Radiopharmaceutical dosage selection for pediatric nuclear medicine.
To identify the most rational method for adjusting adult radiopharmaceutical dosages for children, four methods of dosage computation were examined from the perspectives of diagnostic adequacy and radiation absorbed dose. For static imaging, information density is the most important factor in study quality, and adjustment of dosage by body weight (Wt) for "thick" organs, and body surface area (BSA) for "thin" organs is recommended. Compared with adults, small children receive less radiation exposure if radiopharmaceutical dosages are adjusted by Wt, and slightly greater exposure if dosages are adjusted by BSA. For dynamic imaging studies, dosage requirements are governed by the spatial resolution needed for region of interest assignment, and the statistical reliability of the time-activity data. For dynamic renal imaging, renograms of similar quality are obtained if dosages are adjusted by height (Ht). Dynamic cardiac studies might appear to require dosages even larger than those adjusted by Ht which would result in higher radiation absorbed doses to pediatric patients. However, smaller dosages can be used in children by prolonging the imaging time and accepting lower temporal resolution. Dosage requirements for dynamic studies depend on which physiologic characteristics are measured from the time-activity data. Since the measurements of some characteristics demand higher count rates than others, dosage requirements ultimately depend on which measurements are clinically necessary. Close attention to the factors that determine these requirements may yield significant reduction in dosages, and thus in radiation exposure, for patients of all ages.


Sarcoidosis--immunopathogenetic concepts.
Sarcoidosis is a chronic granulomatous disorder characterized by an accumulation of activated lymphocytes, predominantly T helper cells, expressing the Th1 phenotype and macrophages at sites of disease activity. Although the cause of sarcoidosis has not been elucidated, several lines of evidence suggest that granuloma formation results from exposure to one or more antigens, eliciting a T lymphocyte response. The induction and evolution of granuloma formation results from a complex interplay between diverse cell types, cytokines, and chemokines. Genetic polymorphisms may influence the clinical expression of the granuloma formation and disease outcome. This article discusses in depth the key cellular elements and signals that generate and orchestrate the sarcoid granulomatous response. The precise factors inciting the sarcoid granulomatous response have not yet been identified, but chronic exposure to microbial agents, their products, or inorganic substances may be important in the pathogenesis.


Oxidative damage, skin aging, antioxidants and a novel antioxidant rating system.
It is believed that oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to neutralize the reactive intermediates. Oxidative damage occurs because of both intrinsic and extrinsic mechanisms. Together, intrinsic and extrinsic damage are the primary causes of skin aging. The skin uses a series of intrinsic antioxidants to protect itself from free radical damage. Naturally occurring extrinsic antioxidants have also been widely shown to offset and alleviate these changes. Unlike sunscreens, which have an SPF rating system to guide consumers in their purchases, there is no widely accepted method to choose antioxidant anti-aging products. ORAC (Oxygen Radical Absorbance Capacity) and ABEL-RAC (Analysis By Emitted Light-Relative Antioxidant Capacity), are both accepted worldwide as a standard measure of the antioxidant capacity of foods, and are rating systems that could be applied to all antioxidant skincare products. The standardization of antioxidant creams could revolutionize the cosmeceutical market and give physicians and consumers the ability to compare and choose effectively.


The effects of interferon-alpha on the production and action of other cytokines.
Various interferon-alpha (IFN-alpha) preparations, either as individual subtypes or natural mixtures, induce or inhibit expression of several other cytokines, as well as cytokine receptors and chemokines. The cytokines and receptors reportedly affected by IFN-alpha include interleukin-1 (IL-1), IL-2, IL-6, IL-8, IL-1 receptor, IL-1 receptor antagonist, tumor necrosis factor, tumor necrosis factor receptor, and IFN-gamma, all of which may amplify the effects of IFN-alpha treatment. The mechanism by which IFN-alpha induces expression of these cytokines is not clear. Some of the therapeutic and toxic effects associated with IFN-alpha therapy may be caused by the induction or inhibition of other cytokines and their respective cellular effects. Side effects including fever, anorexia, and fatigue can be caused by one or more of the cytokines induced by IFN-alpha. The response of different cell types, normal or malignant, to cytokines can vary. Such variation in cell type-specific responses may contribute to the diverse array of physiologic effects associated with IFN-alpha therapy. Further research is required to systematically uncover how other cytokines, receptors, or cellular factors contribute to the therapeutic and toxic effects of IFN-alpha.


Topical Fluorouracil Therapy for Residual Superficial Basal Cell Carcinoma Following Mohs Micrographic Surgery.
When treating invasive basal cell carcinoma (BCC) with Mohs micrographic surgery (MMS), including infiltrative and nodular subtypes, the goal is complete surgical removal of the tumor. In some cases, after several stages of MMS, residual foci of superficial BCC are noted with no dermal invasive components apparent. Some patients and surgeons have opted for halting surgery and treating residual superficial BCC with adjuvant topical fluorouracil. In this retrospective study, this treatment method is shown to be effective with a recurrence rate of BCC of 3.7% over a mean follow up of 28 months. This treatment method reduces the number of stages of MMS as the surgery is stopped was invasive BCC is removed. This can be beneficial when considering the morbidity of prolonged surgical procedures in frail, elderly patients experiencing surgical fatigue, the cost of additional stages, and the cost of advanced repairs due to enlarging defect size. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.4811.


Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knockout mice.
The relationship between metabolism and reactive oxygen species (ROS) production by the mitochondria has often been (wrongly) viewed as straightforward, with increased metabolism leading to higher generation of pro-oxidants. Insights into mitochondrial functioning show that oxygen consumption is principally coupled with either energy conversion as ATP or as heat, depending on whether the ATP-synthase or the mitochondrial uncoupling protein 1 (UCP1) is driving respiration. However, these two processes might greatly differ in terms of oxidative costs. We used a cold challenge to investigate the oxidative stress consequences of an increased metabolism achieved either by the activation of an uncoupled mechanism (i.e. UCP1 activity) in the brown adipose tissue (BAT) of wild-type mice or by ATP-dependent muscular shivering thermogenesis in mice deficient for UCP1. Although both mouse strains increased their metabolism by more than twofold when acclimatised for 4 weeks to moderate cold (12°C), only mice deficient for UCP1 suffered from elevated levels of oxidative stress. When exposed to cold, mice deficient for UCP1 showed an increase of 20.2% in plasmatic reactive oxygen metabolites, 81.8% in muscular oxidized glutathione and 47.1% in muscular protein carbonyls. In contrast, there was no evidence of elevated levels of oxidative stress in the plasma, muscles or BAT of wild-type mice exposed to cold despite a drastic increase in BAT activity. Our study demonstrates differing oxidative costs linked to the functioning of two highly metabolically active organs during thermogenesis, and advises careful consideration of mitochondrial functioning when investigating the links between metabolism and oxidative stress.


