week (123.0 +/- 2.35, n = 8). Hormones in plasma were determined at the end of the experiment. Plasma levels of norepinephrine were not influenced by differences in salt intake and were significantly higher by about 45% in HTG than in NTG animals. The lowest concentration of corticosterone in plasma was found in control HTG rats (1.2 +/- 0.2 vs 4.6 +/- 0.8 micrograms/100 ml in control NTG rats). Nevertheless, corticosterone concentration increased in HTG rats on a low salt diet at comparable values found in NTG rats on a low salt diet (3.1 +/- 0.8 vs 4.3 +/- 1.5). Plasma renin activity and plasma aldosterone concentrations were not different in the NTG and HTG groups and were uninfluenced by the diets (Table 1). We conclude that the elevated blood pressure in HTG rats and its variations during the experiment may reflect more pronounced sympathetic activity in HTG rats rather than blood pressure dependency on different salt intake.


Clinical features and treatment of drug fever caused by anti-tuberculosis drugs.
Tuberculosis is a major global health problem. However, anti-tuberculosis drug treatment has many adverse effects, such as drug-caused fever. The aim of this study was to investigate the clinical features and treatments of anti-tuberculosis drugs-induced fever. A total of 78 inpatients and outpatients with pulmonary tuberculosis accompanied by drug fever during the anti-tuberculosis treatment were analysed retrospectively from April 2006 to March 2013. Among the anti-tuberculosis drugs that caused the drug fever, rifampicin was the most common one, followed by para-aminosalicylic and pyrazinamide. The symptoms occurred within 2 months after treatment, mainly in the 1-3 weeks, and the main symptom was high fever with body temperature above 39°C. The accompanying symptoms include rash, chills, headache, stuffy nose, runny nose, nausea, vomiting and joint pain. Routine blood examination found that eosinophilia increased in 15 cases and decreased in another 15. Among 63 patients who underwent liver function tests, there were 10 cases of abnormal function and 4 cases of liver damage. When the drug fever was suspected, the measure of withdrawal was taken first. All the suspected drugs were withdrawn in 59 cases, while gradual withdrawal was conducted in 19 cases. Patients with complications were first treated in accordance with the principles of complications treatment and then were gradually given some drugs after recovery. The patients without complications were gradually given some drugs after the body temperature was back to normal. Drug fever is an allergic reaction, the resolution of which depends on whether it was accompanied by liver damage and/or rash or not.


Services for people with complex psychosis: towards a new understanding.
This paper describes the need for commissioners and service providers to consider the development of a whole-system approach to providing rehabilitation services for patients with complex psychosis, in the context of the current economic pressures and emergence of a competitive market in this area of mental health. The practical and organisational arrangements for the management of risk with such services are described, taking into account the varying provision of rehabilitation services across the UK and considering how these can be developed against the care clustering system and interfaces with other mental health services.


Synthesis and phase evolutions in layered structure of Ga2S3 semiconductor thin films on epiready GaAs (111) substrates.
We report on synthesis and properties of p-type Ga2S3 semiconductor thin films that were prepared by sulfurizing epiready n-type GaAs (111) surface at elevated temperatures. Comparisons of structural and optical properties among the thin films, peeling-off resulted microtubes, and the remains after peeling-off give a clear clue to the crystal growth and phase evolutions of Ga2S3. Three layers of Ga2S3 are clearly identified in the thin films. They are layer i, cubic Ga2S3 epitaxially grown on the GaAs (111) substrate; layer ii, polycrystalline cubic Ga2S3 on top of layer-i; and layer iii, monoclinic and/or hexagonal Ga2S3 on top of layer ii. The onset of peeling-off occurred in layer i and/or at the interface between layer i and ii. Both the phase evolutions and the location of peeling-off are associated with a Ga out diffusion growth mechanism. Absorption spectroscopy revealed a direct bandgap of 3.0 eV, whereas photoluminescence spectra showed defects (excited Ga vacancies) related red (1.62 eV) and green (2.24 eV) emissions of the Ga2S3 films; both are qualitatively consistent with those reported values obtained at lower sample temperatures from Ga2S3 single crystals. These results, together with a large on/off current ratio (i.e., ∼14 at a bias of 4.0 V) of the resultant hetero p-Ga2S3/n-GaAs junction under a blue laser (405 nm, 3.0 mW) illumination, shed light on consequent integrations of Ga2S3- and GaAs-based optoelectronic devices, e.g., high-power laser radiation sensors.


Presence of Meaning in Life and Search for Meaning in Life and Relationship to Health Anxiety.
The present study explored presence of meaning in life, search for meaning in life, and their correlation with health anxiety. The Meaning in Life Questionnaire and the Short Health Anxiety Inventory were completed by 753 individuals. Results indicated higher presence of meaning in life was associated with lower health anxiety, while the opposite was observed for search for meaning in life. Results also revealed an interaction between presence of meaning in life and search for meaning in life, where individuals with high search for meaning in life and high presence of meaning in life had lower health anxiety than those with high search for meaning in life and low presence of meaning in life. These findings suggest that presence of meaning in life and search for meaning in life are correlates of health anxiety.


