Courting and noncourting male red-sided garter snakes, Thamnophis sirtalis parietalis: plasma melatonin levels and the effects of pinealectomy.
Previous studies found that pinealectomy of male Canadian red-sided garter snakes (Thamnophis sirtalis parietalis) in the autumn, before prolonged exposure to low temperatures (hibernation), significantly impaired the expression of courtship behavior upon emergence in the spring. Additionally, pinealectomized animals with a disrupted diel cycle of plasma melatonin did not court while those exhibiting a more typical diel pattern did. These results suggested that the pineal gland functions in the transduction of a temperature cue which stimulates courtship. To test this hypothesis, we pinealectomized males in the spring after they had undergone a normal hibernation but were still courting. Pinealectomy of courting males in the spring, in each of the 3 years of study, had no effect on courtship. This result suggests that once the cue is transduced, the pineal gland no longer has a modulatory effect on courtship behavior. Finally, we took advantage of the fact that, in the laboratory, there is always a small percentage of males that do not court upon emergence. Pinealectomy of these noncourters greatly increased the percent of males expressing courtship behavior in each of the study years. Plasma melatonin levels of unmanipulated courting and noncourting males was measured after emergence in successive years. In both years, courters had a typical pattern of melatonin secretion (low in the photophase, high in the scotophase) while persistent noncourters displayed the opposite pattern.


Prevalence of birth defects and parental work in Singapore live births from 1994 to 1998: a population-based study.
The aims of the study were to assess the prevalence of birth defects (BDs) among different occupational groups and non-working parents, and to identify possible risk factors associated with BDs in Singapore live births born between 1 January 1994 and 31 December 1998. To do this, information on live births (from the Singapore National Registry of Births and Deaths) and BD cases [from the National Birth Defects Register (NBDR)] was obtained from 1 January 1994 to 31 December 1998. There were a total of 237 755 live births in Singapore between 1 January 1994 and 31 December 1998. Over the same period, 3293 cases of BDs were reported to the NBDR, giving an overall rate of 13.9 per 1000 live births. A downward trend with time was noted. Of the live born with BDs in this series, 36.7% presented with multiple anomalies. The overall occurrence of malformation (per 1000 live births) among working versus non-working mothers was 13.4 versus 14.2, respectively, and 13.8 for working fathers compared with 16.8 for non-working fathers. Parents in the occupational group 'Legislators, Senior Officers & Managers' had the lowest prevalence rates of congenital anomalies (9.4 per 1000 for mothers and 10.3 per 1000 for fathers), while the 'Agricultural & Fishery Workers' had the highest rates (40.0 per 1000 for mothers and 23.4 per 1000 for fathers). However, the very small number of workers in this latter group makes the rate unreliable. The prevalence of BDs in Singapore is comparable to those in other countries. Parental work per se is not correlated with BDs.


Cinnamaldehyde Could Reduce the Accumulation of Diarrhetic Shellfish Toxins in the Digestive Gland of the Mussel Perna viridis under Laboratory Conditions.
Diarrhetic shellfish toxins (DSTs), some of the most important phycotoxins, are distributed almost all over the world, posing a great threat to human health through the food chain. Therefore, it is of great significance to find effective methods to reduce toxin accumulation in shellfish. In this paper, we observed the effects of four phytochemicals including cinnamaldehyde (CA), quercetin, oridonin and allicin on the accumulation of DSTs in the digestive gland of Perna viridis after exposure to the DSTs-producing Prorocentrum lima. We found that, among the four phytochemicals, CA could effectively decrease the accumulation of DSTs (okadaic acid-eq) in the digestive gland of P. viridis. Further evidence demonstrated that CA could reduce the histological alterations of the digestive gland of a mussel caused by DSTs. RT-qPCR showed that CA could suppress the CYP3A4 induction by DSTs, suggesting that the DSTs' decrease induced by CA might be related to the inhibition of CYP3A4 transcription induction. However, further studies on the underlying mechanism, optimal treatment time, ecological safety and cost should be addressed before cinnamaldehyde is used to decrease the accumulation of DSTs in field.


Analysis of the classical phase space and energy transfer for two rotating dipoles with and without external electric field.
We explore the classical dynamics of two interacting rotating dipoles that are fixed in the space and exposed to an external homogeneous electric field. Kinetic energy transfer mechanisms between the dipoles are investigated by varying both the amount of initial excess kinetic energy of one of them and the strength of the electric field. In the field-free case, and depending on the initial excess energy, an abrupt transition between equipartition and nonequipartition regimes is encountered. The study of the phase space structure of the system as well as the formulation of the Hamiltonian in an appropriate coordinate frame provide a thorough understanding of this sharp transition. When the electric field is turned on, the kinetic energy transfer mechanism is significantly more complex and the system goes through different regimes of equipartition and nonequipartition of the energy including chaotic behavior.


[Clinical analysis of tuberous sclerosis complex complicated with renal angiomyolipoma: a report of 22 cases].
To explore the diagnosis and treatment of tuberous sclerosis complex complicated with renal angiomyolipoma. The clinical data of 22 patients with tuberous sclerosis complex complicated with renal angiomyolipoma were analyzed retrospectively. There were 12 males and 10 females with a mean age of 23 (1-46) years. All of them had bilateral multiple renal angiomyolipomas. The mean tumor size was 8.5 (0.7-18.0) cm in diameter. The presence or absence of clinical symptoms showed a significant correlation with tumor size.Eight patients with angiomyolipoma under 4 cm in diameter were continuously monitored at an outpatient clinic. There were 8 patients with lesions of 4-10 cm.Five of them underwent nephron-sparing surgeries and another 3 monitored at an outpatient clinic. There were 6 patients with tumor over 10 cm. Three of them underwent transcatheter arterial embolization and one case took rapamycin after embolization.One patient with concurrent renal cell carcinoma underwent partial nephrectomy. Chronic renal failure occurred in one case dying of pulmonary lymphangiomyomatosis with serious hemoptysis. During a mean follow-up of 25 months, neither severe renal hemorrhage nor symptomatic aggravation was found.In the case of rapamycin, there was 10% reduction in the size of angiomyolipoma. Most cases of tuberous sclerosis complex are complicated with bilateral multiple renal angiomyolipoma. The small lesions under 4 cm in diameter may be monitored at an outpatient clinic.For those larger (>4 cm) or symptomatic ones, medication, embolization or surgery is necessary.


The role of aromatic side-chains in amyloid growth and membrane interaction of the islet amyloid polypeptide fragment LANFLVH.
Human islet amyloid polypeptide (hIAPP) is known to misfold and aggregate into amyloid deposits that may be found in pancreatic tissues of patients affected by type 2 diabetes. Recent studies have shown that the highly amyloidogenic peptide LANFLVH, corresponding the N-terminal 12-18 region of IAPP, does not induce membrane damage. Here we assess the role played by the aromatic residue Phe in driving both amyloid formation and membrane interaction of LANFLVH. To this aim, a set of variant heptapeptides in which the aromatic residue Phe has been substituted with a Leu and Ala is studied. Differential scanning calorimetry (DSC) and membrane-leakage experiments demonstrated that Phe substitution noticeably affects the peptide-induced changes in the thermotropic properties of the lipid bilayer but not its membrane damaging potential. Atomic force microscopy (AFM), ThT fluorescence and Congo red birefringence assays evidenced that the Phe residue is not required for fibrillogenesis, but it can influence the self-assembling kinetics. Molecular dynamics simulations have paralleled the outcome of the experimental trials also providing informative details about the structure of the different peptide assemblies. These results support a general theory suggesting that aromatic residues, although capable of affecting the self-assembly kinetics of small peptides and peptide-membrane interactions, are not essential either for amyloid formation or membrane leakage, and indicate that other factors such as β-sheet propensity, size and hydrophobicity of the side chain act synergistically to determine peptide properties.


Assessing risk of sexually abusive behavior among youth in a child welfare sample.
Statutory management of juvenile sexual offenders demands reliable, valid methods for assessing the risk posed by these youth. This study examined the predictive validity of the J-SOAP-II using samples of adolescent and pre-adolescent boys who were wards of the Massachusetts Department of Social Services. The base rate for sexual recidivism among the adolescents (14-16%) is generally in line with what has been reported. The equivalent base rate for the pre-adolescents (25-28%), however, was notably higher. Although the J-SOAP-II was developed for adolescents, the scale also worked with the pre-adolescents in predicting sexual recidivism over 7 years, with AUC values of 0.77, 0.74, 0.77, and 0.80 for Scales 1, 3, 4, and Total among the pre-adolescents and AUC values of 0.80, 0.82, and 0.83 for Scales 1, 4, and Total among the adolescents. Discussion focuses on extant J-SOAP research and sample dependent variability, as well as social policy implications.


Norwood procedure for hypoplastic left heart syndrome associated with valvular pulmonary stenosis.
Association between hypoplastic left heart syndrome and valvular pulmonary stenosis is very rare. Severity of valvular pulmonary stenosis in this setting limits management options. Consequently, patients with this condition are considered poor candidates for Norwood stage one reconstruction. Herein, we describe a newborn with hypoplastic left heart syndrome and significantly dysplastic pulmonary valve who successfully underwent the Norwood procedure with neoaortic valve reconstruction. Therefore, the Norwood procedure with neoaortic valve reconstruction might be an option for this difficult condition.