Detection of a novel, primate-specific 'kill switch' tumor suppression mechanism that may fundamentally control cancer risk in humans: an unexpected twist in the basic biology of TP53.
The activation of TP53 is well known to exert tumor suppressive effects. We have detected a primate-specific adrenal androgen-mediated tumor suppression system in which circulating DHEAS is converted to DHEA specifically in cells in which TP53 has been inactivated DHEA is an uncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD), an enzyme indispensable for maintaining reactive oxygen species within limits survivable by the cell. Uncompetitive inhibition is otherwise unknown in natural systems because it becomes irreversible in the presence of high concentrations of substrate and inhibitor. In addition to primate-specific circulating DHEAS, a unique, primate-specific sequence motif that disables an activating regulatory site in the glucose-6-phosphatase (G6PC) promoter was also required to enable function of this previously unrecognized tumor suppression system. In human somatic cells, loss of TP53 thus triggers activation of DHEAS transport proteins and steroid sulfatase, which converts circulating DHEAS into intracellular DHEA, and hexokinase which increases glucose-6-phosphate substrate concentration. The triggering of these enzymes in the TP53-affected cell combines with the primate-specific G6PC promoter sequence motif that enables G6P substrate accumulation, driving uncompetitive inhibition of G6PD to irreversibility and ROS-mediated cell death. By this catastrophic 'kill switch' mechanism, TP53 mutations are effectively prevented from initiating tumorigenesis in the somatic cells of humans, the primate with the highest peak levels of circulating DHEAS. TP53 mutations in human tumors therefore represent fossils of kill switch failure resulting from an age-related decline in circulating DHEAS, a potentially reversible artifact of hominid evolution.


Geographic Variation in Maternal Smoking during Pregnancy in the Missouri Adolescent Female Twin Study (MOAFTS).
Despite well-known adverse health effects of maternal smoking during pregnancy (MSP), it is still unclear if MSP varies geographically and if neighborhood socioeconomic deprivation (SED) plays an important role in MSP. This study aims to investigate small-area geographic variation in MSP and examine the association of SED with MSP. The Missouri Adolescent Female Twin Study (MOAFTS) is a cohort study of female like-sex twins born in Missouri to Missouri-resident parents during 1975-1985. Biological mothers completed a baseline interview in 1995-1998 and reported MSP with the twins. Residential address of the mother at birth was geocoded. We developed a census tract-level SED index using a common factor approach based on 21 area-level socioeconomic variables from the 1980 Census data. Multilevel logistic regressions estimated geographic heterogeneity (random effect) in MSP and the odds ratios (ORs, fixed effects) of neighborhood SED associated with MSP. Of 1658 MOAFTS mothers, 35.2% reported any MSP and 21.9% reported MSP beyond the first trimester. Neighborhood SED was associated with any MSP (the highest vs. the lowest quartile: OR = 1.90, 95% confidence interval [CI] = 1.40-2.57, Ptrend<0.001) and MSP beyond the first trimester (OR = 1.98, 95% CI = 1.38-2.85, Ptrend = 0.002) in unadjusted analyses. After adjusting for individual covariates (demographics, socioeconomic conditions, alcohol use, and parents' cohabitation), neighborhood SED was not associated with MSP, but geographic variation still persisted in MSP (variance = 0.41, P = 0.003) and in MSP beyond the first trimester (variance = 0.82, P<0.001). Neighborhood SED was associated with MSP in unadjusted analyses but this association could be explained by individual socioeconomic conditions. Nonetheless, significant geographic variation in MSP persisted and was not accounted for by differences in neighborhood SED. To develop effective interventions to reduce MSP, further studies are necessary to explore underlying reasons for its geographic variation.


Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug therapy through the ABCC1 transporter.
The poor response to drug therapy often seen in hepatocellular carcinoma requires insight into the molecular interplay responsible for intrinsic or acquired drug resistance. We previously demonstrated that the CD133-/EpCAM- subpopulation of the Huh-7 hepatoma cell line features aberrant activation of the hedgehog signaling (Hh) pathway and chemoresistance. The prevailing hypothesis of the present study is that hedgehog signaling may govern expression of ATP-binding cassette (ABC) transporters, which are responsible for drug resistance in the CD133-/EpCAM- subpopulation. Our aim is to reveal the molecular interplay in the mediation of drug resistance with a newly established Huh-7 subpopulation featuring high Hh signaling activity and drug resistance. In this study, chemoresistance was determined in a newly established Huh-7-DN subpopulation featuring the CD133-/EpCAM- surface marker profile, aberrant expression of Hh pathway, and epithelial-mesenchymal transition (EMT). Expression of ABC transporter proteins (ABCB1, ABCC1, and ABCG2) and Hh transcription factor Gli-1/2 was evaluated with and without Hh signaling antagonists LDE225 or itraconazole. We found that hedgehog signaling activity as determined by transfection with a Gli-Lux reporter cassette and gene expression levels tended to increase from Huh-7 CD133+/EpCAM+ to CD133-/EpCAM-, and the highest levels were found in Huh-7-DN cells. The Huh-7-DN subpopulation exhibited characteristics of EMT as evidenced by increased expression of vimentin and loss of E-cadherin. Sorafenib significantly inhibited the viability of all subpopulations except the Huh-7-DN subpopulation. Compared with other sorafenib-sensitive subpopulations, the Huh-7-DN subpopulation showed enhanced expression of Hh transcription factor Gli-2 and ABCC1 transporter protein. Silencing Gli-2 by lentivirus harboring shRNA against Gli-2 or LDE225 significantly suppressed expression of Gli-2 and ABCC1 genes in Huh-7-DN subpopulation. In conclusion, aberrant hedgehog signaling activation is linked to poor differentiation, epithelial-mesenchymal transition, and chemoresistance in the Huh-7-DN subpopulation. Hedgehog signaling transcription factor Gli-2 appears to be the primary regulator for drug sensitivity of hepatoma through the ABCC1 transporter.


American Clinical Neurophysiology Society: EEG Guidelines Introduction.
This revision to the EEG Guidelines is an update incorporating current EEG technology and practice. "Standards of practice in clinical electroencephalography" (previously Guideline 4) has been removed. It is currently undergoing revision through collaboration among multiple medical societies and will become part of "Qualifications and Responsibilities of Personnel Performing and Interpreting Clinical Neurophysiology Procedures." The remaining guidelines are reordered and renumbered.


[Effects of Different Control Measures on Cadmium and Lead Accumulation and Quality in Lettuce].
To explore the safe utilization technology of farmland polluted by the heavy metals cadmium (Cd) and lead (Pb) and to realize the safe production of agricultural products, a pot experiment was conducted to investigate the effects of two soil passivators and five foliar inhibitors on Cd and Cd-accumulation and quality of lettuce with low Pb and Cd accumulation (KCW). The results showed that different control measures had different effects on the soil pH value of lettuce, and the application of 45 g·m-2biochar-based passivator had the most significant difference in improving the soil pH value, which was increased by 0.8 units compared with that in CK. By using 72 g·m-2 of humic acid passivator yielded notable difference in reducing the soil pH value of lettuce. A reduction of 0.25 units was achieved compared with that in CK. Among all the control measures, the application of 45 g·m-2 biocharcoal-based passivation agent had the best effect on reducing soil available Cd content, which was significantly reduced by 53% compared with that in CK, and the application of 135 g·m-2biocharcoal-based passivation agent had the best effect on reducing soil available Pb content, which was significantly reduced by 64% compared with that in CK. Spraying 0.8% FAK-Zn foliar inhibitor not only had the best control effect on reducing Cd and Pb contents in the edible parts of lettuce, which were significantly reduced by 77% and 60%, respectively, compared with that in CK, but it also significantly reduced Cd and Pb enrichment coefficients and transport coefficients from the root to the edible parts of the lettuce. Different control measures had different effects on the nutritional quality of lettuce, and 0.4% FAK-Zn foliar inhibitor had the best effect on soluble protein. The 0.6% FAK-Zn had the best effect on soluble sugar, and the 0.4% FAK-Zn inhibitor had the best effect on vitamin C content. The application of biocarbon-based passivator could effectively repair lettuce soil polluted by Cd and Pb, whereas the application of FAK-Zn leaf surface inhibitor could effectively inhibit the accumulation, absorption, and transfer of Cd and Pb in lettuce; improve the nutritional quality of lettuce; provide a theoretical basis for safe production of vegetables polluted by heavy metals; and promote the recycling of resources and environment.