A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3.
A large Danish family has previously been reported in which autosomal dominant frontotemporal dementia (FTD) is genetically linked to chromosome 3 (FTD-3). A mutation was recently identified in the CHMP2B gene that is probably responsible for causing disease in this family. Because of its neuropathologic findings, FTD-3 was originally categorized as a subtype of frontotemporal lobar degeneration, termed "dementia lacking distinctive histopathology." We now report a reevaluation of the neuropathologic changes in this family. Postmortem material from 4 affected family members was available for examination. Gross examination revealed generalized cortical atrophy that was most severe in frontal and temporal cortices. Microscopy showed loss of cortical neurons, microvacuolation of layer II, mild gliosis, and demyelination of the deep white matter. Results of immunohistochemical staining for alpha-synuclein, prion protein, neurofilament, and tau protein were unremarkable. Variable numbers of small, round, ubiquitin-positive cytoplasmic inclusions were present in the dentate granule layer of the hippocampus in all 4 cases. Rare ubiquitin-positive inclusions were also found in frontal and temporal cortical neurons. These inclusions were also positive for p62 but not for TDP-43. The finding of ubiquitin- and p62-positive, TDP-43-negative cytoplasmic inclusions in the hippocampus and neocortex suggests reclassification of the neuropathology of FTD-3 as a unique subtype of frontotemporal lobar degeneration with ubiquitin-positive inclusions that are TDP-43-negative.


A Simple Method for the Cross-Section Area Determination of Single Profiled Fibers and Its Application.
One of the critical prerequisites for accurately measuring the mechanical properties of profiled fibers is the precise determination of their cross-sectional areas (CSAs). In this study, a new method is established for determining a single profiled fibers' CSA based on the frozen section method and digital photo, pixel-ratio method (FS-DP). FS-DP is used to obtain a transverse section of a fiber, by acquiring an image of the cross section using optical microscopy or scanning electron microscopy, and then calculating the CSA using Photoshop. Using FS-DP, it was found that the shape of a fiber of silk changes little in a range of 50 μm, but varies considerably over a range of 1 m, while the CSA of cocoon silk (900 m) first increases and then decreases. Mechanical property tests showed that the elongation, strength, elastic modulus, and toughness values of the cocoon silk are consistent with those reported previously. Additionally, FS-DP was also used to observe other profiled fibers. The application tests indicated that FS-DP can be used to quickly and accurately obtain the CSA of a single profiled fiber, and that it is suitable for the large-scale determination and analysis of the mechanical properties of profiled fibers.


Measuring nucleus mechanics within a living multicellular organism: Physical decoupling and attenuated recovery rate are physiological protective mechanisms of the cell nucleus under high mechanical load.
Nuclei within cells are constantly subjected to compressive, tensile, and shear forces, which regulate nucleoskeletal and cytoskeletal remodeling, activate signaling pathways, and direct cell-fate decisions. Multiple rheological methods have been adapted for characterizing the response to applied forces of isolated nuclei and nuclei within intact cells. However, in vitro measurements fail to capture the viscoelastic modulation of nuclear stress-strain relationships by the physiological tethering to the surrounding cytoskeleton, extracellular matrix and cells, and tissue-level architectures. Using an equiaxial stretching apparatus, we applied a step stress and measured nucleus deformation dynamics within living Caenorhabditis elegans nematodes. Nuclei deformed nonmonotonically under constant load. Nonmonotonic deformation was conserved across tissues and robust to nucleoskeletal and cytoskeletal perturbations, but it required intact linker of nucleoskeleton and cytoskeleton complex attachments. The transition from creep to strain recovery fits a tensile-compressive linear viscoelastic model that is indicative of nucleoskeletal-cytoskeletal decoupling under high load. Ce-lamin (lmn-1) knockdown softened the nucleus, whereas nematode aging stiffened the nucleus and decreased deformation recovery rate. Recovery lasted minutes rather than seconds due to physiological damping of the released mechanical energy, thus protecting nuclear integrity and preventing chromatin damage.


Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer.
Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer. Consecutive patients with locally advanced (T2 ≥ 4 cm-T4 or N+) anal cancer scheduled for two cycles of concomitant 5-fluorouracil and mitomycin C chemotherapy were selected from an institutional database (n = 106). All received intensity modulated radiotherapy (IMRT; mean dose primary tumor 59.5 Gy; mean dose elective lymph nodes 45.1 Gy). Clinical data were extracted from medical records. The highest-grade WBC toxicity was recorded according to CTCAE version 5.0. Pelvic bone marrow (PBM) was retrospectively contoured and dose-volume histograms were generated. The planning CT was used to measure sarcopenia. Dosimetric, anthropometric, and clinical variables were tested for associations with WBC G3+ toxicity using the Mann-Whitney test and logistic regression. Cox proportional hazard regression was used to assess predictors for overall survival (OS) and anal cancer specific survival (ACSS). WBC G3+ was seen in 50.9% of the patients, and 38.7% were sarcopenic. None of the dosimetric parameters showed an association with WBC G3+ toxicity. The most significant predictor of WBC G3+ toxicity was sarcopenia (adjusted OR 4.0; P = 0.002). Sarcopenia was also associated with an inferior OS (adjusted HR 3.9; P = 0.01), but not ACSS (P = 0.07). Sensitivity analysis did not suggest that the inferior prognosis for sarcopenic patients was a consequence of reduced doses of chemotherapy or a prolonged radiation treatment time. Patients who experienced WBC G3+ toxicity had an inferior OS and ACSS, even after adjustment for sarcopenia. Sarcopenia was associated with increased risks of both WBC G3+ toxicity and death following CRT for locally advanced anal cancer. In this study, radiation dose to PBM was not associated with WBC G3+ toxicity. However, PBM was not used as an organ at risk for radiotherapy planning purposes and doses to PBM were high, which may have obscured any dose-response relationships.