Effector B cells in cardiac allograft vasculopathy.
B cells have recently emerged as important immune players in solid organ rejection, especially in cardiac allograft vasculopathy (CAV), a chronic form of rejection following heart transplantation. B cells can exert either regulatory or effector functions. This review will provide an update on effector B cells in CAV. Independent studies reported the abundance of B cells in graft infiltrates during CAV, especially around coronary arteries. Infiltrates comprise CD20+ CD27+ memory B cells together with differentiated CD20-CD138+ plasma cells, which are almost always associated with T cells and macrophages. The structure of some of these infiltrates evokes that of germinal centers, suggesting the generation of tertiary lymphoid organs in the graft. Remarkably, B-cell infiltrates are most often detected in the absence of circulating donor human leukocyte antigen-specific antibodies, strongly suggesting that the two components are unrelated. Characterization of B-cell clones isolated from explanted human cardiac graft infiltrates revealed the prevalence of polyreactive innate, B1-like B cells. Accumulating evidence suggests that these cells act primarily as antigen-presenting cells in situ. Additional effector functions, such as local antibody secretion and pro-inflammatory cytokine production, promoting T-cell polarization, macrophage activation and fibrosis are also considered. Converging observations made through animal and human studies add substantial support for an effector B-cell role in the pathophysiology of CAV. On the basis of these collective findings, a therapeutic strategy targeting B cells could reasonably be envisaged to prevent or treat this complication.


Achieving a given reflectance for unpolarized light by controlling the incidence angle and the thickness of a transparent thin film on an absorbing substrate: application to energy equipartition in the four-detector photopolarimeter.
At a given wavelength lambda we determine all possible solution pairs (?, zeta) of the incidence angle ? and the thickness zeta of a transparent thin film on an absorbing substrate that achieve a given unpolarized light reflectance R(u). The trajectory of the point that represents a solution pair in the zeta, ? plane depends on the optical properties of the film and substrate and on whether R(u) is greater than or less than the normal-incidence reflectance -R(0) of the bare substrate. When R(u) > - R(0), the specified reflectance is achieved over a limited range of ?. At the least possible incidence angle, the film thickness is approximately ? th wave. As an application we consider SiO(2) films on Si detectors that produce R(u). = 0.75, 0.6667, and 0.50 at lambda = 337 and 633 nm. If the first three detectors of the four-detector photopolarimeter (FDP) are coated to have these reflectance levels, with the reflectance diminishing in the direction of propagation of the light beam, and the last detector is antireflection coated (e.g., with a quarter-wave Si(3)N(4) layer), equipartition of energy among the four detectors is accomplished for incident unpolarized light. Such a condition is desirable in the operation of the FDP. The ellipsometric parameters of the coated surfaces and the FDP instrument matrix are also calculated.


Diabetes-Related Stigma and its Influence on Social Networks, Social Support, and HbA1c in Ghana.
We applied a social network approach to examine if three types of diabetes-related stigma (self-stigma, perceived stigma and enacted stigma) moderated associations between social network characteristics (network size, kin composition, household composition, and network density), social support, and blood glucose among Ghanaians with type 2 diabetes mellitus (T2DM). Data were obtained through a cross-sectional survey of 254 adults at a diabetes clinic in Ghana that assessed participants' social networks, social support, and frequency of experiencing three types of diabetes-related stigma. Self-stigma moderated associations between kin composition and social support when controlling for network size β=-.97, P=.004). Among study participants reporting low self-stigma, kin composition was positively associated with social support (β=1.29, P<.0001), but this association was not found among those reporting high self-stigma. Network size was positively associated with social support among participants reporting both low and high self-stigma. None of the types of diabetes-related stigma moderated other associations between social networks, social support, and blood glucose. Individuals with T2DM who report high self-stigma may have lower social support, which can reduce their capacity for disease management. Additionally, larger social networks may be beneficial for individuals with T2DM in countries like Ghana, and interventions that expand network resources may facilitate diabetes control.


Dietary Supplement Use and Interactions with Tamoxifen and Aromatase Inhibitors in Breast Cancer Survivors Enrolled in Lifestyle Interventions.
The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.


Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous.
Xanthophyllomyces dendrorhous is a basidiomycete yeast that synthesizes carotenoids, mainly astaxanthin, which are of great commercial interest. Currently, there are many unknown aspects related to regulatory mechanisms on the synthesis of carotenoids in this yeast. Our recent studies showed that changes in sterol levels and composition resulted in upregulation of genes in the mevalonate pathway required for the synthesis of carotenoid precursors, leading to increased production of these pigments. Sterol Regulatory Element-Binding Proteins (SREBP), called Sre1 in yeast, are conserved transcriptional regulators of sterol homeostasis and other cellular processes. Given the results linking sterols and carotenoids, we investigated the role of SREBP in sterol and carotenoid synthesis in X. dendrorhous. In this study, we present the identification and functional characterization of the X. dendrorhous SRE1 gene, which encodes the transcription factor Sre1. The deduced protein has the characteristic features of SREBP/Sre1 and binds to consensus DNA sequences in vitro. RNA-seq analysis and chromatin-immunoprecipitation experiments showed that genes of the mevalonate pathway and ergosterol biosynthesis are directly regulated by Sre1. The sre1- mutation reduced sterol and carotenoid production in X. dendrorhous, and expression of the Sre1 N-terminal domain (Sre1N) increased carotenoid production more than twofold compared to wild-type. Overall, our results indicate that in X. dendrorhous transcriptional regulation of genes in the mevalonate pathway control production of the isoprenoid derivatives, carotenoids and sterol. Our results provide new insights into the conserved regulatory functions of SREBP/Sre1 and identify pointing to the SREBP pathway as a potential target to enhance carotenoid production in X. dendrorhous.


Pharmacodynamics and enantioselective pharmacokinetics of racemic carprofen in the horse.
Carprofen is a nonsteroidal anti-inflammatory drug of the 2-arylpropionate subclass. It contains a single chiral centre and exists in two enantiomeric forms. In this study rac-carprofen, at two dosages, 0.7 and 4.0 mg/kg, and placebo were administered i.v. to six New Forest horses in a three period cross-over study. The concentration-time profiles were established for R(-) and S(+)-carprofen for plasma and both inflamed (exudate) and noninflamed (transudate) tissue cage fluids. R(-)-carprofen was the predominant enantiomer in all three fluids, as indicated by plasma area under the curve (AUC) values for R(-) and S(+)-carprofen of 117.4 and 22.6 microg h/mL (low dose carprofen) and 557.5 and 138.1 microg h/mL (high dose carprofen) respectively. Penetration of both enantiomers into exudate was slow and limited and passage into transudate was even lower. The pharmacodynamics of rac-carprofen was investigated at both the molecular level and in terms of the ability to suppress components of the tissue cage inflammatory response. Low dose carprofen produced only moderate and transient inhibition of serum thromboxane (Tx)B2 but failed to affect exudate prostaglandin (PG)E2 concentrations, whilst suppression of exudate leukotriene (LT)B4 and beta-glucuronidase was not significant. High dose carprofen produced greater and more persistent inhibition of serum TxB2 and virtually abolished exudate PGE2 synthesis. Some inhibition of LTB4 and beta-glucuronidase in exudate was also obtained. At both dosages rac-carprofen reduced the swelling produced by intradermal bradykinin injection but only high dose carprofen was anti-inflammatory as indicated by suppression of temperature rise over exudate tissue cages and neither dose affected leucocyte numbers in exudate. When considered in conjunction with previous data on carprofen, the present findings indicate that carprofen is not a selective inhibitor of cyclooxygenase (COX) isoenzymes, COX-1 and COX-2 in the horse, although it may show some preference for COX-2 inhibition. Because low dose carprofen, which is the clinically recommended dosage, produces minimal inhibition of COX, it is likely to achieve its therapeutic effects at least partially through other pathways, possibly including weak to moderate inhibition of 5-lipoxygenase and of enzyme release. The good safety margin of carprofen in clinical use might also be explained by weak COX inhibition and by other actions at the molecular level.


Endoscopic dilation with bougies versus balloons in caustic esophageal strictures: 17-year experience from a tertiary care center.
Endoscopic dilation is the preferred management strategy for caustic esophageal strictures (CES). However, the differences in outcome for different dilators are not clear. We compared the outcome of CES using bougie and balloon dilators. Between January 2000 and December 2016, the following data of all the patients with CES were collected: demographic parameters, substance ingestion, number of strictures, number of dilations required to achieve ≥ 14 mm dilation, post-dilation recurrence, and total dilations. Patients were divided into two groups for the type of dilator, i.e., bougie or balloon. The two groups were compared for baseline parameter, technical success, short- and long-term clinical success, refractory strictures, recurrence rates, and major complications. Of the 189 patients (mean age 32.17 ± 12.12 years) studied, 119 (62.9%) were males. 122 (64.5%) patients underwent bougie dilation and 67 (35.5%) received balloon dilation. Technical success (90.1% vs. 68.7%, p < 0.001), short-term clinical success (65.6% vs. 46.3%, p value 0.01), and long-term clinical success (86.9% vs. 64.2%, p < 0.01) were higher for bougie dilators compared to balloon dilators. Twenty-four (12.7%) patients developed adverse events which were similar for two groups. On multivariate analysis, use of bougie dilators (aOR 4.868, 95% CI 1.027-23.079), short-term clinical success (aOR 5.785, 95% CI 1.203-27.825), and refractory strictures (aOR 0.151, 95% CI 0.033-0.690) were independent predictors of long-term clinical success. Use of bougie dilators is associated with better clinical success in patients with CES compared to balloon dilators with similar rates of adverse events.


Operational Effect of COVID-19 on Surgical Care at a Tertiary Pediatric Hospital.
The detrimental effects of the coronavirus disease 2019 (COVID-19) pandemic have profoundly disrupted surgical care at health care facilities worldwide. At our tertiary pediatric hospital, we made substantial adjustments to surgical suite utilization and staff member scheduling to account for reductions in surgical volume, increased demand for staff members in other sectors of the hospital, and the highly infectious properties of the virus. Perioperative leaders took advantage of the pandemic's disruption to clinical activities to design and implement a new procedure-scheduling process to rectify the inefficiencies that had accumulated as the previous system evolved. The implementation of said directives was largely facilitated by establishing communication with all involved parties for their input and feedback throughout the process. Although COVID-19 has had varying effects on procedural operations across pediatric health care facilities, we believe our institutional response to the disruptive forces of COVID-19 is of benefit to pediatric hospitals worldwide.


Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women.
Cholesterol and lipoprotein metabolism display pronounced gender differences. Premenopausal women have lower LDL and higher HDL cholesterol, whereas men display higher synthetic rates of bile acids and cholesterol. The effects of the administration of exogenous hormones to humans and animals indicate that these gender differences can often be explained by estrogens. We evaluated how increased levels of endogenous estrogens modulate cholesterol and lipoprotein metabolism in women. We studied healthy women during initiation of in vitro fertilization using blood samples obtained when endogenous estrogens were low and high. Cholesterol in VLDL and LDL, but not in HDL, was reduced 20% when estrogens were high. Apolipoprotein B levels decreased 13%. Apolipoprotein A-I and triglyceride levels increased 8% and 37%, respectively, whereas lipoprotein(a) levels were unchanged. Circulating PCSK9, a suppressor of LDL receptors, was reduced 14% when estrogens were high. Serum markers of bile acid and cholesterol synthesis were unaltered. Growth hormone levels increased 3-fold when estrogens were high, whereas insulin-like growth factor-1 and fibroblast growth factor-21 concentrations were unaltered. In women, Apolipoprotein B-containing particles and circulating PCSK9 are reduced when endogenous estrogens are high, indicating that endogenous estrogens induce hepatic LDL receptors partly through a posttranscriptional mechanism. However, estrogens do not stimulate bile acid or cholesterol synthesis.


Clinical evolution of prostatic intraepithelial neoplasia.
High-grade prostatic intraepithelial neoplasia (PIN) is most likely a precursor of prostate cancer and is frequently associated with it whereas the direct link between low-grade PIN and cancer is not established. The clinical evolution of isolated high-grade PIN has been the object of much concern because of the possibility of undiagnosed prostate cancer or the evolution of this premalignant lesion in invasive carcinoma. Parameters predictive of the later finding of prostate cancer on repeat biopsy in patients with PIN are of evident interest and we have reviewed our experience and recent data from the literature on this topic as well as on the clinical management of these patients. Low-grade PIN is not by itself a risk of later cancer found on repeat biopsy unless other factors such as PSA increase the cancer suspicion. Patients with low-grade PIN and high serum PSA should therefore undergo repeat biopsies. Patients with low-grade PIN and without additional factors should be followed. Patients with high-grade PIN should systematically be rebiopsied. If a second set is still consistent with PIN, they should undergo additional biopsies again within 3-6 months because they are likely to have an undiagnosed cancer.


Dense shearing flows of soft, frictional cylinders.
We perform discrete numerical simulations at a constant volume of dense, steady, homogeneous flows of true cylinders interacting via Hertzian contacts, with and without friction, in the absence of preferential alignment. We determine the critical values of the solid volume fraction and the average number of contacts per particle above which rate-independent components of the stresses develop, along with a sharp increase in the fluctuations of angular velocity. We show that kinetic theory, extended to account for a velocity correlation at solid volume fractions larger than 0.49, can quantitatively predict the measured fluctuations of translational velocity, at least for sufficiently rigid cylinders, for any value of the cylinder aspect ratio and friction investigated here. The measured pressure above and below the critical solid volume fraction is in agreement with a recent theory originally intended for spheres that conjugates extended kinetic theory, the finite duration of collisions between soft particles and the development of an elastic network of long-lasting contacts responsible for the rate-independency of the flows in the supercritical regime. Finally, we find that, for sufficiently rigid cylinders, the ratio of shear stress to pressure in the subcritical regime is a linear function of the ratio of the shear rate to a suitable measure of the fluctuations of translational velocity, in qualitative accordance with kinetic theory, with an intercept that increases with friction. A decrease in the particle stiffness gives rise to nonlinear effects that greatly diminishes the stress ratio.


Area under Immunosurveillance: Dedicated Roles of Memory CD8 T-Cell Subsets.
Immunological memory, defined as the ability to respond in an enhanced manner upon secondary encounter with the same pathogen, can provide substantial protection against infectious disease. The improved protection is mediated in part by different populations of memory CD8 T cells that are retained after primary infection. Memory cells persist in the absence of pathogen-derived antigens and enable secondary CD8 T-cell responses with accelerated kinetics and of larger magnitude after reencounter with the same pathogen. At least three subsets of memory T cells have been defined that are referred to as central memory CD8 T cells (Tcm), effector memory CD8 T cells (Tem), and tissue-resident memory CD8 T cells (Trm). Tcm and Tem are circulating memory T cells that mediate bodywide immune surveillance in search of invading pathogens. In contrast, Trm permanently reside in peripheral barrier tissues, where they form a stationary defensive line of sentinels that alert the immune system upon pathogen reencounter. The characterization of these different subsets has been instrumental in our understanding of the strategies that memory T cells employ to counter invading pathogens. It is clear that memory T cells not only have a numerical advantage over naive T cells resulting in improved protection in secondary responses, but also acquire distinct sets of competencies that assist in pathogen clearance. Nevertheless, inherent challenges are associated with the allocation of memory T cells to a limited number of subsets. The classification of memory T cells into Tcm, Tem, and Trm may not take into account the full extent of the heterogeneity that is observed in the memory population. Therefore, in this review, we will revisit the current classification of memory subsets, elaborate on functional and migratory properties attributed to Tcm, Tem, and Trm, and discuss how potential heterogeneity within these populations arises and persists.


[Basic study of bone mineral density in os calcis by single energy X-ray absorptiometry].
We studied bone mineral density (BMD) in the os calcis by means of single energy X-ray absorptiometry (SXA), and BMD in the third lumbar spine by means of dual energy X-ray absorptiometry (DXA), results were as follows. (1) The doses absorbed in SXA at the exposure site and the opposite site were measured by thermoluminescent dosimetry. The dose absorbed in SXA may be lower than that in DXA. (2) The BMD of the os calcis was measured in 30 female volunteers by SXA and that of the third lumbar spine by DXA, and age, weight, height, and consequences of physical exertion were investigated. BMD as determined by SXA was significantly correlated with that determined by DXA (r = 0.65). BMD as determined by SXA and DXA tended to decrease with age, to increase with height and weight, and to be significantly higher in those who made some physical exertion. In conclusion, SXA may be a useful method for the measurement of BMD.


Comparing homeless smokers to economically disadvantaged domiciled smokers.
We compared characteristics of homeless smokers and economically disadvantaged domiciled smokers (Dallas, TX; August 2011-November 2012). Although findings indicated similar smoking characteristics across samples, homeless smokers (n = 57) were exposed to more smokers and reported lower motivation to quit, lower self-efficacy for quitting, more days with mental health problems, and greater exposure to numerous stressors than domiciled smokers (n = 110). The sample groups reported similar scores on measures of affect, perceived stress, and interpersonal resources. Results may inform novel cessation interventions for homeless smokers.


Do dietary interventions improve health outcomes in people with multiple sclerosis? A cochrane review summary with commentary.
A broad range of complementary and alternative medicine (CAM) approaches, including different dietary interventions, alone or in conjunction with conventional medicine are currently trailed in people with multiple sclerosis (MS). Published clinical and experimental data suggest that certain dietary interventions may improve MS-related health outcomes. To assess the effectiveness of dietary interventions to improve MS-related health outcomes. To summarize the updated Cochrane Review "Dietary interventions for multiple sclerosis-related outcomes" conducted by Parks et al. Best available evidence was discussed from the rehabilitation perspective. Overall 30 RCTs (with 2335 participants) evaluated a range of dietary interventions: polyunsaturated fatty acids, antioxidant supplements, dietary programmes and other dietary supplements. All included trials had one or more methodological issues leading to an unknown or high risk of bias. The findings suggest that the evidence is uncertain about the effect of dietary interventions on MS-related health outcomes. The evidence for dietary interventions in people with MS is sparse and uncertain, and more robust studies are needed.


The use of gonad shielding in paediatric hip and pelvis radiographs.
The problem of inaccurate placement of gonad shields in children has been highlighted by several publications nationally and internationally over the past decade and more. Here, we review the literature and present the results of a regional audit designed to assess the use and accuracy of placement of gonad shields for hip and pelvis radiographs in children. 100 consecutive anteroposterior hip or pelvis radiographs in patients under the age of 16 years were reviewed in each of 9 centres. We also included the most recent and all previously available relevant radiographs. A total of 2405 radiographs were reviewed with regard to the presence of a shield and to the accuracy of any shield placement with respect to gonad protection and visualization of orthopaedic landmarks. It is recommended that gonad shields are used in all follow-up paediatric pelvis radiographs. Our results show they were only used in 70% of such cases. When placed, only 38% of all shields were considered to be positioned accurately. For cases where shielding was indicated, an accurately placed shield was present in just 26% of radiographs. Formal written departmental guidelines for shield use were only available in two centres. We conclude that clear guidelines need to be formulated which, together with shield redesign, improved training and audit, should increase effective gonad protection for children.


Anxiety and Depression Among College Students During the COVID-19 Lockdown: A Cross-Sectional Survey in Jiangsu, China.
This study aimed to explore the levels of anxiety and depression in a sample of home-quarantined college students to identify the risk factors for psychological distress during the COVID-19 lockdown. A total of 1156 college students studying in Jiangsu, China, participated from August 5 to August 14. A structured questionnaire was used to collect data anonymously, including demographic characteristics, the generalized anxiety disorder-7 (GAD-7) questionnaire, the patient health questionnaire-9 (PHQ-9), a physical activity scale, and items related to COVID-19. The chi-square test and Fisher's exact test were employed to establish the differences in levels of anxiety and depression across sociodemographic characteristics. Binary logistic regression was applied to measure the predictors of levels of anxiety and depression, and associations were considered significant at p <0.05. The estimates of anxiety and depression were 48.1% and 57.6%, respectively. The univariate analysis indicated a significant difference in anxiety levels across student grades, whether the student was an only child, the distance from the worst-hit areas, and physical activity/exercise intensity. Physical activity intensity and living in communities with infected people were statistically correlated with the level of depression. Binary logistic regression results indicated that the predictive factors for anxiety were living within a short distance from the worst-hit areas (10~20 km), engaging in higher education (graduate students), and low-intensity daily exercise. Factors statistically predicting depression symptoms were having siblings, a COVID-19 diagnosis in the community and low-intensity daily exercise. During outbreaks, students in an extremely stressful state are more likely to develop anxiety and depression, particularly postgraduates. Psychological interventions to reduce fears and encourage exercise should be available to home-quarantined college students. Students who live in the worst-hit areas and are not the only child in the family should be prioritized.