The effect of microcolony size, at time of irradiation, on colony forming ability.
To investigate the effect of irradiating microcolonies of various sizes on their subsequent ability to form colonies. The location of individual HPV-G cells in tissue culture flasks was recorded using computerized microscopy. This allowed the cells' positions to be continually revisited, which enabled manual sizing of individual microcolonies both at the time of irradiation (between 0-5 Gy) and following an incubation period during which the microcolonies were assessed for cologenic survival. The experiments indicate that when irradiated as microcolonies, cells have plating efficiencies (PE) that are lower than expected when compared with the prediction from the PE values of cells irradiated individually. These data support the conclusions of Mothersill and Seymour (1997b) which challenge the concept of independent survival of certain types of cells following irradiation. The results indicate that interactions between cells can occur even in small aggregates.


Interventions to reduce tobacco use in people experiencing homelessness.
Populations experiencing homelessness have high rates of tobacco use and experience substantial barriers to cessation. Tobacco-caused conditions are among the leading causes of morbidity and mortality among people experiencing homelessness, highlighting an urgent need for interventions to reduce the burden of tobacco use in this population. To assess whether interventions designed to improve access to tobacco cessation interventions for adults experiencing homelessness lead to increased numbers engaging in or receiving treatment, and whether interventions designed to help adults experiencing homelessness to quit tobacco lead to increased tobacco abstinence. To also assess whether tobacco cessation interventions for adults experiencing homelessness affect substance use and mental health. We searched the Cochrane Tobacco Addiction Group Specialized Register, MEDLINE, Embase and PsycINFO for studies using the terms: un-housed*, homeless*, housing instability, smoking cessation, tobacco use disorder, smokeless tobacco. We also searched trial registries to identify unpublished studies. Date of the most recent search: 06 January 2020. We included randomized controlled trials that recruited people experiencing homelessness who used tobacco, and investigated interventions focused on the following: 1) improving access to relevant support services; 2) increasing motivation to quit tobacco use; 3) helping people to achieve abstinence, including but not limited to behavioral support, tobacco cessation pharmacotherapies, contingency management, and text- or app-based interventions; or 4) encouraging transitions to long-term nicotine use that did not involve tobacco. Eligible comparators included no intervention, usual care (as defined by the studies), or another form of active intervention. We followed standard Cochrane methods. Tobacco cessation was measured at the longest time point for each study, on an intention-to-treat basis, using the most rigorous definition available. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study where possible. We grouped eligible studies according to the type of comparison (contingent reinforcement in addition to usual smoking cessation care; more versus less intensive smoking cessation interventions; and multi-issue support versus smoking cessation support only), and carried out meta-analyses where appropriate, using a Mantel-Haenszel random-effects model. We also extracted data on quit attempts, effects on mental and substance-use severity, and meta-analyzed these outcomes where sufficient data were available. We identified 10 studies involving 1634 participants who smoked combustible tobacco at enrolment. One of the studies was ongoing. Most of the trials included participants who were recruited from community-based sites such as shelters, and three included participants who were recruited from clinics. We judged three studies to be at high risk of bias in one or more domains. We identified low-certainty evidence, limited by imprecision, that contingent reinforcement (rewards for successful smoking cessation) plus usual smoking cessation care was not more effective than usual care alone in promoting abstinence (RR 0.67, 95% CI 0.16 to 2.77; 1 trial, 70 participants). We identified very low-certainty evidence, limited by risk of bias and imprecision, that more intensive behavioral smoking cessation support was more effective than brief intervention in promoting abstinence at six-month follow-up (RR 1.64, 95% CI 1.01 to 2.69; 3 trials, 657 participants; I2 = 0%). There was low-certainty evidence, limited by bias and imprecision, that multi-issue support (cessation support that also encompassed help to deal with other challenges or addictions) was not superior to targeted smoking cessation support in promoting abstinence (RR 0.95, 95% CI 0.35 to 2.61; 2 trials, 146 participants; I2 = 25%). More data on these types of interventions are likely to change our interpretation of these data. Single studies that examined the effects of text-messaging support, e-cigarettes, or cognitive behavioral therapy for smoking cessation provided inconclusive results. Data on secondary outcomes, including mental health and substance use severity, were too sparse to draw any meaningful conclusions on whether there were clinically-relevant differences. We did not identify any studies that explicitly assessed interventions to increase access to tobacco cessation care; we were therefore unable to assess our secondary outcome 'number of participants receiving treatment'. There is insufficient evidence to assess the effects of any tobacco cessation interventions specifically in people experiencing homelessness. Although there was some evidence to suggest a modest benefit of more intensive behavioral smoking cessation interventions when compared to less intensive interventions, our certainty in this evidence was very low, meaning that further research could either strengthen or weaken this effect. There is insufficient evidence to assess whether the provision of tobacco cessation support and its effects on quit attempts has any effect on the mental health or other substance-use outcomes of people experiencing homelessness. Although there is no reason to believe that standard tobacco cessation treatments work any differently in people experiencing homelessness than in the general population, these findings highlight a need for high-quality studies that address additional ways to engage and support people experiencing homelessness, in the context of the daily challenges they face. These studies should have adequate power and put effort into retaining participants for long-term follow-up of at least six months. Studies should also explore interventions that increase access to cessation services, and address the social and environmental influences of tobacco use among people experiencing homelessness. Finally, studies should explore the impact of tobacco cessation on mental health and substance-use outcomes.


Figure-Ground Organization in Natural Scenes: Performance of a Recurrent Neural Model Compared with Neurons of Area V2.
A crucial step in understanding visual input is its organization into meaningful components, in particular object contours and partially occluded background structures. This requires that all contours are assigned to either the foreground or the background (border ownership assignment). While earlier studies showed that neurons in primate extrastriate cortex signal border ownership for simple geometric shapes, recent studies show consistent border ownership coding also for complex natural scenes. In order to understand how the brain performs this task, we developed a biologically plausible recurrent neural network that is fully image computable. Our model uses local edge detector ( B ) cells and grouping ( G ) cells whose activity represents proto-objects based on the integration of local feature information. G cells send modulatory feedback connections to those B cells that caused their activation, making the B cells border ownership selective. We found close agreement between our model and neurophysiological results in terms of the timing of border ownership signals (BOSs) as well as the consistency of BOSs across scenes. We also benchmarked our model on the Berkeley Segmentation Dataset and achieved performance comparable to recent state-of-the-art computer vision approaches. Our proposed model provides insight into the cortical mechanisms of figure-ground organization.