Detoxification of aflatoxin B1 and patulin by Enterococcus faecium strains.
Aim of the present study was to investigate the detoxification of aflatoxin B(1) and patulin from aqueous solution by probiotic culture of Enterococcus faecium M74 and commercial culture of E. faecium EF031. The effect of the bacterial viability, incubation time and pH of the medium on the binding ability was tested. Also, binding stability was determined by washing the bacteria-mycotoxin complexes with phosphate buffer saline. Both M74 and EF031 strains have the ability to remove aflatoxin B(1) and patulin. While M74 removes 19.3 to 30.5% of aflatoxin B(1) and 15.8 to 41.6% of patulin, EF031 removes 23.4 to 37.5% of aflatoxin B(1) and 19.5 to 45.3% of patulin throughout a 48 h incubation period. The removal of aflatoxin B(1) and patulin was highest at pH 7.0 and 4.0, respectively. The stability of the aflatoxin B(1) and patulin complexes formed with the bacterial strains was found to be high. The viability of the bacteria did not have any significant effect on the detoxification of aflatoxin B(1) and patulin. Detoxification properties of E. faecium could represent new strategies for a possible application in the human diet and animal feed.


Exploratory, cognitive, and depressive-like behaviors in adult and pediatric mice exposed to controlled cortical impact.
Sequelae of behavioral impairments associated with human traumatic brain injury (TBI) include neurobehavioral problems. We compared exploratory, cognitive, and depressive-like behaviors in pediatric and adult male mice exposed to controlled cortical impact (CCI). Pediatric (21 to 25 days old) and adult (8 to 12 weeks old) male C57Bl/6 mice underwent CCI at a 2-mm depth of deflection. Hematoxylin and eosin staining was performed 3 to 7 days after recovery from CCI, and injury volume was analyzed using ImageJ. Neurobehavioral characterization after CCI was performed using the Barnes maze test (BMT), passive avoidance test, open-field test, light/dark test, tail suspension test, and rotarod test. Acutely and subacutely (3 and 7 days after CCI, respectively), CCI mice showed graded injury compared to sham mice for all analyzed deflection depths. Time-dependent differences in injury volume were noted between 3 and 7 days following 2-mm TBI in adult mice. In the BMT, 2-mm TBI adults showed spatial memory deficits compared to sham adults (P<0.05). However, no difference in spatial learning and memory was found between sham and 2-mm CCI groups among pediatric mice. The open-field test, light/dark test, and tail suspension test did not reveal differences in anxiety-like behaviors in both age groups. Our findings revealed a graded injury response in both age groups. The BMT was an efficient cognitive test for assessing spatial/non-spatial learning following CCI in adult mice; however, spatial learning impairments in pediatric mice could not be assessed.


Combination of DYRK2 and TERT Expression Is a Powerful Predictive Marker for Early-stage Breast Cancer Recurrence.
DYRK2 is a dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase induces degradation of telomerase reverse transcriptase (TERT). The expression of both proteins in breast cancer were investigated as predictors of recurrence. Two hundred and twenty-one patients with early breast cancer treated at our institute between 2000 and 2009, were included. We used immunohistochemical analyses to measure the expression of DYRK2 and TERT and correlated it with clinicopathological factors and survival. DYRK2 and TERT were positive in 58 (26%) and 86 (39%) of 221 patients, respectively. There was no correlation between DYRK2 and TERT expression and clinicopathological factors. Better disease-free survival was observed in the DYRK2-positive group (p=0.032), and poorer disease-free survival was noted in the TERT-positive group (p=0.023). The DYRK2-positive TERT-negative group exhibited significantly better disease-free survival than the other groups (p=0.006). The combination of DYRK2 and TERT may be a powerful tool to stratify breast cancer patients.


Effects of moderate-intensity light on vitamin A-deficient rat retinas.
The effects of moderate-intensity light (150 to 200 ft-cd) on retinal structure were compared between retinol-adequate and retinol-deficient rats after 1 to 6 days of light exposure during the 12 hr light phase of the cycle. Both damage to the outer segments and loss of photoreceptor cells were accelerated in retinol-adequate rats. Outer segments in retinas of retinol-adequate rats showed an abnormal staining pattern and disruption of disc structure in the distal portion about 2 days before those of retinol-deficient rats. After 4 days of exposure 24% of the photoreceptor cells had degenerated in the retinol-adequate retinas, but only 6% in the retinol-deficient retinas. By 6 days 65% and 41% of the photoreceptors had degenerated in the retinol-adequate and retinol-deficient retinas, respectively. Thus light exposure induced more rapid degeneration of photoreceptor cells in rats receiving adequate retinol than in those deficient in this vitamin.