Interpretation and actionability of genetic variants in cardiomyopathies: a position statement from the European Society of Cardiology Council on cardiovascular genomics.
This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family. A partnership between clinicians and patients helps to solve major uncertainties and provides reliable and clinically actionable information.


Comprehensive Analysis of CRIP1 in Patients with Ovarian Cancer, including ceRNA Network, Immune-Infiltration Pattern, and Clinical Benefit.
With the development of sequencing technology, an increasing number of biomarkers have been identified in ovarian cancer (OC). However, there have been few comprehensive analyses of CRIP1 in patients with OC. Logistic regression analysis was conducted to analyze the correlations between clinical characteristics and CRIP1 expression. Kaplan-Meier survival analysis was used to explore the difference in survival in each clinical subgroup. In addition, univariate and multivariate Cox regression analyses were further used to confirm the independent prognostic values of CRIP1. We further constructed ceRNA network based on the difference analysis. Subsequently, we used the ssGSEA algorithm to excavate the correlation between CRIP1 and tumor-infiltrating immune cells. Moreover, the potential biological functions of CRIP1 were investigated by gene function annotation. Finally, we knocked down CRIP1 gene for preliminary biological function verification in A2780 and SKOV-3 cell lines. The overexpression of CRIP1 was confirmed in The Cancer Genome Atlas (TCGA) cohort, immunohistochemistry, and OC cell lines. CRIP1 overexpression was correlated with the FIGO stage according to a logistic regression analysis that used the median of CRIP1 expression as a categorization of the dependent variable. Survival analysis revealed that CRIP1 was associated with a poor prognosis in most clinical subgroups and acts as an independent prognostic marker in OC patients. In immuno-bioinformatics analysis, CRIP1 is associated to majority of immune cells. This is noteworthy given that we identified that the ceRNA network based on CRIP1 may regulate progression in OC. In addition, gene enrichment analysis suggested CRIP1 may be involved in the JAK-STAT signaling pathway, etc. Finally, we found that knockdown CRIP1 could inhibit the proliferation of OC cells. We provided robust evidences that CRIP1 is an indicator of poor prognosis and a potential target for immunotherapy in patients with OC.


Ciprofloxacin suppresses Cyp3a in mouse liver by reducing lithocholic acid-producing intestinal flora.
Ciprofloxacin (CPX), a new quinolone antibiotic, is reported to reduce CYP3A expression in the liver when administered to rats. The present study investigates whether the reduction in intestinal flora is involved in this reduction of CYP3A. While hepatic Cyp3a11 expression and triazolam metabolic activity were significantly reduced by CPX treatment of SPF mice, no significant changes were seen by CPX treatment of germ-free (GF) mice. Lithocholic acid (LCA)-producing bacteria in the feces as well as hepatic level of taurine conjugate of LCA were significantly reduced in CPX-treated SPF mice. Cyp3a11 expression in GF mice was significantly elevated when treated with LCA, known as an activator of fernesoid X receptor and pregnane X receptor. These results indicate that antibiotics such as CPX, having antimicrobial spectrums against LCA-producing bacteria, possibly cause decrease in LCA in the liver, resulting in lower CYP3A expression. The intestinal flora is reported to be altered also by stress, disease and age etc. The findings of the present study suggest that these changes in intestinal flora may modify CYP expression and contribute to individual differences in pharmacokinetics.


Metoclopramide-induced raised intracranial pressure after head injury.
We report a case of raised intracranial pressure in a head-injured patient following the intravenous administration of metoclopramide. The patient required admission to an intensive care unit after a road traffic accident. A CT scan of the head was consistent with diffuse axonal injury and supportive management included intracranial pressure monitoring. On the third day after admission, intravenous metoclopramide 10mg was administered to aid gastric emptying during nasogastric feeding. Intracranial pressure increased to 39mmHg from a baseline of 15-20mmHg. The same dose of metoclopramide was repeated the next day during transcranial doppler studies with an increase in ICP to 34mmHg and an associated rise in middle cerebral artery systolic blood velocity from 122cms-1 to 150cms-1. This effect of metoclopramide has not been previously reported.


Transcriptional and DNA Methylation Signatures of Subcutaneous Adipose Tissue and Adipose-Derived Stem Cells in PCOS Women.
Polycystic ovary syndrome (PCOS) is often associated with metabolic syndrome features, including central obesity, suggesting that adipose tissue (AT) is a key organ in PCOS pathobiology. In this study, we compared both abdominal (ABD) and gluteofemoral (GF) subcutaneous AT in women with and without PCOS. ABD and GF subcutaneous ATs from PCOS and BMI/WHR-matched control women were analyzed by RT-qPCR, FACS and histology. ABD and GF adipose-derived stem cell (ASC) transcriptome and methylome were analyzed by RNA-seq and DNA methylation array. Similar to the control group with abdominal obesity, the GF AT of PCOS women showed lower expression of genes involved in lipid accumulation and angiogenesis compared to ABD depot. FACS analysis revealed an increase in preadipocytes number in both AT depots from PCOS. Further pathway analysis of RNA-seq comparisons demonstrated that the ASCs derived from PCOS are pro-inflammatory and exhibit a hypoxic signature in the ABD depot and have lower expression of adipogenic genes in GF depot. We also found a higher CpG methylation level in PCOS compared to control exclusively in GF-ASCs. Our data suggest that ASCs play an important role in the etiology of PCOS, potentially by limiting expansion of the healthy lower-body AT.


Serial abdominal closure with Gore-tex mesh and Rives-Stoppa for an open abdomen secondary to intra-abdominal hypertension in burns.
Intra-abdominal hypertension (IAH) leading to abdominal compartment syndrome (ACS) commonly occurs in major burns. To relieve the excess pressure, decompressive laparotomy is done which can lead to an open abdomen. Closure of the abdomen after a decompressive laparotomy is very difficult with bowel oedema. We describe our technique of closing the open abdomen in such situations with a combination of serial abdominal wall closure with a layered mesh and the Rives-Stoppa component separation technique.


Laminarin from Irish Brown Seaweeds Ascophyllum nodosum and Laminaria hyperborea: Ultrasound Assisted Extraction, Characterization and Bioactivity.
Ultrasound assisted extraction (UAE), purification, characterization and antioxidant activity of laminarin from Irish brown seaweeds Ascophyllum nodosum and Laminarina hyperborea were investigated. UAE was carried out using 60% ultrasonic power amplitude and 0.1 M hydrochloric acid for 15 min. Separately, solid-liquid extraction was carried in an orbital shaker using 0.1 M hydrochloric acid at 70 °C for 2.5 h. UAE with hydrochloric acid resulted in the highest concentration of laminarin, 5.82% and 6.24% on dry weight basis from A. nodosum and L. hyperborea, respectively. Purification of all extracts was carried out using molecular weight cut off dialysis at 10 kDa. Characterization of the laminarin fraction was carried out using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Antioxidant activity of A. nodosum and L. hyperborea extracts had 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition levels of 93.23% and 87.57%, respectively. Moreover, these extracts have shown inihibition of bacterial growth of Staphylcoccus aureus, Listeria monocytogenes, Escherichia coli and Salmonella typhimurium.


Pressure ulcer prevalence and prevention rates in Abu Dhabi: an update.
This article compares the results from a recent pressure ulcer (PU) prevalence audit at the Sheikh Khalifa Medical City (SKMC) hospital in Abu Dhabi to identify the impact of new prevention initiatives introduced around 2013 and establish the effectiveness of PU prevention strategies, judged quality of nursing care, and costs associated with patients developing a hospital-acquired pressure ulcer (HAPU). The methods used were based on a previous point prevalence study involving 441 acute care patients, who were assessed using the International Pressure Ulcer Prevalence (IPUP) Survey. Following pre-selection of a 24-hour period for data capture, hospital staff collected PU data. Hill-Rom provided SKMC with an electronic report comprising various epidemiological and financial outputs. PU prevalence was 10.4% in 2018 versus 6.4% in 2013. The 2018 HAPU prevalence was 1.8% versus 2% in 2013. The 2018 findings were in line with IPUP's international benchmarks. In 2018, 99% of patients had their skin assessed and PU risk documented within 24 hours of admission, leading to rapid implementation of a prevention care plan. Most patients who developed a HAPU (n=8) were female (62%) and aged 20-29 years old (25%) or 70-79 years old (25%). All HAPU patients lay on three layers of linen, most on their side (88%) and 75% were hospitalised for >30 days. Costs were estimated for the eight HAPU patients; weighted average cost (per case) was around US$8035.32, giving a total estimated cost of US$64,282.54. Total annual cost (average length of stay basis) for the eight patients was estimated at US$1,830,082.32. The PU prevention plan at SKMC proved to be effective, reflected by a low HAPU prevalence rate, suggesting an excellent quality of patient care.


Dimeric supramolecular motifs of two carboxylate-guanidinium compounds.
The structures of N-benzyl-N'-{6-[(4-carboxylatobenzyl)aminocarbonyl]-2-pyridylmethyl}guanidinium, C(23)H(23)N(5)O(3), (I), and N-[2-(benzylaminocarbonyl)ethyl]-N'-{6-[(4-carboxylatobenzyl)aminocarbonyl]-2-pyridylmethyl}guanidinium monohydrate, C(26)H(28)N(6)O(4).H(2)O, (II), both form three-dimensional supramolecular hydrogen-bonded networks based on a dimeric primary synthon involving carboxylate-guanidinium linkages. The differences in the geometries and hydrogen-bonding connectivities are driven by the additional methylpropionamide group and water of crystallization of (II).