Extending the floor and the ceiling for assessment of physical function.
To improve the assessment of physical function by enhancing precision of physical function assessment as it pertains to subjects at extreme ends of the health continuum (i.e., subjects with extremely poor function ["floor"] or extremely good health ["ceiling"]). Under the Patient-Reported Outcomes Measurement Information System (PROMIS) (a National Institutes of Health initiative), we developed new items to assess floor and ceiling physical function in order to supplement the existing item bank. Using item response theory and standard PROMIS methodology, we developed 31 floor items and 31 ceiling items and administered the items during a 12-month prospective, observational study of 737 subjects whose health status was at either extreme. Effect size was calculated and change over time was compared across anchor instruments and across items. Using the observed changes in scores, we back-calculated sample size requirements for the new and comparison measures. We studied 444 subjects who had been diagnosed as having a chronic illness and/or were of old age and 293 generally fit subjects (including athletes in training). Item response theory analyses confirmed that the new floor and ceiling items outperformed reference items (P < 0.001). The estimated post hoc sample size requirements were reduced by a factor of 2-4 for the floor population and a factor of 2 for the ceiling population. Extending the range of items by which physical function is measured can substantially improve measurement quality, reduce sample size requirements, and improve research efficiency. The paradigm shift from assessing disability to assessing physical function focuses assessment on the entire spectrum of physical function, signals improvement in the conceptual base of outcome assessment, and may be transformative as medical goals more closely approach societal goals for health.


[Bone tissue: rebuilding and inflammation].
In this review the author summarizes the knowledge related to structural elements of bone tissue. The process of bone reorganisation and knowledge about the special feature of bone metabolism in human are also discussed. It is noted that due to the reorganisation, there is a complete renewal of bone tissue in every 10 years, and this renewal lasts throughout the life. However, there are life periods when osteoclast activity is low, e.g. in childhood and the second decade of life when the gain of bone mass may be as much as 40% of the final bone mass. Overactivity of osteoclasts occurs at age 60 years in men and somewhat earlier in women. Reorganization of bone tissue is an elementary requirement for the physiological functions (locomotion, hemopoiesis, immune functions). The RANK-RANKL-osteoprotegerin axis plays an important role in the regulation of bone metabolism. Bone mass is dependent on osteocytes; osteoblasts are building up while osteoclasts are reabsorbing bone tissue. In this process transcription factors, hormone-like substances and a large number of cytokines are involved. In addition, the inflammatory process within the bone tissue as well as the defending, reparative inflammation and specific immune response are of great importance in bone reorganisation. This is particularly valid for α2-macroglobulin and transforming growth factor, although the exact role in bone reorganization has not been fully explored. It can be concluded that the elements, which participate in bone reorganization and in defending inflammatory and specific immunological processes, are essentially identical. Therefore, the existence of an osteo-immunological complex system has emerged.


Healthcare-related stigma among men who have sex with men and transgender women in sub-Saharan Africa participating in HIV Prevention Trials Network (HPTN) 075 study.
ABSTRACT The inability to access health services when needed is a critical barrier to HIV prevention, treatment and care among men who have sex with men (MSM) and transgender women (TGW). Using data collected in HPTN 075, we explored factors associated with any experienced healthcare-related stigma. HPTN 075 was a cohort study to assess the feasibility of recruiting and retaining MSM and TGW in clinical trials in sub-Saharan Africa. Of 401 MSM and TGW enrolled at four sites (Kisumu, Kenya; Blantyre, Malawi; Cape Town, Soweto, South Africa) 397 contributed to the analysis (79.9% cis-gender and 20.1% TGW). Of these, (45.3%; 180/397) reported one or more of healthcare-related stigma experiences. Most frequently reported experiences included fear to seek healthcare services (36.3%) and avoiding seeking such services because of the discovery of MSM status (29.2%). Few men and TGW (2.5%) reported having been denied health services because of having sex with men. In multivariable analysis, more participants in Soweto [adjusted odds ratio (AOR) = 2.60] and fewer participants in Blantyre (AOR = 0.27) reported any healthcare-related stigma experiences, in comparison to participants in Kisumu. MSM and TGW that did not have a supportive gay community to rely on were more likely to report any healthcare-related stigma experiences (AOR = 1.46), whereas MSM and TGW who reported high social support and who never had engaged in transactional sex were less likely to report such experiences (AOR = 0.76 and AOR = 0.43, respectively). Our results suggest that encouraging support groups for MSM and TGW as well as training and sensitizing healthcare staff, and the general community, on MSM and TGW health issues and cultural competence may reduce stigma, improve access to healthcare, which could ultimately reduce HIV transmission.


[The principles of diagnosing hereditary pathology].
The paper is concerned with advances of clinical genetics in the diagnosis of hereditary diseases. Emphasis is laid on substantial contribution of heredity to the pathology of the fetus, neonate, child and adult. Diagnostic potentialities of antenatal, neonatal and postnatal diagnosis are characterized. Contribution of heredity to the impairment of reproductive functions in women is discussed.


Radiographic identification of the equine ventral conchal bulla.
Involvement of the ventral conchal sinus (VCS) is an important diagnostic and prognostic feature in cases of the equine sinus disease. The authors aimed to ascertain if the caudo-dorsal extension of the VCS, the ventral conchal bulla (VCB) is identifiable on plain radiographs of cadaver skulls without sinus disease. Bilateral frontonasal sinus flaps were made in 10 equine cadaver skulls. Plain lateral, lateral oblique and dorso-ventral radiographs were then obtained followed by the same views taken with stainless steel wire outlining the caudal border of the VCB. Plain radiographs were randomised and blindly evaluated by two observers who marked where they believed the VCB to be positioned. This was then correlated with the true position of the VCB using radiographs with wires in place. The ease of identification of the VCB was classified as 'easy' or 'difficult'. The VCB was correctly identified in 70 per cent of lateral radiographs, but only 45 per cent of lateral oblique radiographs and 17 per cent of dorso-ventral radiographs. If a clinician was confident that he or she could identify the VCB, they were usually correct. Conversely if the clinician judged VCB identification as 'difficult', they usually identified it incorrectly. In the authors' clinical experience, the VCB of horses with sinusitis involving this compartment is more radiologically evident than in clinically normal horses. Knowledge of the normal radiographic anatomy of this structure should aid clinicians in identifying horses with sinusitis affecting the VCS.


Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women.
We have previously described differences in adipose cell size distribution and expression of genes related to adipocyte differentiation in subcutaneous abdominal fat obtained from insulin-sensitive (IS) and -resistant (IR) persons, matched for degree of moderate obesity. To determine whether other biological properties also differ between IR and IS obese individuals, we quantified markers of inflammatory activity in adipose tissue from overweight IR and IS individuals. Subcutaneous abdominal tissue was obtained from moderately obese women, divided into IR (n = 14) and IS (n = 19) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Inflammatory activity was assessed by comparing expression of nine relevant genes and by immunohistochemical quantification of CD45- and CD68-containing cells. SSPG concentrations were approximately threefold higher in IR than in IS individuals. Expression levels of CD68, EMR1, IL8, IL6 and MCP/CCL2 mRNAs were modestly but significantly increased (p < 0.05) in IR compared with IS participants. Results of immunohistochemical staining were consistent with gene expression data, demonstrating modest differences between IR and IS individuals. Crown-like structures, in which macrophages surround single adipocytes, were rarely seen in tissue from either subgroup. A modest increase in inflammatory activity was seen in subcutaneous adipose tissue from IR compared with equally obese IS individuals. Together with previous evidence of impaired adipose cell differentiation in IR vs equally obese individuals, it appears that at least two biological processes in subcutaneous adipose tissue characterize the insulin-resistant state independent of obesity per se.