Blocking activity of rat monoclonal antibodies in experimental schistosomiasis.
Rat IgG2c monoclonal antibodies have been produced after fusion of spleen cells from LOU/C rats infected with Schistosoma mansoni for 5 wk and IRF983F nonsecreting rat myeloma. The cell supernatant of an IgG2c-producing clone (IPLSm3), as well as ascitic fluids induced by this clone, revealed anti-S. mansoni activity detected by immunofluorescence on schistosomula sections. Antigenic analysis performed with IPLSm3 IgG2c antibody allowed to isolate onto the S. mansoni schistosomula surface a 38,000 dalton antigen previously characterized with the protective IPLSm1 IgG2a monoclonal antibody. Although IPLSm3 IgG2c did not exhibit any killing activity in vitro against schistosomula in the presence of complement, macrophages, or eosinophils, it was shown to strongly inhibit the eosinophil-dependent cytotoxicity mediated by IPLSm1 IgG2a antibodies. The blocking activity of IgG2c antibody was further demonstrated in vitro by the use of F(ab')2 fragments and in vivo by the inhibition of passively transferred immunity conferred by the IgG2a protective monoclonal antibody. These results indicate that blocking antibodies could play an important role in the expression of protective immunity during schistosome infection.


Inhibition of mTOR signaling by rapamycin protects photoreceptors from degeneration in rd1 mice.
Retinitis pigmentosa (RP) is an inherited retinal degenerative disease that begins with defective rod photoreceptor function, followed by impaired cone function, and complete blindness in its late stage. To date, however, there is no effective treatment for RP. By carrying a nonsense mutation in the Pde6b gene, rd1 mice display elevated cGMP in conjunction with higher intracellular Ca 2+ in their rod photoreceptors, resulting in fast retinal degeneration. Ca 2+ has been linked to activation of the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway integrates extracellular and intracellular signals to sense the supply of nutrients and plays a central role in regulating protein and lipid synthesis as well as apoptosis and autophagy. In the present study, we showed that mTOR and phosphorylated mTOR (p-mTOR, activated form of mTOR) are up-regulated in rd1 photoreceptors at postnatal day 10 (P10), a pre-degenerative stage. Moreover, the downstream effectors of mTOR, such as pS6K and S6K, are also increased, suggesting activation of the mTOR signaling pathway. Intravitreal administration of rapamycin, a negative regulator of mTOR, inhibits the mTOR pathway in rd1 photoreceptors. Consequently, the progression of retinal degeneration is slower and retinal function is enhanced, possibly mediated by activation of autophagy in the photoreceptors. Taken together, these results highlight rapamycin as a potential therapeutic avenue for retinal degeneration.


Recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches .
To report a case of recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches. The patient was investigated using cerebral computed tomography, magnetic resonance imaging, cerebrospinal fluid examination, and electroencephalography. Written informed consent was obtained from the patient for access to clinical files for research purposes and publication. We present a middle-aged woman with two recurrent episodes of aseptic meningitis after treatment with trimethoprim-sulfamethoxazole. Additionally, she developed myoclonic twitches as a rare side effect of ampicillin. Aseptic meningitis is a rare adverse reaction to medications like antibiotics. The pathogenesis of trimethoprim-sulfamethoxazole-induced aseptic meningitis is not yet completely understood, but an immune-mediated hypersensitivity reaction is suspected. If patients with an antibiotic therapy due to a systemic or local infection present with severe headache, not only common diagnosis of a parainfectious headache, but also antibiotic-induced aseptic meningitis should be considered. .


Relationship Between Weight Status and Health-Related Quality of Life in School-age Children in China.
Background: Some studies from high-income countries suggest that overweight and/or obesity in children are negatively associated with health-related quality of life (HRQOL). However, the relationship between weight status and HRQOL is not well established in China, where obesity trends follow a different pattern compared with high-income countries. The risk of obesity is greater in children from higher socioeconomic backgrounds and higher in boys compared with girls. Objective: The aim of this study was to examine the relationship between weight status and HRQOL in children between 6 and 7 years old in this unique country context. Methods: Baseline HRQOL and demographic data were collected from children recruited to the CHIRPY DRAGON obesity prevention trial in China. HRQOL was measured using the Chinese version of the Child Health Utility-9D (CHU-9D-CHN) and the Pediatric Quality of Life Inventory™ (PedsQL™) instruments. CHU-9D-CHN utility scores were generated using 2 scoring algorithms (UK and Chinese tariffs). Height and weight measures were taken at school by trained researchers using standardized methods, and BMI z scores were calculated using the World Health Organization 2007 growth charts. The relationship between HRQOL and weight status was examined using multivariable analyses, adjusting for age, gender, and socioeconomic status. Results: Full data were available for 1539 children (mean age, 6 years). In both unadjusted and adjusted analyses, HRQOL, using both the CHU-9D-CHN and the PedsQL™, was marginally higher in children who were overweight or living with obesity compared with children with healthy weight, although this difference did not reach statistical significance. Separate analyses and models by gender showed that the relationship between weight status and HRQOL scores was similar in boys and girls. Conclusions: Our results suggest no statistically significant difference in HRQOL between children with overweight/obesity compared with those with healthy weight. These results have implications for the methods of economic evaluation for obesity treatment and prevention interventions within this population cohort and country setting, as there appears to be no discernible consequences on children's HRQOL from living with overweight and obesity.


Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer.
A large group of transcription factors regulating cell growth and differentiation share a dimeric alpha-helical DNA-binding domain termed the basic region helix-loop-helix (bHLH). bHLH proteins associate as homodimers and heterodimers having distinctive DNA-binding activities and transcriptional activities that are central to the regulated differentiation of a number of tissues. Some of the bHLH residues specifying these activities have been identified, but a full understanding of their function has awaited further structural information. We report here the crystal structure of the transcription factor E47 bHLH domain bound to DNA. The bHLH of E47 is a parallel, four-helix bundle with structural features that distinguish it from the bHLH-zipper protein Max. The E47 dimer makes nonequivalent contacts to each half of the -CACCTG- binding site. Sequence discrimination at the center of the E box may result from interaction with both the DNA bases and the phosphodiester backbone.