Acinetobacter baumannii in human body louse.
While we were isolating Bartonella quintana from body lice, 40 Acinetobacter baumannii strains were also isolated and genotyped. One clone was unique and the other was ampicillin susceptible. A. baumannii DNA was later detected in 21% of 622 lice collected worldwide. These findings show an A. baumannii epidemic in human body lice.


Cognitive rehabilitation for executive dysfunction in adults with stroke or other adult non-progressive acquired brain damage.
Executive functions are the controlling mechanisms of the brain and include the processes of planning, initiation, organisation, inhibition, problem solving, self monitoring and error correction. They are essential for goal-oriented behaviour and responding to new and novel situations. A high number of people with acquired brain injury, including around 75% of stroke survivors, will experience executive dysfunction. Executive dysfunction reduces capacity to regain independence in activities of daily living (ADL), particularly when alternative movement strategies are necessary to compensate for limb weakness. Improving executive function may lead to increased independence with ADL. There are various cognitive rehabilitation strategies for training executive function used within clinical practice and it is necessary to determine the effectiveness of these interventions. To determine the effects of cognitive rehabilitation on executive dysfunction for adults with stroke or other non-progressive acquired brain injuries. We searched the Cochrane Stroke Group Trials Register (August 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library, August 2012), MEDLINE (1950 to August 2012), EMBASE (1980 to August 2012), CINAHL (1982 to August 2012), PsycINFO (1806 to August 2012), AMED (1985 to August 2012) and 11 additional databases. We also searched reference lists and trials registers, handsearched journals and conference proceedings, and contacted experts. We included randomised trials in adults after non-progressive acquired brain injury, where the intervention was specifically targeted at improving cognition including separable executive function data (restorative interventions), where the intervention was aimed at training participants in methods to compensate for lost executive function (compensative interventions) or where the intervention involved the training in the use of an adaptive technique for improving independence with ADL (adaptive interventions). The primary outcome was global executive function and the secondary outcomes were specific components of executive function, working memory, ADL, extended ADL, quality of life and participation in vocational activities. We included studies in which the comparison intervention was no treatment, a placebo intervention (i.e. a rehabilitation intervention that should not impact on executive function), standard care or another cognitive rehabilitation intervention. Two review authors independently screened abstracts, extracted data and appraised trials. We undertook an assessment of methodological quality for allocation concealment, blinding of outcome assessors, method of dealing with missing data and other potential sources of bias. Nineteen studies (907 participants) met the inclusion criteria for this review. We included 13 studies (770 participants) in meta-analyses (417 traumatic brain injury, 304 stroke, 49 other acquired brain injury) reducing to 660 participants once non-included intervention groups were removed from three and four group studies. We were unable to obtain data from the remaining six studies. Three studies (134 participants) compared cognitive rehabilitation with sensorimotor therapy. None reported our primary outcome; data from one study was available relating to secondary outcomes including concept formation and ADL. Six studies (333 participants) compared cognitive rehabilitation with no treatment or placebo. None reported our primary outcome; data from four studies demonstrated no statistically significant effect of cognitive rehabilitation on secondary outcomes. Ten studies (448 participants) compared two different cognitive rehabilitation approaches. Two studies (82 participants) reported the primary outcome; no statistically significant effect was found. Data from eight studies demonstrated no statistically significant effect on the secondary outcomes. We explored the effect of restorative interventions (10 studies, 468 participants) and compensative interventions (four studies, 128 participants) and found no statistically significant effect compared with other interventions. We identified insufficient high-quality evidence to reach any generalised conclusions about the effect of cognitive rehabilitation on executive function, or other secondary outcome measures. Further high-quality research comparing cognitive rehabilitation with no intervention, placebo or sensorimotor interventions is recommended.


Structural MR image processing using the BRAINS2 toolbox.
Medical imaging has opened a new door into biomedical research. In order to study various diseases of the brain and detect their impact on brain structure, robust and user friendly image processing packages are required. These packages must be multi-faceted to distinguish variations in size, shape, volume, and the ability to detect longitudinal changes over the course of an illness. This paper describes the BRAINS2 image processing package, which contains both manual and automated tools for structural identification, methods for tissue classification and cortical surface generation. These features are described in detail, as well as the reliability of these procedures.


Vasopressin during cardiopulmonary resuscitation: a progress report.
In patients undergoing cardiopulmonary resuscitation, circulating endogenous vasopressin concentrations were significantly higher in successfully resuscitated patients than in patients who died. These observations have prompted several investigations to assess the role of vasopressin to improve cardiopulmonary resuscitation management. Literature review. In the cardiopulmonary resuscitation laboratory, vasopressin improved vital organ blood flow, cerebral oxygen delivery, the probability of restoring spontaneous circulation, and neurologic recovery better than epinephrine. In pediatric preparations with asphyxia, epinephrine was superior to vasopressin, whereas in both pediatric pigs with ventricular fibrillation and adult porcine models with asphyxia, combinations of vasopressin and epinephrine proved to be highly effective. In addition, vasopressin enabled short- and long-term survival in a porcine model of uncontrolled hemorrhagic shock. In a recently published European, multiple-center trial, 1,219 adult patients with out-of-hospital cardiac arrest were randomized to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine followed by additional epinephrine if needed. The clinical study did not confirm laboratory data showing vasopressin to be more effective than epinephrine in ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine was more effective than epinephrine alone in the treatment of refractory cardiac arrest. According to new data from the European vasopressin study, we suggest, first, the administration of 1 mg of epinephrine, followed alternately by 40 IU of vasopressin and 1 mg of epinephrine every 3 mins in adult cardiac arrest victims, regardless of the initial electrocardiographic rhythm.


Oxygen Monitoring Reduces the Risk for Retinopathy of Prematurity in a Mexican Population.
Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High levels of oxygen saturation are a well-known risk factor for ROP. To assess the frequency of ROP type 1 needing treatment after improved oxygen monitoring (2011) in a Mexican preterm population selected for WINROP analyses and to retrospectively revalidate WINROP, an online surveillance system identifying infants at risk of developing ROP type 1. Preterm infants born with birth weight (BW) <1,750 g and/or at gestational age (GA) ≤34 weeks, screened for ROP in 2012-2014 at the Hospital Civil de Guadalajara, Mexico were included (n = 151). Eighty-five infants with GA <32 weeks qualified for WINROP analyses. GA, BW, maximal ROP stage, ROP treatment and weekly weights were recorded. The results in the present study were compared to those of a previous WINROP study in the same hospital (2005-2010; n = 352). In the present WINROP cohort, 11.8% of the infants born at GA <32 weeks received treatment compared to 51.0% of the infants in the previous WINROP cohort. One infant (3%) born at GA ≥32 weeks received treatment during the present study period compared to 35.6% during the previous period. WINROP displayed 80.0% sensitivity in infants born at GA <32 weeks in the present study compared to 84.7% in the previous study. Uncontrolled oxygen supplementation is the major risk factor for severe ROP in infants born at GA ≥32 weeks. After improved oxygen monitoring, the frequency of ROP treatment was dramatically reduced at the Hospital Civil de Guadalajara, Mexico.


Oxidized oligogalacturonides activate the oxidation of indoleacetic Acid by peroxidase.
Partial hydrolysis of polygalacturonic acid with a purified alpha-1,4-endopolygalacturonase yielded oligogalacturonides and trace amounts of a series of modified oligogalacturonides. Three of the minor products were isolated and identified as oxidized oligogalacturonides possessing termini of galactaric acid. Oxidation of indole-3-acetic acid by peroxidases was activated by oxidized oligogalacturonides but not by normal analogs.


Selective IgA deficiency and anaphylactoid transfusion reaction: a case report.
Anaphylactoid transfusion reaction following the administration of incompatible blood products can be life threatening, but accounts for only a very small proportion of all transfusion reactions. One of the causes of anaphylactoid transfusion reaction is the reaction of patient's anti-immunoglobulin A(IgA) with plasma IgA which is usually present in transfused blood. We report a case who had anaphylactoid transfusion reactions after transfusion of only a few milliliters of packed RBC from 3 consecutive donors, in spite of compatible pretransfusion crossmatches. The patient's serum revealed IgA deficiency accompanied by high-titer anti-IgA. The family study showed that one of her sons had partial IgA deficiency accompanied by anti-IgA2. In conclusion, although selective IgA deficiency is rare in Taiwan, it may still occasionally result in severe anaphylactoid transfusion reactions.


Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction.
Descending vasa recta (DVR) are 12- to 15-μm microvessels that supply the renal medulla with blood flow. We examined the ability of intrinsic nitric oxide (NO) and reactive oxygen species (ROS) generation to regulate their vasoactivity. Nitric oxide synthase (NOS) inhibition with N(ω)-nitro-l-arginine methyl ester (l-NAME; 100 μmol/l), or asymmetric N(G),N(G)-dimethyl-l-arginine (ADMA; 100 μmol/l), constricted isolated microperfused DVR by 48.82 ± 4.34 and 27.91 ± 2.91%, respectively. Restoring NO with sodium nitroprusside (SNP; 1 mmol/l) or application of 8-Br-cGMP (100 μmol/l) reversed DVR vasoconstriction by l-NAME. The superoxide dismutase mimetic Tempol (1 mmol/l) and the NAD(P)H inhibitor apocynin (100, 1,000 μmol/l) also blunted ADMA- or l-NAME-induced vasoconstriction, implicating a role for concomitant generation of ROS. A role for ROS generation was also supported by an l-NAME-associated rise in oxidation of dihydroethidium that was prevented by Tempol or apocynin. To test whether H(2)O(2) might play a role, we examined its direct effects. From 1 to 100 μmol/l, H(2)O(2) contracted DVR whereas at 1 mmol/l it was vasodilatory. The H(2)O(2) scavenger polyethylene glycol-catalase reversed H(2)O(2) (10 μmol/l)-induced vasoconstriction; however, it did not affect l-NAME-induced contraction. Finally, the previously known rise in DVR permeability to (22)Na and [(3)H]raffinose that occurs with luminal perfusion was not prevented by NOS blockade. We conclude that intrinsic production of NO and ROS can modulate DVR vasoactivity and that l-NAME-induced vasoconstriction occurs, in part, by modulating superoxide concentration and not through H(2)O(2) generation. Intrinsic NO production does not affect DVR permeability to hydrophilic solutes.