Repurposing drugs for the management of COVID-19.
Introduction: The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 represents a serious health issue worldwide, with more than 61 million cases and more than 1.4 million deaths since the beginning of the epidemic near the end of 2019. The scientific community strongly responded to this emergency situation with massive research efforts, mostly focused on diagnosis and clinical investigation of therapeutic solutions. In this scenario, drug repurposing played a crucial role in accelerating advanced clinical testing and shortening the time to access the regulatory review.Areas covered: This review covers the main and most successful drug repurposing approaches from a design, clinical, and regulatory standpoint. Available patents on repurposed drugs are also discussed.Expert opinion: Drug repurposing proved highly successful in response to the current pandemic, with remdesivir becoming the first specific antiviral drug approved for the treatment of COVID-19. In parallel, a number of drugs such as corticosteroids and low molecular weight heparin (LMWH) are used to treat hospitalized COVID-19 patients, while clinical testing of additional therapeutic options is ongoing. It is reasonably expected that these research efforts will deliver optimized and specific therapeutic tools that will increase the preparedness of health systems to possible future epidemics.


Optimizing and Individualizing the Pharmacological Treatment of First-Episode Schizophrenic Patients: Study Protocol for a Multicenter Clinical Trial.
Introduction: Affecting ~1% of the world population, schizophrenia is known as one of the costliest and most burdensome diseases worldwide. Antipsychotic medications are the main treatment for schizophrenia to control psychotic symptoms and efficiently prevent new crises. However, due to poor compliance, 74% of patients with schizophrenia discontinue medication within 1.5 years, which severely affects recovery and prognosis. Through research on intra and interindividual variability based on a psychopathology-neuropsychology-neuroimage-genetics-physiology-biochemistry model, our main objective is to investigate an optimized and individualized antipsychotic-treatment regimen and precision treatment for first-episode schizophrenic patients. Methods and Analysis: The study is performed in 20 representative hospitals in China. Three subprojects are included. In subproject 1, 1,800 first-episode patients with schizophrenia are randomized into six different antipsychotic monotherapy groups (olanzapine, risperidone, aripiprazole, ziprasidone, amisulpride, and haloperidol) for an 8-week treatment. By identifying a set of potential biomarkers associated with antipsychotic treatment response, we intend to build a prediction model, which includes neuroimaging, epigenetics, environmental stress, neurocognition, eye movement, electrophysiology, and neurological biochemistry indexes. In subproject 2, apart from verifying the prediction model established in subproject 1 based on an independent cohort of 1,800 first-episode patients with schizophrenia, we recruit patients from a verification cohort who did not get an effective response after an 8-week antipsychotic treatment into a randomized double-blind controlled trial with minocycline (200 mg per day) and sulforaphane (3 tables per day) to explore add-on treatment for patients with schizophrenia. Two hundred forty participants are anticipated to be enrolled for each group. In subproject 3, we tend to carry out one trial to construct an intervention strategy for metabolic syndrome induced by antipsychotic treatment and another one to build a prevention strategy for patients at a high risk of metabolic syndrome, which combines metformin and lifestyle intervention. Two hundred participants are anticipated to be enrolled for each group. Ethics and Dissemination: The study protocol has been approved by the Medical Ethics committee of the Second Xiangya Hospital of Central South University (No. 2017027). Results will be disseminated in peer-reviewed journals and at international conferences. Trial Registration: This trial has been registered on Clinicalrials.gov (NCT03451734). The protocol version is V.1.0 (April 23, 2017).


Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.
Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months. The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.


Regulation of Peptidase Activity beyond the Active Site in Human Health and Disease.
This comprehensive review addresses the intricate and multifaceted regulation of peptidase activity in human health and disease, providing a comprehensive investigation that extends well beyond the boundaries of the active site. Our review focuses on multiple mechanisms and highlights the important role of exosites, allosteric sites, and processes involved in zymogen activation. These mechanisms play a central role in shaping the complex world of peptidase function and are promising potential targets for the development of innovative drugs and therapeutic interventions. The review also briefly discusses the influence of glycosaminoglycans and non-inhibitory binding proteins on enzyme activities. Understanding their role may be a crucial factor in the development of therapeutic strategies. By elucidating the intricate web of regulatory mechanisms that control peptidase activity, this review deepens our understanding in this field and provides a roadmap for various strategies to influence and modulate peptidase activity.


Teaching cardiac auscultation using simulated heart sounds and small-group discussion.
Several educators have reported poor identification of abnormal cardiac sounds by primary care residents. Practice and review with cardiology patient simulators and prerecorded heart sounds has been shown to increase the accuracy of diagnosis by medical students and residents. The participants were 15 members of an urban family practice residency. The residents were presented with simulated heart sounds and were asked to identify them in a pretest and posttest. Between the tests, participants were invited to three separate teaching sessions that involved a discussion of cardiac auscultatory findings and a review of audiotaped similar heart sounds. Residents who were unable to attend the teaching sessions formed a control group. The pretest identification rate was 36% for the heart sounds. This improved to 62% for all residents after the intervention. Higher rates of improvement were demonstrated by the residents who attended one or more teaching sessions, compared with the residents who attended no teaching sessions. Small-group discussion and repetitive auscultation of simulated heart sounds can improve the cardiac auscultatory proficiency of family practice residents.


Photoreceptor cell specific proteins of snake pineal.
The pineal body of lower vertebrates is saccular and directly photoreceptive. The pineal gland of mammals is parenchymal and not directly photoreceptive. The parenchymal morphology of snake pineal raises questions of direct photoreceptivity of snake pineal and of correspondence of molecular homology with morphological homology. S-antigen and rhodopsin are highly conserved photoreceptor cell specific proteins. We used site-specific monoclonal antibodies (MAb) to study S-antigen and rhodopsin of snake pineal. Immunohistochemical reactivity of snake retina and pineal was compared to that of trout, guinea pig, and rat. MAb's to S-antigen reacted with each pineal and retina tested, but reactivity of individual MAb's with snake tissue was more similar to that with trout than with rat or guinea pig tissue. MAb's to rhodopsin did not react with snake pineal, although they did react with the photoreceptive trout pineal body. MAb's to rhodopsin reacted with retina of each species. These results suggest that although snake pineal is morphologically similar to mammalian pineal, and like mammalian pineal is probably not directly photoreceptive, it does have S-antigen homology with lower vertebrates such as trout.