Expression of NEDD4-1, a PTEN regulator, in gastric and colorectal carcinomas.
Recent studies have disclosed that NEDD4-1 regulates PTEN activity by ubiquitination. NEDD4-1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4-1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4-1 in PTEN regulation in cancer cells, expression of NEDD4-1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4-1 expression in colorectal and gastric cancer tissues. We investigated NEDD4-1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4-1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4-1. There was no significant association of NEDD4-1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4-1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4-1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4-1 expression may play a role in colorectal and gastric cancer development.


Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances.
There has been a resurgence of interest in nanoemulsions for various pharmaceutical applications since low-energy emulsification methods, such as spontaneous or self-nanoemulsification, have been described. Self-nanoemulsifying drug delivery systems (SNEDDS) are anhydrous homogenous liquid mixtures consisting of oil, surfactant, drug and coemulsifier or solubilizer, which spontaneously form oil-in-water nanoemulsion of approximately 200 nm or less in size upon dilution with water under gentle stirring. The physicochemical properties, drug solubilization capacity and physiological fate considerably govern the selection of the SNEDDS components. The composition of the SNEDDS can be optimized with the help of phase diagrams, whereas statistical experimental design can be used to further optimize SNEDDS. SNEDDS can improve oral bioavailability of hydrophobic drugs by several mechanisms. The conversion of liquid SNEDDS to solid oral dosage forms or solid SNEDDS has also been achieved by researchers. Solid SNEDDS can offer better patient compliance and minimize problems associated with capsules filled with liquid SNEDDS.


Inferior Vena Cava Thrombus Associated With Renal Cell Carcinoma With an Atypical Radiological Presentation: A Case Report.
Renal cell carcinoma (RCC) is characterized by the development of kidney masses, which can lead to various long-term complications. Among the extrarenal manifestations associated with RCC, the formation of a thrombus within the inferior vena cava (IVC) is particularly prevalent due to the substantial tumor burden imposed by the kidneys. In this report, we present an exceptional case involving an 80-year-old male patient who presented with an intravascular thrombus within the inferior vena cava (IVC), which originated from RCC. The diagnosis of RCC was conclusively established through core needle biopsy and subsequent tumor marker staining. Remarkably, despite the confirmation of RCC within the IVC thrombus through biopsy and tumor marker analysis, radiological assessments failed to reveal any discernible renal cell masses within the kidneys. The patient subsequently received treatment for RCC with a combination regimen of cabozantinib and nivolumab, which resulted in a noteworthy improvement in his clinical condition. The presentation of RCC in this report is notably atypical, given that the biopsy of the thrombus yielded definitive evidence of RCC while radiological investigations did not yield any indications of renal masses or a tumor burden within the kidneys that would typically be associated with RCC.


Conserved and species-specific transcription factor co-binding patterns drive divergent gene regulation in human and mouse.
The mouse is widely used as system to study human genetic mechanisms. However, extensive rewiring of transcriptional regulatory networks often confounds translation of findings between human and mouse. Site-specific gain and loss of individual transcription factor binding sites (TFBS) has caused functional divergence of orthologous regulatory loci, and so we must look beyond this positional conservation to understand common themes of regulatory control. Fortunately, transcription factor co-binding patterns shared across species often perform conserved regulatory functions. These can be compared to 'regulatory sentences' that retain the same meanings regardless of sequence and species context. By analyzing TFBS co-occupancy patterns observed in four human and mouse cell types, we learned a regulatory grammar: the rules by which TFBS are combined into meaningful regulatory sentences. Different parts of this grammar associate with specific sets of functional annotations regardless of sequence conservation and predict functional signatures more accurately than positional conservation. We further show that both species-specific and conserved portions of this grammar are involved in gene expression divergence and human disease risk. These findings expand our understanding of transcriptional regulatory mechanisms, suggesting that phenotypic divergence and disease risk are driven by a complex interplay between deeply conserved and species-specific transcriptional regulatory pathways.


Predicting changes in perceived health status.
Panel data from the Los Angeles Health Survey (N = 903) were used to examine variables associated with changes in perceived health status over a one-year period. Our findings replicate previous research showing that perceived health status is associated with variations in chronic illness, disability, and the utilization of health services. However, we found that neither positive nor negative changes in perceived health status were related to any indicator of health beliefs or practices or physical health status. The data suggest that single item measures of perceived health status may reflect the individual's sense of long-standing chronic illness.