[Intraocular correction of aphakia after cataract extraction for uveitis in adolescents].
To demonstrate 3 cases with pediatric pseudophakia after cataract extraction as a complication of unilateral uveitis. The boys were at the age of 8, 11 and 15 years at the moment of surgery. Uveitis was monocular, the etiology unknown and clinically significant cataract was diagnosed after several months from the beginning of inflammation. The last recurrence of uveitis was observed 1 to 6 months before operation. There were intermediate uveitis (2 cases) and anterior uveitis (1 cases). In 2 eyes PMMA implant was placed in-the-bag and in one eye in the ciliary sulcus. During surgery we did not observe any complications except greater tendency to bleeding. Follow-up after operation ranged from 1.5 to 2.5 years. Visual acuity before cataract extraction was 0.01; 0.04 and 0.02 and during last visit after surgery it was 0.9, 0.6 and 0.4 respectively. Postoperative near distance visual acuity was 0.5, 0.75 and 1.25. We observed cystoid macular oedema in the latter case. Two months after PC-IOL implantation the symptoms of mild inflammation in the eye of 15-year-old boy with anterior uveitis occurred. Intraocular pressure before and after operation ranged from 12 to 17 mm Hg. Corneal central endothelial cell density was from 2850/mm2 to 3100/mm2 before and from 2469/mm2 to 2979/mm2 during last visit. Cases of posterior pseudophakia during uveitis in children showing good functional and anatomical state of eyes in the long term observation after IOL implantation recommend the intraocular correction in carefully selected uveitic pediatric patients.


[Labor supply and economic fluctuations: Brazil, 1979-1986].
"The purpose of this article is to study how the Brazilian labor supply responded to the business cycle of the period 1979-1986. In doing so, the article analyzes the growth and the structure of the Brazilian labor force as well as its demographic traits over that time span. The analysis focuses on the cyclical sensitivity of the labor force participation rate (LFPR) of particular labor force groups. The study breaks down the LFPR by age, sex, schooling and family income. The main finding is that the labor supply measured by the time series behavior of the LFPR is sensitive to the business cycle although the direction and the degree of responsiveness varies among labor force groups." (SUMMARY IN ENG)


Limited proteolysis of (1,3)-beta-glucan (callose) synthase from Beta vulgaris L: topology of protease-sensitive sites and polypeptide identification using Pronase E.
Plasma membrane (PM) vesicles of defined sidedness were obtained from Beta vulgaris L. and subjected to limited proteolysis to investigate the topology and subunit composition of UDP-glucose: (1,3)-beta-glucan (callose) synthase (CalS). Latency experiments demonstrated that protease-sensitive sites on the CalS complex are located primarily at the cytoplasmic face of the PM, with little or no CalS inactivation occurring as the result of proteolysis at the apoplastic face. In the PM-bound form, CalS activity was resistant to inactivation by Pronase E, however at least four polypeptides previously implicated as possible CalS components (92, 83, 57 and 43 kDa) were extensively hydrolyzed. Polypeptides of 31, 29 and 27 kDa resisted Pronase E hydrolysis and were also enriched in CalS fractions purified by glycerol gradient centrifugation and product entrapment. In contrast to PM-bound CalS, purified CalS was rapidly hydrolyzed by Pronase E, indicating that most Pronase E-sensitive sites are deeply embedded within the PM. This study provides direct biochemical evidence that hydrophobic integral membrane proteins oriented primarily towards the cytoplasmic face of the PM are important for callose biosynthesis in Beta. Furthermore, these results form the basis of a biochemically derived working model largely consistent with morphologically derived models proposed for intramembrane PM-bound, microfibril-synthesizing complexes in higher plants.


Engraftment of hematopoietic stem cells in nonmyeloablated and myeloablated hosts.
Hematopoietic stem cell engraftment has traditionally been assessed in irradiated murine hosts. More recently, we and others have shown that engraftment is virtually quantitative in host animals who have received no preconditioning myeloablation. It appears that at the stem cell level, engraftment may even be favored in the normal host. The final phenotypic readout in the engrafted animal is then determined by competition between the engrafted stem cells and the number of residual host stem cells. Further studies have indicated that with cytokine exposure in vitro, in vivo or 5-fluorouracil exposure and consequent stimulation of primitive hematopoietic stem cells to enter cell cycle, an engraftment defect relating to long-term engraftment occurs. This occurs in the face of an expansion of cycling surrogate stem cells as mirrored by the high proliferative potential colony-forming cell. These data indicate that the phenotype of the hematopoietic stem cell, as assessed in vitro, may not give insight into the phenotype of these cells in vivo.


[The principle of nasal defects repair based on the frontal and temporal vessels anatomy].
After dissection of 9 corpes' (18 sides) vessels of the forehead, nose and temporal, we have discovered that the superatrochlear arteries run upward bilaterally, the branches of the supertrochelear arteries, the superficial branches of the supraorbital arteries and the front branches of the superficial temporal form a network--the frontal artery anastomotic net. The main trank and the parital branches of the superficial temporal arteries give off 2-3 ear branches. Based on these findings, we have made a series of explor atire researches, designed several new kinds of skin flaps for repairing the nasal defects, and improved a number traditional skin flaps. Guided by the above mentioned principles, we have successfully reconstructed 32 different kinds of nasal defects and achieved good results.


[Effects of Lin28a and Lin28b on let-7 family activity].
In this report, we study the effects of over-expression of Lin28a and Lin28b on let-7 family activity in HeLaS3. Firstly, we constructed pAAV2neo-Lin28a and pAAV2neo-Lin28b to express Lin28a and Lin28b, respectively. Then, pAAV2neo-Lin28a and pAAV2neo-Lin28b were transfected into HeLaS3, selected with G418 and obtained cell lines, HeLaS3/pAAV2neo-Lin28a and HeLaS3/pAAV2neo-Lin28b, to express Lin28a and Lin28b stably. Thereafter, we constructed eight plasmid vectors for detection of let-7 family activity based on pAAV2neo-Gluc-(Fluc). These vectors were further packaged into recombinant adeno-associated viral vectors (rAAV) which were used as sensors, nominated as Asensors, to detect inhibition activity of miRNA at post-transcriptional level. Subsequently, with HeLaS3 as a control, we assayed expression levels of Lin28a and Lin28b by Western blot, detected expression levels of let-7 family by QRT-PCR, and tested let-7 family activity by Asensors in HeLaS3/pAAV2neo-Lin28a and HeLaS3/pAAV2neo-Lin28b. Results demonstrated that both HeLaS3/pAAV2neo-Lin28a and HeLaS3/pAAV2neo-Lin28b could express Lin28a and Lin28b effectively. Compared with HeLaS3, the expression level of let-7 family except let-7e declined in HeLaS3/pAAV2neo-Lin28a. But declining extent among members of let-7 family was different. The let-7 family activity also decreased while the decreasing extent varied among members. Furthermore, the activity level was not consistent with its expression level for the same member in let-7 family. Compared with HeLaS3, both expression level and activity level of let-7 family in HeLaS3/ pAAV2neo-Lin28b were decreased. However, the decreasing extent of let-7 family expression changes was larger than that of HeLaS3/pAAV2neo-Lin28a while the decreasing extent of activity changes was similar. In this study, we established a method to detect and compare post-transcriptional inhibition level mediated by miRNA complementary targets. We firstly clarified the effect of Lin28a and Lin28b on let-7 family activity profile and found that this effect was not the same as that at expression level of let-7 family, suggesting that it was more comprehensive to understand miRNA regulation roles to detect both miRNA expression and activity. This paves a way for further research on mechanism of regulation of let-7 family.


Daily Readiness Huddles in Radiology-Improving Communication, Coordination, and Problem-Solving Reliability.
Deploying an intentional daily management process is a key part to create high-reliability culture. Key components described in the literature for a successfully daily management process include leadership standard work, visual controls, daily accountability processes, and the discipline to stick to the process over the long term. We believe that the institution of a daily readiness huddle has helped us better coordinate and communicate as a department and improved our ability to deliver imaging services on a daily basis. The daily readiness huddle has enabled us to more rapidly identify issues and has brought accountability to seeing solutions to those issues brought to fruition. In addition, it has helped with team building, including between the radiologists and the nonphysician staff.


Destinations matter: The association between where older adults live and their travel behavior.
The positive effect of physical activity in the prevention and treatment of many chronic diseases and age-related disabilities, such as mobility-disability, are widely accepted. Mobility is broadly defined as the ability of individuals to move themselves within community environments. These two concepts -physical activity and mobility - are closely linked and together contribute to older adults living healthy, independent lives. Neighborhood destinations may encourage mobility, as older adults typically leave their homes to travel to specific destinations. Thus, neighborhoods with a high prevalence of destinations may provide older adults an attractive opportunity to walk, instead of drive, and thereby obtain incidental physical activity. We know surprisingly little about the specific types of destinations older adults deem relevant and even less about destinations that support the mobility of older adults with low income. Accessible neighborhood destinations may be especially important to older adults with low income as they are more likely to walk as a primary travel mode. Conversely, this population may also be at increased risk of functional impairments that negatively affect their ability to walk. As a means to fill this information gap we aimed to better understand the mobility habits of older adults with low income. Thus, our specific objectives were to: (1) describe the types of destinations older adults with low income most commonly travel to in one week; and (2) determine the association between the prevalence of neighborhood destinations and the number of transportation walking trips these individuals make (average per day). We conducted a cross-sectional study of community-dwelling older adults with low income residing within Metro Vancouver, Canada. We assessed participant travel behavior (frequency, purpose, mode, destination) using seven-day travel diaries and measured the prevalence of neighborhood destinations using the Street Smart Walk Score. We also assessed participants' sociodemographic characteristics and mobility (physical function, car access, confidence walking). We used a negative binomial model to determine the association between Street Smart Walk Score and number of transportation walking trips (average per day). Our sample was comprised of 150 participants (median age 74 years; 51 men) from who we acquired at least one day of travel diary data (range = 1-7 days). Participants made three trips per day (2, 5; median P25, P75) and travelled to six different destination types per week (5, 9; median P25, P75). Destinations most relevant to older adults were grocery stores, malls, and restaurants/cafés. Each 10-point increase in Street Smart Walk Score was associated with a 20% increase in the number of transportation walking trips (average per day, incidence rate ratio = 1.20, 95% CI = 1.12, 1.29). Our findings provide preliminary evidence regarding destinations that may be most relevant to older adults. They also suggest that the prevalence of these neighborhood destinations may encourage walking. As we approach a new era of healthy city benchmarks, our findings guide policy makers and developers to retrofit and develop communities that support the mobility, health, and independence of older adults.