Herpes simplex virus defective genomes: structure of HSV-1 ANG defective DNA of class II and encoded polypeptides.
Sequence organization and origin of HSV-1 strain Angelotti (ANG) class II defective DNA (HSV-1 ANG dDNA1) were examined in detail by establishing physical maps and by molecular cloning. dDNA1 consists of concatemers of tandem repeat units in which sequences from the UL region spanning map coordinates 0.37 to 0.415 of standard HSV ANG DNA are covalently linked to TRS/IRS sequences. The size of the repeat unit was determined to be about 8.9 kilobase pairs (kb), comprising sequences of 7.3 kb from UL and 1.6 kb from TRS/IRS regions. UL sequences were delineated by restriction enzyme sites KpnI N-P and EcoRI F-M, and were colinear with the corresponding sequences of the standard (wild-type) virus genome. Expression of dDNA1 was studied in African green monkey kidney cells and in Xenopus laevis oocytes. A major polypeptide of approx. mol. wt. 135 000 (135K) was overproduced, suggesting that this protein was encoded by dDNA1. By several parameters, e.g. size, immune cross-reactivity, and affinity for native and denatured DNA, the 135K polypeptide was identified as the major HSV DNA-binding protein. It was further shown that the repeat unit contains part of the DNA polymerase gene as demonstrated by its ability to rescue some mutations in this gene.


New standards in the chemotherapy of metastatic hormone-refractory prostate cancer.
Hormone-refractory prostate cancer (HRPC) is a major issue in Western countries and the second leading cause of cancer death in North American men. In the prostate-specific antigen era, most HRPCs are currently diagnosed in asymptomatic patients based on biochemical failure, with increasing demand for active treatment. Until recently, chemotherapy for HRPC patients was not considered a standard of care due to the absence of clear data evidencing an overall survival benefit. In fact, few Phase III studies conducted in the 1980s and early 1990s had documented a superiority over corticosteroids alone in terms of biochemical response (declines in serum prostate-specific antigen levels) and quality of life, but not survival. Due to their impact on pain control, mitoxantrone and prednisone were long considered the best regimen for symptomatic HRPC patients. In recent years, more chemotherapeutic agents have been tested, among which the microtubule inhibitors (vinca alkaloids and taxanes) have obtained the most promising results in Phase II trials and have entered Phase III testing. Two well-designed randomized trials have changed this scenario. Both compared docetaxel (with or without estramustine) against mitoxantrone and prednisone, and demonstrated a significant advantage not only in terms of response, pain control and quality of life, but also in terms of overall survival. Which patients need to be treated, the regimen of choice and duration of chemotherapy will be the next questions to be answered in the coming years in the field of HRPC, along with the role of new signal transduction inhibitors and other targeted therapies.


How mild traumatic brain injury may affect declarative memory performance in the post-acute stage.
Memory deficits are among the most frequently reported sequelae of mild traumatic brain injury (MTBI), especially early after injury. To date, these cognitive deficits remain poorly understood, as in most patients the brain is macroscopically intact. To identify the mechanism by which MTBI causes declarative memory impairments, we probed the functionality of the medial temporal lobe (MTL) and the prefrontal cortex (PFC), within 6 weeks after injury in 43 patients from a consecutive cohort, and matched healthy controls. In addition to neuropsychological measures of declarative memory and other cognitive domains, all subjects underwent functional magnetic resonance imaging (fMRI). Behavioral results showed poorer declarative memory performance in patients than controls, and decreasing performance with increasing duration of post-traumatic amnesia (a measure of injury severity). Task performance in the scanner was, as intended by the task and design, similar in patients and controls, and did not relate to injury severity. The task used reliably activated the MTL and PFC. Although we did not find significant differences in brain activity when comparing patients and controls, we revealed, in agreement with our neuropsychological findings, an inverse correlation between MTL activity and injury severity. In contrast, no difference in prefrontal activation was found between patients and controls, nor was there a relation with injury severity. On a behavioral level, injury severity was inversely related to declarative memory performance. In all, these findings suggest that reduced medial temporal functionality may contribute to poorer declarative memory performance in the post-acute stage of MTBI, especially in patients with longer post-traumatic amnesia.


Efficacy of Zinc Sulfate in Peptic Ulcer Disease: A Randomized Double-Blind Clinical Trial Study.
Peptic ulcer is a common disease that affects millions of people worldwide. Considering its global prevalence finding new approach for treating is important. The aim of this study was to investigate the effect of zinc sulfate on gastric and duodenal ulcer treatment. This double-blind clinical trial study was done on 90 patients who were admitted to the gastrointestinal endoscopy clinic of Tohid hospital in Sanandaj, Iran. All patients were diagnosed with gastric and duodenal ulcers. They were randomly divided into two-intervention and control groups, using block randomization with block sizes of 4. Patients and researcher were unaware of the grouping. To assess the level of zinc, blood samples were taken. In case of positive Rapid Urease Test (RUT), triple therapy regimen including amoxicillin, clarithromycin and omeprazole was administered for two weeks. For intervention group in addition to "triple therapy", an oral dose of Zinc Sulfate 220mg capsules were administered daily, while the control group received placebo capsules. A total of 54.5% and 57% of the patients in the intervention and control groups had gastric ulcer respectively. The Rapid Urease Test (RUT) result of 72.7% of intervention group and 83.3% of control group was positive (p = 0.24). Serum zinc level of 20.9% of intervention group and 35.7% of control group was lower than the normal level (p = 0.13). The mean of serum zinc level of intervention group and control group were 81.9 and 78.9 mg dL respectively (p = 0.4). After intervention, peptic ulcer in 81.8% of the intervention group and 83.3% of the control groups were improved (p= 0.85). Response to treatment were higher in patients with normal zinc levels compared to patients with abnormal levels (77.5% vs. 22.5%, p=0.019). A daily dose of 220mg zinc sulfate was not significantly effective on peptic ulcer. However, patients with normal zinc levels had better ulcer treatment.


Transplantation of the parathyroid glands in man: clinical indications and results.
The physiologic function of human parathyroid autografts and allografts has not been demonstrated conclusively. During the past 30 months, we have transplanted parathyroid glands in 29 patients and tested their functional status. One immunosuppressed aparathyroid patient received a parathyroid allograft from a parent who previously had been his renal transplant donor. Twenty-seven patients with renal failure and secondary hyperparathyroidism received parathyroid autografts immediately after total parathyroidectomy, and one patient received a parathyroid autograft at the time of total parathyroidectomy for primary chief cell hyperplasia. At transplantation 1 times 1 mm. parathyroid pieces were grafted into the forearm musculature. Of 11 transplanted patients (one allograft and ten autografts) followed for 1 year, ten are normocalcemic; only two (autografted patients) are on supplemental calcium. Ten of the 29 patients have had biopsies performed, and all have had intact parathyroid architecture and intracellular secretory granules demonstrated by light and electron microscopy. Parathyroid hormone content in the grafted tissue of five patients was 179 plus or minus 118.8 ng. per milligram. In 11 random patients in whom bilateral measurements have been made, the parathyroid hormone content in the antecubital vein blood draining the grafted tissue has been markedly higher than that in the simultaneously sampled antecubital vein blood of the nongrafted arm. These data demonstrate that parathyroid autografts or allografts secret hormone and maintain a normal serum calcium in the host.