Lewis(y) antigen promotes the progression of epithelial ovarian cancer by stimulating MUC1 expression.
MUC1 is a type I transmembrane glycoprotein and is overexpressed in various epithelial tumor tissues. Some researchers have demonstrated that the glycosylation status of MUC1 can affect MUC1-mediated tumor growth and cell differentiation. In our previous study, we proved that the abilities of cell proliferation, adhesion, invasion and metastasis, and drug resistance were enhanced in ovarian cancer cells stably expressing Lewis(y). Therefore, we hypothesized that Lewis(y) antigen may play a central role in regulating MUC1 expression, and MUC1-mediated cell growth and differentiation may be closely associated with Lewis(y) antigen. This study aimed to examine the correlation between MUC1 expression and Lewis(y) antigen levels in ovarian cancer cell lines and tissue samples. A series of techniques, including RT-qPCR, western blot anlaysis, immunoprecipitation, immunohistochemistry and double-labeling immunofluorescence were applied to detect the expression of Lewis(y) and MUC1. In malignant epithelial ovarian tumors, the positive expression rates of Lewis(y) antigen and MUC1 were 88.33 and 86.67%, respectively, which were markedly higher than those in borderline (60.00 and 53.33%, P<0.05), benign (33.33 and 30%, P<0.01) and normal (0 and 25%, P<0.01) ovarian samples. There was no correlation between the positive expression rates of Lewis(y) or MUC1 and clinicopathological parameters in ovarian cancers (P>0.05). The expression levels of Lewis(y) and MUC1 correlated with the clinical FIGO stage (P<0.05). Both MUC1 and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P<0.01). In α1,2-fucosyltransferase (α1,2-FT)-transfected cells, the gene and protein expression levels of MUC1 were significantly upregulated compared with the cells that did not overexpress α1,2-FT (P<0.05). The ratio of Lewis(y) immunoprecipitated with MUC1 to total MUC1 increased 1.55-fold in α1,2-FT-overexpressing cells (P<0.05). The overexpression of Lewis(y) resulted in the upregulation of MUC1. On the whole, our data indicate that both MUC1 and Lewis(y) are associated with the occurrence and development of ovarian cancers.


Nifedipine attenuates acute hypoxic pulmonary vasoconstriction in awake piglets.
The calcium channel blocker nifedipine was administered to awake piglets to determine the drug's potential efficacy as a pulmonary vasodilator in newborns. We hypothesized that nifedipine attenuates acute hypoxic pulmonary vasoconstriction in this age group. Hemodynamic and arterial blood gas measurements were made in 24 catheterized piglets, 10 +/- 3 days of age, while they breathed room air and then 12% O2, 4% CO2, and 86% N2 gas. Thirteen piglets were studied before and after infusions of 15 and 40 micrograms X kg-1 X min-1 of nifedipine prior to hypoxia to see if the drug prevents hypoxic pulmonary vasoconstriction. In 7 animals, nifedipine was administered after the onset of hypoxia to see if the drug reduces ongoing hypoxic pulmonary vasoconstriction. Nifedipine significantly increased heart rate (56 +/- 28%) and cardiac output (48 +/- 45%) and decreased systemic artery pressure (-11 +/- 7%) and systemic vascular resistance (-37 +/- 18%) compared with pretreatment values under normoxic conditions. Pulmonary artery pressure increased (28 +/- 21%) after nifedipine treatment, but total pulmonary resistance remained unchanged during normoxia. Nifedipine did not reduce pulmonary artery pressure compared with pretreatment values during hypoxia, but reduced the elevation in total pulmonary resistance associated with hypoxia by 45 to 99% in a dose-dependent manner. We conclude that nifedipine vasodilates the constricted pulmonary vasculature associated with hypoxia in newborns but that this effect is manifested primarily by a rise in cardiac output rather than by a reduction in pulmonary artery pressure in this age group.


[A study of the cardiotocograms recorded by a separated 1MHz ultrasound transducer].
Fetal heart rate records were obtained in 12 antepartum and 13 intrapartum cases, with an ultrasonic Doppler transducer with five separated crystals and a conventional transducer. The loss of the FHR record due to increased noise in 30 minutes before delivery ranged from 1.1 to 23.2% (6.4 +/- 6.5%) in the separate type transducer, and it was 0.6 to 29.9% (10.5 +/- 7.6%) in the conventional one. During the 5 minutes before delivery, it was 3.3 to 58.0% (20.2 +/- 18.5%) in the separate type, and 3.3 to 70.0% (31.6 +/- 19.5%) in the conventional one. Clearer FHR records were obtained with the use of the separate type than the conventional one (p less than 0.05). Noise was mostly recorded in the 5 minutes before delivery. In the NST, the loss of the FHR record due to maternal posture change decreased when the new transducer (p less than 0.05) was used. The loss was 0 to 56.7% (14.9 +/- 18.2%) with the new type, and 2.0 to 100% (42.9 +/- 36.4%) with the conventional one for the maternal posture which showed the worst record. By using the separate type transducer, maternal posture need not to be limited in the NST, and the somatic and mental discomfort is less than when the conventional one is used.


Synthesis of N-tosylaziridines from substituted alkenes via zirconooxaziridine catalysis.
Herein we report the zirconooxaziridine promoted aziridination of alkenes using chloramine T as the quantitative source of N. The reaction works with high yields, diastereoselectivities and stereospecificity for a wide variety of substituted alkenes. A potential mechanism involving the formation of a zirconooxaziridine complex as the active catalyst has been proposed and initial mechanistic data would indicate that a highly associative mechanism is the predominant pathway for this transformation.


G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance.
Strand transfer inhibitors (raltegravir, elvitegravir and dolutegravir) are now commonly used to inhibit HIV-1 integration. To date, three main pathways conferring raltegravir/elvitegravir resistance, involving residues Y143, Q148 and N155, have been described. However, no pathway has been clearly described for dolutegravir resistance. The aim of this study was to characterize the susceptibility of two mutations, F121Y and G118R, originally described in patients failing raltegravir-containing regimens, to dolutegravir and raltegravir, and then to compare the resistance of these mutations with that of other well-known mutations involved in raltegravir resistance. Both the F121Y and G118R mutations were introduced by site-directed mutagenesis into the pNL4.3 backbone and studied in cell-based and in vitro assays. The effects of the mutations were characterized at the different steps of infection by quantitative PCR. Results obtained with in vitro and ex vivo assays consistently showed that both mutations impaired the catalytic properties of integrase, especially at the integration step. Moreover, both mutations conferred an intermediate level of resistance to dolutegravir. Interestingly, the F121Y mutation, but not the G118R mutation, displayed differential resistance to raltegravir and dolutegravir. Indeed, the F121Y mutation was more resistant to raltegravir than to dolutegravir. Mutations at G118 and F121, which have been described in patients failing raltegravir-containing regimens, must be included in drug-resistance-testing algorithms.