Towards more comprehensive health law and policy research.
In this comment, and drawing on the papers in the special issue, we ask: what are the core questions for the future of research into health law and policy, and European health law and policy more specifically? We first sketch the general functions and values of health law and policy. We then outline how these functions and values are affected by globalisation and Europeanisation, on the one hand, and technological change and digitalisation, on the other. In light of these developments we carve out some questions for future research and the implications of this agenda for the academic community that is working on European health law and policy.


Differential regulation of gastrulation and neuroectodermal gene expression by Snail in the Drosophila embryo.
The initiation of mesoderm differentiation in the Drosophila embryo requires the gene products of twist and snail. In either mutant, the ventral cell invagination during gastrulation is blocked and no mesoderm-derived tissue is formed. One of the functions of Snail is to repress neuroectodermal genes and restrict their expressions to the lateral regions. The derepression of the neuroectodermal genes into the ventral region in snail mutant is a possible cause of defects in gastrulation and in mesoderm differentiation. To investigate such possibility, we analysed a series of snail mutant alleles. We found that different neuroectodermal genes respond differently in various snail mutant background. Due to the differential response of target genes, one of the mutant alleles, V2, that has reduced Snail function showed an intermediate phenotype. In V2 embryos, neuroectodermal genes, such as single-minded and rhomboid, are derepressed while ventral invagination proceeds normally. However, the differentiation of these invaginated cells into mesodermal lineage is disrupted. The results suggest that the establishment of mesodermal cell fate requires the proper restriction of neuroectodermal genes, while the ventral cell movement is independent of the expression patterns of these genes. Together with the data showing that the expression of some ventral genes disappear in snail mutants, we propose that Snail may repress or activate another set of target genes that are required specifically for gastrulation.


Biological observations on the bristly catshark Bythaelurus hispidus from deep waters off the south-west coast of India.
Biological data are presented for the poorly known bristly catshark Bythaelurus hispidus based on specimens collected from the by-catch of the commercial deep-sea shrimp trawl fishery operating in the Arabian Sea at depths of 200-500 m off the south-west coast of India. One hundred and sixty-two individuals, which ranged from 120 to 366 mm total length (L(T)), were collected for this study. Size-at-maturity (L₅₀) for females and males was estimated at 252 and 235 mm L(T), respectively. The reproductive mode of B. hispidus was aplacental viviparity, which is the rarest reproductive mode within the Scyliorhinidae and is considered to be the most advanced of the three reproductive modes occurring within this family. Dietary analysis of stomach contents revealed B. hispidus feeds on a variety of prey, primarily fishes.


Concurrent evaluation of data quality, reliability and validity of the Australian/Canadian Osteoarthritis Hand Index and the Functional Index for Hand Osteoarthritis.
Concurrent evaluation of data quality, internal consistency, test-retest reliability and validity of two patient-reported outcome measures (PROMs) for measuring functional impairment in hand OA (HOA); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN; 15 items) and the Functional Index of HOA (FIHOA; 10 items). Patients from an HOA cohort [n=128, mean age 68.6 (s.d. 5.8) years, 91% women] completed PROMs and performance measures during routine follow-up. One week later, a subsample (n=40) reporting no change on an HOA-specific transition question contributed with test-retest data. Both instruments had satisfactory levels of data quality, internal consistency, test-retest reliability and construct validity. The AUSCAN performed slightly better than the FIHOA relating to levels of missing data (0 vs 5%), floor effects, principal component analysis loadings (0.62-0.83 vs 0.52-0.83), item-total correlation (0.77-0.91 vs 0.45-0.76) and Cronbach's α (0.94-0.96 vs 0.90), respectively. AUSCAN items had slightly lower test-retest κ-values (0.29-0.77 vs FIHOA 0.41-0.77) and AUSCAN scales lower intra-class correlations (0.80-0.92 vs FIHOA 0.94). Correlations between the two instruments ranged from 0.58 to 0.88 for the AUSCAN scales of stiffness and physical function, respectively. AUSCAN physical function scale was generally slightly strongly correlated with the other PROMS and performance measures. The AUSCAN and the FIHOA are reliable and valid instruments suitable for measuring physical functioning in HOA. The FIHOA had higher test-retest reliability and is shorter, but the AUSCAN performed slightly better concerning data quality and construct validity.


[Some observations on high specialty medical care in Mexico].
To put forth the concept of highly specialized medical care, in agreement with the nature of its practice, and evaluate the feasibility of creating a support service network. Qualitative study of the current practice and requirements for 39 selected medical specialties, using the technique of focused groups of experts in each specialty. In accordance with the "Grounded Theory", variables were systematized and categorized and then compared in order to identify relationships between categories and link them to consensus testimonial references. On the basis of the characteristics of each kind of practice, one key expert integrated and validated service portfolios. We developed an integrated a concept for highly specialize medical care with 39 operational catalogs of those diagnoses that belong to each specialty, along with catalogs of the resources required by each specialty. Highly specialized care is a desirable model for clinical practice, but does not constitute a different level of care. Currently, medical practice is constrained by the lack of well-defined boundaries and scarcity of resources in order to be conceptualized as high specialty. It is therefore more convenient to strengthen the concept of third level of care in order to identify opportunities for the establishment of high specialty areas that will in turn serve as the focal points for medical innovation.


Left Atrial Appendage Closure Yields Favorable Cardio- and Cerebrovascular Outcomes in Patients With Non-valvular Atrial Fibrillation and Prior Stroke.
Introduction: Patients with non-valvular atrial fibrillation (NVAF) and previous stroke are at significantly higher risk of stroke recurrence. Data on the efficacy of left atrial appendage closure (LAAC) on these patients is limited. The aim of this study was to investigate the differences of LAAC efficacy on long-term cardio- and cerebrovascular outcomes in NVAF patients with vs. without prior stroke. Methods: Three hundred and seventy consecutive NVAF patients who underwent LAAC were enrolled and divided into stroke and non-stroke groups based on history of previous stroke. Endpoints, such as thromboembolism, major bleeding, and mortality post-LAAC, were followed up among groups. Results: Patients in the stroke group had higher mean CHA2DS2-VASc and HAS-BLED scores compared to the non-stroke group (5.1 vs. 3.6 and 4.1 vs. 3.4, both P < 0.001, respectively). Over a median follow-up of 2.2 years, there were no significant differences in incidence rates of thromboembolism, device-related thrombus (DRT), major bleeding, and combined efficacy endpoints between the two groups. In both stroke and non-stroke groups, LAAC decreased the risk of thromboembolism [relative risk reduction (RRR) 87.5%, P = 0.034, and 74.6%, P = 0.004, respectively] and major bleeding (RRR 68.8%, P = 0.034, and 68.6%, P = 0.007, respectively) compared with predicted risk. The RRR in thromboembolism was greater in patients with vs. without prior stroke (OR 2.45, 95% CI: 1.20-5.12, P = 0.016). The incidence rates of all-cause mortality and non-cardiovascular death were similar between the two groups, but the risks of cardiovascular death post-LAAC both before (1.4% vs. 8.1%, respectively, P = 0.038) and after adjustment for confounding factors (P = 0.048) were significantly decreased in the stroke group. Conclusions: Patients with vs. without prior stroke did not exhibit a worse clinical prognosis after LAAC. LAAC may provide an increased benefit in cardio-cerebrovascular outcomes in patients with previous stroke compared to those without previous stroke. Further research is necessary to evaluate the efficacy of LAAC in this field.


Deconstructing Free Energies in the Law of Matching Water Affinities.
The law of matching water affinities (LMWA) is explored in classical molecular dynamics simulations of several alkali halide ion pairs, spanning the size range from small kosmotropes to large chaotropes. The ion-ion potentials of mean force (PMFs) are computed using three methods: the local molecular field theory (LMFT), the weighted histogram analysis method (WHAM), and integration of the average force. All three methods produce the same total PMF for a given ion pair. In addition, LMFT-based partitioning into van der Waals and local and far-field electrostatic free energies and assessment of the enthalpic, entropic, and ion-water components yield insights into the origins of the observed free energy profiles in water. The results highlight the importance of local electrostatic interactions in determining the shape of the PMFs, while longer-ranged interactions enhance the overall ion-ion attraction, as expected in a dielectric continuum model. The association equilibrium constants are estimated from the smooth WHAM curves and compared to available experimental conductance data. By examining the variations in the average hydration numbers of ions with ion-ion distance, a correlation of the water structure in the hydration shells with the free energy features is found.


Comparative SWOT analysis of strategic environmental assessment systems in the Middle East and North Africa region.
This paper presents a SWOT analysis of SEA systems in the Middle East North Africa region through a comparative examination of the status, application and structure of existing systems based on country-specific legal, institutional and procedural frameworks. The analysis is coupled with the multi-attribute decision making method (MADM) within an analytical framework that involves both performance analysis based on predefined evaluation criteria and countries' self-assessment of their SEA system through open-ended surveys. The results show heterogenous status with a general delayed progress characterized by varied levels of weaknesses embedded in the legal and administrative frameworks and poor integration with the decision making process. Capitalizing on available opportunities, the paper highlights measures to enhance the development and enactment of SEA in the region.