The impact of pre-operative serum creatinine on short-term outcomes after liver resection.
The aim of the present study was to determine whether raised pre-operative serum creatinine increased the risk of renal failure after liver resection. Data were studied from 1535 consecutive liver resections. Outcomes in patients with pre-operative creatinine </=124 micromol/l (Group 1) were compared with those with pre-operative creatinine >/=125 micromol/l (Group 2). The median age of the 1446 (94.3%) patients resected in Group 1 was 62 years compared with 67 years in the 88 (5.7%) patients in Group 2 (P < 0.0001). Similarly this latter group had double the number of patients who were American Society of Anesthesiologists (ASA) III or IV (34.1% vs. 15.2%, P= 0.00004). Overall, the incidence of post-operative renal failure requiring haemofiltration was low (0.9%) but significantly more in Group 2 patients (5.7% vs. 0.6, P= 0.0007). In addition, patients in Group 2 were more likely to suffer acute kidney injury post-operatively (18.2% vs. 4.3%, P < 0.0001). Patients with acute kidney injury had significantly higher blood loss. Although there was no difference in mortality, patients in Group 2 had higher post-operative morbidity (37.5%) than Group 1 (21.7%, P= 0.0006), with the incidence of cardiorespiratory complications being higher in Group 2 (25.9% vs. 8.9%, P= 0.0025). After liver resection, renal failure is rare but patients with an elevated creatinine pre-operatively are at an increased risk of both renal and non-renal complications.


The world of twins: an update.
In last years, owing to the widespread availability of assisted-reproduction technology, multiple pregnancy rates in Western countries have increased. In twin pregnancies, an increased rate of gestational complications, intrauterine growth restriction (IUGR), preterm birth and severe perinatal conditions is present. These complications are more frequent in monozygotic twins compared to dizygotic twins as well as an increased relative risk of chromosomal abnormalities and congenital malformation. Monochorionic twins are at higher risk for complications, since they share a common placenta where an imbalance in unidirectional arteriovenous anastomoses can lead to twin–twin transfusion syndrome. This extremely dangerous condition, if not early identified, can determine severe fetal complications with mortality rates that, in case of no treatment, reaches 90%. Laser photocoagulation is the treatment of choice in severe twin-to-twin transfusion syndrome with high survival rate. IUGR occurs more frequently in MC twins and along with prematurity and perinatal pathology is considered an important determinant of developmental delay.


Metabolism of benzo(a)pyrene and 1-naphthol in cultured human tumorous and nontumorous colon.
The oxidative metabolism of benzo(a)pyrene and the conjugative metabolism of 1-naphthol by explant cultures of normal human colon and colonic tumor tissue, obtained at surgery, have been studied. After 24 hr in culture, the explants were exposed to either [1-14C]-1-naphthol (20 to 100 microM) or [3H]-benzo(a) pyrene (1.5 microM) for a further 1.5 to 24 hr. Both normal-appearing tissue and tumor tissue metabolized benzo(a)pyrene to a wide variety of organic solvent-soluble metabolites, including monohydroxybenzo(a)pyrenes, dihydrodiols, and tetrols. 1-Naphthol was metabolized by cultured human colonic mucosa and tumor tissue to both its glucuronic acid and sulfate ester conjugates. In the normal tissues, with naphthol (20 microM), sulfate ester conjugation predominated. However, with the tumor tissue, sulfate ester conjugation decreased; thus, the percentage of glucuronic acid conjugates, expressed as a percentage of total metabolites formed, was increased significantly compared to normal tissue. The relationship, if any, of these changes to neoplastic transformation is unclear. The technique of explant culture described in this study may be of use for the study of other facets of the pathobiology of solid tumors.


Multicentre, randomised, blinded, control trial of drug-eluting balloon vs Sham in recurrent native dialysis fistula stenoses.
Endovascular treatment of autogenous arteriovenous haemodialysis fistula stenosis has high reintervention rates. We investigate the effect of drug-eluting balloons in the treatment of recurrent haemodialysis fistula stenosis. This is a randomised, controlled, investigator-initiated and run, prospective, blinded, multicentre trial. Patients with recurrent autogenous arteriovenous haemodialysis fistula stenosis received standard endovascular treatment plus drug-eluting balloon or standard endovascular treatment plus uncoated balloon (Sham). Primary endpoint was late lumen loss in trial area on ultrasound at 6 weeks, 3, 6 and 12 months. Secondary endpoints were freedom from reintervention to the Index Trial Area and decline in fistula flow (Qa). Interim analysis was performed at 6 months (unblinded due to timeliness). Patients with 132 recurrent stenoses (48% in bare Nitinol stents) were randomised with 70 receiving drug-eluting balloon and 62 Sham. At 6 months, decline in late lumen loss was 0.23 ± 0.03 mm/month for Sham and 0.045 ± 0.03 mm/month for drug-eluting balloon arm, a significant difference (0.18 mm, p = 0.0002). At 12 months, this difference persisted at 0.12 mm (p = 0.0003). At 6 months, significant difference in late lumen loss for instent restenoses (p = 0.0004) was observed, with non-significant difference for unstented restenoses (p = 0.065). Mean time for freedom from reintervention was 10.14 months for Sham versus 42.39 months for drug-eluting balloon (p = 0.001). The same was shown for instent (p = 0.014) and unstented (p = 0.029) restenoses. Qa decline rate at 6 months was 36.89 mL/min/month (Sham) and 0.41 mL/min (drug-eluting balloon). The difference was significant (36.48 mL/min; p = 0.02) and persisted to 12 months (p = 0.44). Paclitaxel drug-eluting balloon significantly delays restenosis after angioplasty for recurrent autogenous arteriovenous haemodialysis fistula stenosis, persisting to 12 months. Drug-eluting balloon significantly increases freedom from reintervention at 12 months with these effects true in stented and unstented fistulas.


Mycobacterium tusciae sp. nov.
A new, slow-growing, scotochromogenic mycobacterium was isolated from a lymph node of an immunocompromised child and subsequently from tap water and from a respiratory specimen of a patient with chronic fibrosis. Alcohol-acid-fastness, lipid patterns and the G + C content clearly support the placement of this organism in the genus Mycobacterium. The isolates grew very slowly at temperatures ranging from 25 to 32 degrees C and showed activities of nitrate reductase, catalase, urease, arylsulfatase and Tween 80 hydrolysis. The organism was susceptible to all antimycobacterial drugs tested. The 16S rDNA sequence was unique and phylogenetic analysis placed the organism close to fast-growing species such as Mycobacterium farcinogenes, Mycobacterium komossense and Mycobacterium aichiense. These data support the conclusion that the isolates represent a new mycobacterial species, for which the name Mycobacterium tusciae sp. nov. is proposed. The type strain is strain FI-25796T; a culture of this strain has been deposited in the DSMZ as strain DSM 44338T.


Antiatherogenic properties of flavonoids: implications for cardiovascular health.
Epidemiological studies suggest that higher flavonoid intake from fruits and vegetables is associated with decreased risk for the development of cardiovascular disease. The mechanisms explaining this observation remain unclear, but current evidence suggests that flavonoids may exert their effects through the improvement of cardiovascular risk factors. The present review summarizes data suggesting that flavonoids improve endothelial function. inhibit low-density lipoprotein oxidation, decrease blood pressure and improve dyslipidemia. A large number of studies have reported the impact of consuming flavonoid-rich foods on biomarkers of cardiovascular disease risk in healthy volunteers or at-risk individuals. Most studies have focused on cocoa, soy, and green and black tea. Recent evidence suggests that some polyphenols in their purified form, including resveratrol, berberine and naringenin, have beneficial effects on dyslipidemia in humans and/or animal models. In a mouse model of cardiovascular disease, naringenin treatment, through correction of dyslipidemia, hyperinsulinemia and obesity, attenuated atherosclerosis. Therefore, the beneficial effects of flavonoids on multiple risk factors may explain, in part, the observed beneficial effects of flavonoids on cardiovascular disease.