User-centered design of a scalable, electronic health record-integrated remote symptom monitoring intervention for patients with asthma and providers in primary care.
To determine user and electronic health records (EHR) integration requirements for a scalable remote symptom monitoring intervention for asthma patients and their providers. Guided by the Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework, we conducted a user-centered design process involving English- and Spanish-speaking patients and providers affiliated with an academic medical center. We conducted a secondary analysis of interview transcripts from our prior study, new design sessions with patients and primary care providers (PCPs), and a survey of PCPs. We determined EHR integration requirements as part of the asthma app design and development process. Analysis of 26 transcripts (21 patients, 5 providers) from the prior study, 21 new design sessions (15 patients, 6 providers), and survey responses from 55 PCPs (71% of 78) identified requirements. Patient-facing requirements included: 1- or 5-item symptom questionnaires each week, depending on asthma control; option to request a callback; ability to enter notes, triggers, and peak flows; and tips pushed via the app prior to a clinic visit. PCP-facing requirements included a clinician-facing dashboard accessible from the EHR and an EHR inbox message preceding the visit. PCP preferences diverged regarding graphical presentations of patient-reported outcomes (PROs). Nurse-facing requirements included callback requests sent as an EHR inbox message. Requirements were consistent for English- and Spanish-speaking patients. EHR integration required use of custom application programming interfaces (APIs). Using the NASSS framework to guide our user-centered design process, we identified patient and provider requirements for scaling an EHR-integrated remote symptom monitoring intervention in primary care. These requirements met the needs of patients and providers. Additional standards for PRO displays and EHR inbox APIs are needed to facilitate spread.


Lower urinary tract dysfunctions in women with diabetes mellitus.
This review discusses published data of the recent advances in understanding lower urinary tract dysfunctions in women with diabetes mellitus. Many studies have shown a relationship between diabetes mellitus and lower urinary tract dysfunctions. Although the pathophysiology of these disorders is multifactorial, microvascular damage and neuropathy causing dysfunctions of smooth muscle, urothelium, and neuronal components in the lower urinary tract are the most likely etiologies. Lower urinary tract dysfunctions are common in diabetes mellitus. Screening and effective management of these disorders should be promoted in an effort to decrease morbidity and improve quality of life.


Glucose tolerance in rats with elevated circulating prolactin levels.
The consideration of prolactin as one of the anti-insulin hormones has been based on studies describing the ability of injected prolactin to raise the serum glucose. We studied the glucose tolerance of rats made hyperprolactinemic by the implantation of extra anterior pituitary glands under the kidney capsule. Surprisingly the hyperprolactinemic rats had lower serum glucose levels after a bolus injection of dextrose. Furthermore, their serum insulin levels were no higher than sham-operated control rats. AFter a fast of 18 or 24 hours, the serum glucose was lower in the hyperprolactinemic rats, and the serum insulin concentrations were similar in implanted and control rats. These data suggest that chronic hyperprolactinemia does not decrease glucose tolerance. Whether prolactin has a direct insulin-like effect or whether it may potentiate insulin's effects will require further study.


Nikolskiy's sign revisited.
This article presents the original description of Nikolskiy's sign given by Piotr Vasiliyevich Nikolskiy in 1894, along with various different interpretations of Nikolskiy's sign and numerous terminologies used in the literature by a number of clinicians.


Studies on the biochemistry of the brain during aging.
There is little doubt that aging changes occur in specific brain cells and neural pathways. Since some of these changes occur in short-lived rodents which probably have no major vascular pathology [48], there may be a general phenomenon of aging in the brain neurotransmitter functions in short- and long-lived mammals. It remains to be discovered how the genome regulates the changes in catecholamine neurotransmitter functions and, further, how these changes relate to normal and pathologic age changes.


Mesenchymal stem cells in rheumatology: a regenerative approach to joint repair.
The advent of biologics in rheumatology has considerably changed the evolution and prognosis of chronic inflammatory arthritis. The success of these new treatments has contributed to steering more attention to research focussed on repair and remodelling of joint tissues. Indeed, when the tissue damage is established, treatment options are very limited and the risk of progression towards joint destruction and failure remains high. Increasing evidence indicates that mesenchymal stem cells persist postnatally within joint tissues. It is postulated that they would function to safeguard joint homoeostasis and guarantee tissue remodelling and repair throughout life. Alterations in mesenchymal stem cell biology in arthritis have indeed been reported but a causal relationship has not been demonstrated, mainly because our current knowledge of mesenchymal stem cell niches and functions within the joint in health and disease is very limited. Nonetheless, mesenchymal stem cell technologies have attracted the attention of the biomedical research community as very promising tools to achieve the repair of joint tissues such as articular cartilage, subchondral bone, menisci and tendons. This review will outline stem-cell-mediated strategies for the repair of joint tissues, spanning from the use of expanded mesenchymal stem cell populations to therapeutic targeting of endogenous stem cells, resident in their native tissues, and related reparative signals in traumatic, degenerative and inflammatory joint disorders.