Engineered aluminum nanoparticle induces mitochondrial deformation and is predicated on cell phenotype.
The main role of mitochondria is to generate the energy necessary for the cell to survive and adapt to different environmental stresses. Energy demand varies depending on the phenotype of the cell. To efficiently meet metabolic demands, mitochondria require a specific proton homeostasis and defined membrane structures to facilitate adenosine triphosphate production. This homeostatic environment is constantly challenged as mitochondria are a major target for damage after exposure to environmental contaminants. Here we report changes in mitochondrial structure profiles in different cell types using electron microscopy in response to particle stress exposure in three different representative lung cell types. Endpoint analyses include nanoparticle intracellular uptake; quantitation of mitochondrial size, shape, and ultrastructure; and confirmation of autophagosome formation. Results show that low-dose aluminum nanoparticles exposure (1 ppm; 1 µg/mL; 1.6 × 1 0-7 µg/cell)) to primary and asthma cells incurred significant mitochondrial deformation and increases in mitophagy, while cancer cells exhibited only slight changes in mitochondrial morphology and an increase in lipid body formation. These results show low-dose aluminum nanoparticle exposure induces subtle changes in the mitochondria of specific lung cells that can be quantified with microscopy techniques. Furthermore, within the lung, cell type by the nature of origin (i.e. primary vs. cancer vs. asthma) dictates mitochondrial morphology, metabolic health, and the metabolic stress response of the cell.


Senile dementia: a threshold phenomenon of normal aging? A contribution to the functional reserve hypothesis of the brain.
Neurochemical investigations with normal aging brains show that in the first 70 years of life no major changes of the glycolytic pathway can be observed. Only in the following decades does a significant decrease of brain metabolic turnover occur. Changes in nerve cell size, one of the most relevant parameters in evaluating a diffuse nerve cell atrophy, appear in the brain cortex not earlier than between 85 and 94 years of age; a 21% nerve cell shrinkage is the mean. The results demonstrate that a significant decrease in turnover of the glycolytic pathway is followed by a significant but moderate shrinkage of the nerve cells after a delay of 10-15 years. Similar investigations in brains from senile demented subjects demonstrate that the change in glycolytic turnover is much more a quantitative than a qualitative phenomenon. In comparison with age-matched controls a decrease in glycolytic turnover of more than 60% is observed. Morphometric investigations of the nerve cell sizes in the brain cortex of senile demented subjects showed a decrease of 45-55% when compared with age-matched controls. When normal aging is compared with senile dementia it seems that old age dementia is a threshold phenomenon which starts if the glycolytic turnover drops below 50% of its value in young healthy adults. Physiological aging, however, stays within the range of the reserve capacity of normal brain performance. In conclusion, it seems that the exhaustion of the functional reserve capacity may shift an aging brain into a dementia syndrome.


[In vitro indirect pathogenesis of Pseudomonas aeruginosa against anti MRSA chemotherapy].
In the patient with a chronic respiratory disease, both Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) are frequently detected from expectoration. Vancomycin (VCM) and arbekacin (ABK) are both recommended for the chemotherapy of MRSA infection in Japan. Minocycline (MINO) is also selected for the treatment of MRSA infection. While rifampicin (RFP) and a trimetoprim-sulfamethoxazole combination (ST) are also recommended in Europe and USA but not recommended in Japan for the chemotherapy of MRSA infection. It is pointed out that coexistence bacteria affect chemotherapy as an indirect pathogen. Not only an antibacterial action but the immunological action or the metabolic effect against chronic P. aeruginosa infection such as DPB is known by the administration of 14-membered ring macrolides including erythromycin (EM). We considered the influence of P. aeruginosa isolated with MRSA on the activity against anti-MRSA agents by the disk diffusion method with bilayer flat agar in vitro. Moreover, we also examined the influence of EM against the activity of the anti-MRSA agents when P. aeruginosa was coexistence. One strain of MRSA as an indicator strain and 100 strains of P. aeruginosa as test strains, which were obtained from clinical materials, were used for the following experiment. P. aeruginosa was streaked on to the Mueller-Hinton agar culture medium (MHA), and they incubated at 35 degrees C for 24 hours. Then, the blood agar plate was piled up, MRSA was streaked on the blood agar surface, the susceptibility test disks (VCM, ABK, MINO, RFP, ST) were put on it, and incubated at 35 degrees C for a further 24 hours. The diameter of the zone of inhibition around the susceptibility disks against MRSA was measured and compared with P. aeruginosa free experiments. The anti-MRSA activity of MINO, ST and ABK was reduced by coexistence of P. aeruginosa. In RFP and VCM, the anti-MRSA activity was reinforced by coexistence of P. aeruginosa. Although the anti-MRSA activity of ST and ABK has improved by EM addition in the MHA plates, the anti-MRSA activity has not improved in MINO. These results are suggesting that in a MRSA infection, the chemotherapy by anti-MRSA agents were affected by coexistence of P. aeruginosa as an indirect pathogen. The macrolides such as EM may be useful as a modulator for chemotherapy by ST or ABK when MRSA and P. aeruginosa are isolated at the same time from the patient.


Usefulness of colon targeted DHA and EPA as novel diabetes medications that promote intrinsic GLP-1 secretion.
Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted from intestinal L-cells and now considered as an ideal diabetic medicine. Recently, it was reported that the unsaturated fatty acid alpha-linoleic acid promotes the secretion of GLP-1 via a G protein-coupled receptor, GPR120. However, the effects of long-chain polyunsaturated fatty acids on the secretion of GLP-1 have not been examined in vivo. The aim of this study was to evaluate the effects of the long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on blood glucose levels, plasma insulin, and GLP-1 concentrations. In addition, site-specific differences in these effects were determined using several intestinal segments: stomach, jejunum, and colon. After an intraperitoneal glucose administration (1.5 mg/g weight), each mouse was administered vehicle or an alpha-linoleic acid, DHA, EPA or EPA ester (EPA-E) solution to each intestinal segment. After an intraperitoneal glucose challenge, marked endogenous GLP-1 secretion, substantial insulin release and subsequent glucose reductions were observed in the intracolonic DHA and EPA treatment groups. In contrast, DHA and EPA did not increase GLP-1 secretion when given in the other segments. These data suggested that the colon-specific delivery of DHA, EPA, and possibly EPA-E would be a novel antidiabetic treatment by the stimulation of intrinsic GLP-1 secretion.


Gender, knowledge about AIDS, reported behavioral change, and the sexual behavior of college students.
This article reports on an analysis of the relationships among knowledge about AIDS, self-reported changes in sexual behavior, and independent measures of those behaviors--condom use, coital frequency, and number of partners. The sample consisted of 195 sexually active, heterosexual college students attending a northeastern state university in spring 1988. With other relevant variables held constant, statistically significant associations in the predicted direction were found between knowledge and reported change and each of the dependent variables among the men, especially the men not involved in relationships. Among women, however, the only significant association was that between reporting the beginning of condom use and the frequency with which condoms were used in the past year. Possible reasons for these gender differences are discussed.


Cognitive function after systemic therapy for breast cancer.
An underinvestigated area of breast cancer survivorship involves the possible impairment of cognitive function following adjuvant chemohormonal therapy. Numerous reports of disturbing and disruptive changes in short- and long-term memory, attention span, concentration, and language skills have been made by breast cancer patients who have received chemotherapy. This article reviews the four published studies that have documented cognitive dysfunction following adjuvant chemohormonal therapies commonly used in breast cancer. The studies describe a subset of approximately one-third of participants who experienced long-term cognitive impairment. Patient- and treatment-related factors that may influence cognitive function are outlined. The impact of these cognitive impairments on the individual breast cancer survivor's quality of life is discussed, as is the potential overall impact of this research on future adjuvant therapy. The need for a prospective longitudinal study documenting the neuropsychological sequelae of adjuvant chemohormonal therapy is emphasized.


High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry.
The neutralizing activity of anti-hepatitis C virus (HCV) antibodies is attenuated by a factor present in human sera, which has been proposed to be high-density lipoproteins (HDLs). HDLs have also been shown to facilitate the entry of HCV pseudoparticles (HCVpp) into target cells. Here, the aim of the study was to determine whether HDL-mediated facilitation of HCVpp and infectious HCV (HCVcc) entry and attenuation of neutralization are two related phenomena. The data indicated that HDLs attenuate neutralization at a constant rate. In addition, as for HDL-mediated facilitation of HCVpp entry, attenuation of neutralization depended on the expression of the scavenger receptor BI (SR-BI) and its selective lipid-uptake function. Finally, kinetic experiments showed that HDL-mediated facilitation of HCVpp entry is more rapid than virus neutralization. Altogether, these observations indicate that HCV is exploiting the physiological activity of SR-BI for promoting its entry into target cells, which consequently also protects the virus against neutralizing antibodies.


A Multiloculated Left Ventricular Thrombus.
A 50-year-old-man presented with worsening heart failure. He had suffered an anterior wall myocardial infarction nine years prior and had severe left ventricular dysfunction. On transthoracic echocardiography a mass was seen attached on akinetic left ventricular apex with multiple internal hypoechoic loculations, suggestive of a left ventricular thrombus.


A nuclear marker for mammalian cells and its use with intracerebral transplants.
The Hoechst dye staining method has been successfully applied to the central nervous system in mammals and its use has been demonstrated in intracerebral transplantation. The technique is rapid, simple and based on intrinsic nuclear properties. It was found to be permanent and valid whatever the animal strains or ages, allowing the distinction of rat cells from those of mouse, studied either separately or in a cross-transplantation model. It permitted the detection of grafted cells in the area of transplantation and the observation of early dispersion around the implantation site. Moreover, it can be combined with immunohistochemistry as demonstrated by a myelin marker in a relevant model. Immunodetection can thus help to directly observe grafted cells, at distance from the locus of transplantation, confirming their presence in the graft-type myelin patches. Because of its rapid performance, this technique can be used systematically after transplantation to check for the presence of grafted cells in the host.