From proficiency to expert, when does the learning curve for robotic-assisted prostatectomies plateau? The Columbia University experience.
To describe our single-institution experience with our first 70 consecutive robotic-assisted laparoscopic prostatectomies (RLPs) with particular focus on effect of learning curve on operative time, length of stay and blood loss. We also report our short-term outcome data in this heterogeneous cohort of men with prostate cancer (PCa). We reviewed our institutional database for the first 70 consecutive RLPs performed by a single surgeon (DS) over a 21-month period (March 2003 to December 2004). Surgical, pathologic and postoperative outcomes were analyzed. In order to evaluate the impact of the surgeon's and institution's learning curve on outcomes, the cases were divided into quartiles and stratified accordingly to identify trends. Ninety-nine percent (69/70) of all procedures were successfully completed robotically. Mean blood loss, operative time and mean length of stay were 231 ml, 264 min and 1.9 days, respectively. At follow-up, 76% of all patients were fully continent (no pads) and 93% (62/67) had undetectable PSA. The most dramatic improvement in surgical outcomes was seen within the first quartile of cases; however a statistically significant improvement trend existed throughout the series. This included a downward trend in operative time (P < 0.00001), estimated blood loss (P < 0.00001), and length of hospital stay (P = 0.003). This trend continued when controlled for in a multivariate analysis. Our results compare favorably with other RLP series as well as conventional laparoscopic series. Proficiency is achieved within the first 20 cases; however surgical outcomes continue to improve for RLP throughout the first 70 cases and perhaps beyond.


Sexuality as a treatment issue with a special population of adolescents.
The handicapped adolescent population heretofore has not been properly identified or serviced. These adolescents have to deal with body image and sexual identity problems. Working with the adolescent individually, in groups, and in a therapeutic community setting, we have developed methods of dealing with the issue of sexuality.


Semisynthesis of the native sequence of horse heart cytochrome c-(66-104)-nonatriacontapeptide.
The syntheses of some derivatives of horse cytochrome c-(66-79)-tetradecapeptide are presented. The syntheses are so designed that analogues of this phylogenetically well preserved sequence can be obtained also. The compounds were intended as synthons for the semisynthesis of 65-homoserine-cytochrome c, which we described earlier. A requisite for this project was the C-terminal tetracosapeptide fragment of the protein, accessible through degradation of cytochrome c with cyanogen bromide. The five epsilon amino groups in this compound are reversibly protected with the 2-(methylsulfonyl)ethyloxycarbonyl function, which is resistant to acid and causes little impairment of solubility. The condensation of the fragments leading to the native sequence of horse cytochrome c-(66-104)-nonatriacontapeptide is presented also. The syntheses were performed using the solution strategy. Some unexpected ring closing reactions involving tyrosine and tert.-butyl prolylasparaginylcarbazate, are described.


Cis-acting pathways selectively enforce the non-immunogenicity of shed placental antigen for maternal CD8 T cells.
Maternal immune tolerance towards the fetus and placenta is thought to be established in part by pathways that attenuate T cell priming to antigens released from the placenta into maternal blood. These pathways remain largely undefined and their existence, at face value, seems incompatible with a mother's need to maintain a functional immune system during pregnancy. A particular conundrum is evident if we consider that maternal antigen presenting cells, activated in order to prime T cells to pathogen-derived antigens, would also have the capacity to prime T cells to co-ingested placental antigens. Here, we address this paradox using a transgenic system in which placental membranes are tagged with a strong surrogate antigen (ovalbumin). We find that although a remarkably large quantity of acellular ovalbumin-containing placental material is released into maternal blood, splenic CD8 T cells in pregnant mice bearing unmanipulated T cell repertoires are not primed to ovalbumin even if the mice are intravenously injected with adjuvants. This failure was largely independent of regulatory T cells, and instead was linked to the intrinsic characteristics of the released material that rendered it selectively non-immunogenic, potentially by sequestering it from CD8α(+) dendritic cells. The release of ovalbumin-containing placental material into maternal blood thus had no discernable impact on CD8 T cell priming to soluble ovalbumin injected intravenously during pregnancy, nor did it induce long-term tolerance to ovalbumin. Together, these results outline a major pathway governing the maternal immune response to the placenta, and suggest how tolerance to placental antigens can be maintained systemically without being detrimental to host defense.


Resilience of Key Biological Parameters of the Senegalese Flat Sardinella to Overfishing and Climate Change.
The stock of the Senegalese flat sardinella, Sardinella maderensis, is highly exploited in Senegal, West Africa. Its growth and reproduction parameters are key biological indicators for improving fisheries management. This study reviewed these parameters using landing data from small-scale fisheries in Senegal and literature information dated back more than 25 years. Age was estimated using length-frequency data to calculate growth parameters and assess the growth performance index. With global climate change there has been an increase in the average sea surface temperature along the Senegalese coast but the length-weight parameters, sex ratio, size at first sexual maturity, period of reproduction and condition factor of S. maderensis have not changed significantly. The above parameters of S. maderensis have hardly changed, despite high exploitation and fluctuations in environmental conditions that affect the early development phases of small pelagic fish in West Africa. This lack of plasticity of the species regarding of the biological parameters studied should be considered when planning relevant fishery management plans.