Radiomics for Identification and Prediction in Metastatic Prostate Cancer: A Review of Studies.
Metastatic Prostate Cancer (mPCa) is associated with a poor patient prognosis. mPCa spreads throughout the body, often to bones, with spatial and temporal variations that make the clinical management of the disease difficult. The evolution of the disease leads to spatial heterogeneity that is extremely difficult to characterise with solid biopsies. Imaging provides the opportunity to quantify disease spread. Advanced image analytics methods, including radiomics, offer the opportunity to characterise heterogeneity beyond what can be achieved with simple assessment. Radiomics analysis has the potential to yield useful quantitative imaging biomarkers that can improve the early detection of mPCa, predict disease progression, assess response, and potentially inform the choice of treatment procedures. Traditional radiomics analysis involves modelling with hand-crafted features designed using significant domain knowledge. On the other hand, artificial intelligence techniques such as deep learning can facilitate end-to-end automated feature extraction and model generation with minimal human intervention. Radiomics models have the potential to become vital pieces in the oncology workflow, however, the current limitations of the field, such as limited reproducibility, are impeding their translation into clinical practice. This review provides an overview of the radiomics methodology, detailing critical aspects affecting the reproducibility of features, and providing examples of how artificial intelligence techniques can be incorporated into the workflow. The current landscape of publications utilising radiomics methods in the assessment and treatment of mPCa are surveyed and reviewed. Associated studies have incorporated information from multiple imaging modalities, including bone scintigraphy, CT, PET with varying tracers, multiparametric MRI together with clinical covariates, spanning the prediction of progression through to overall survival in varying cohorts. The methodological quality of each study is quantified using the radiomics quality score. Multiple deficits were identified, with the lack of prospective design and external validation highlighted as major impediments to clinical translation. These results inform some recommendations for future directions of the field.


Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length.
Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72-0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63-2.24; p(trend) = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.


Characterization of proteases and protease inhibitors in the rat stomach.
Previously our laboratory reported increased activity of the thiol proteinase cathepsin B in gastric juice after ethanol-induced mucosal injury. In this study we measured proteinase activity (PA) and proteinase inhibitory activity (PIA) with the general substrates hemoglobin, azocasein, and bovine serum albumin (BSA) at optimal pH (2.0, 5.6, and 7.4) of aspartic, cysteine, and serine proteinases. Homogenates of glandular stomach mucosa and gastric juice from fasted rats were incubated in the presence or absence of specific inhibitors and sulfhydryl (SH) alkylators N-ethylmaleimide and iodoacetate. PIA was measured after acid and heat inactivation of endogenous proteinases and addition of 20 micrograms/ml pepsin, 20 or 100 micrograms/ml thiol proteinase papain, or 20 micrograms/ml trypsin for 5 min before digestion at 37 degrees C. The highest proteolytic activity was found at pH 2.0 (pepsin) in juice and mucosal homogenate, but proteases were also found at pH 5.6 and 7.4, where pepsin was inactive. Pepstatin inhibited most proteolytic activity at pH 2.0. The SH protease inhibitor leupeptin diminished PA mainly at pH 5.6. N-ethylmaleimide or iodoacetate substantially reduced the PA in acidic milieu, with maximum effect at pH 5.6. Endogenous PIA, expressed as inhibition of the effect of 1 microgram of pepsin, papain, and trypsin on BSA, was 13.1, 1.4, and 9.2% in gastric mucosa and 15.3, 22.5, and 6.2% in gastric juice at pH 2.0, 5.6, and 7.4, respectively. We have concluded that 1) endogenous proteinases and inhibitors in rat stomach can be measured using BSA and hemoglobin as substrates, 2) of the proteinases found in the stomach, 98% was pepsin at pH 2.0 and up to 27% or 17% was SH sensitive at pH 5.6 or 7.4, respectively, and 3) proteinases and their specific endogenous inhibitors may play a role in gastric mucosal injury and protection.


Detailed polyphenolic profiling of Annurca apple (M. pumila Miller cv Annurca) by a combination of RP-UHPLC and HILIC, both hyphenated to IT-TOF mass spectrometry.
Annurca apple, a Southern Italian cultivar, possesses not only a particular taste and flavor, different from other types of apple, but also several healthy properties. With the aim to thoroughly elucidate the polyphenolic profile of this variety, listed as Protected Geographical Indication product, an extensive qualitative profiling of Annurca apple polyphenolic peel extract was carried out, by employing a combination of ultra high performance reversed phase (RP-UHPLC) and hydrophilic liquid chromatography (HILIC) coupled to ion trap-time of flight (IT-TOF) mass spectrometry. A total of 63 compounds were tentatively identified, 25 of which not reported in Annurca apple extract so far. Furthermore, thanks to the different selectivity obtained with the HILIC, in combination with accurate mass measurements, an improved separation and detection of procyanidins, was obtained. Moreover, the obtained profiles were compared with those of a conventional variety, such as Red Delicious (RD), highlighting their differences. This work contributes to increase the knowledge about the polyphenolic fingerprint of this typical apple variety.


Disparities by ethnicity, language, and immigrant status in occupational health experiences among Las Vegas hotel room cleaners.
We examined disparities in workers' occupational health experiences. We surveyed 941 unionized Las Vegas hotel room cleaners about their experiences with work-related pain and with employers, physicians, and workers' compensation. Data were analyzed for all workers and by ethnicity, language, and immigrant status. Hispanic and English as second language (ESL) workers were more likely than their counterparts to report work-related pain and, along with immigrant workers, to miss work because of this pain. Hispanic, ESL, and immigrant workers were not consistently at a disadvantage with regard to their own responses to work-related pain but were so with respect to reported responses by workers' compensation, physicians, and employers. There are indications of disparities in occupational health experiences within this job title. The use of different group classifications, while implying different mechanisms, produced similar results.


Mothers of Children Diagnosed with ADHD: A Descriptive Study of Maternal Experience during the First Three Years of Treatment.
Background: Attention deficit hyperactivity disorder is the most common childhood psychiatric disorder. Current treatment strategies do not provide a convincing improvement on overall functioning, and further, reciprocity between ADHD and attachment has been suggested. This suggests that we do not fully comprehend the mechanisms of the disorder. This study was part of a larger project investigating factors of potential importance when a child is diagnosed with ADHD. Aim: In this current study we aimed to gain a clearer understanding about whether the mothers experienced the diagnostic process and treatment as helpful. Method: Sixty children newly diagnosed with ADHD and their mothers were included three years prior to this study. Fifty-two (87%) completed a survey about their experience with the diagnostic process and the years after in the psychiatric system and the secondary healthcare sector. Forty-three had also participated in an attachment interview in the original study and answered questions about this. Discussion: The follow-up questionnaire was based on conversations with the mothers was not meant to be used as a quantitative measure. However, one point to take is that the mothers did often not feel the help offered to be sufficient. In our opinion, this underlines that we are still far from understanding what ADHD is and what causes the differences in developmental trajectories as well as how differences in etiological factors may call for more customized approaches in treatment strategies.


Awareness and use of insecticide treated nets among women attending ante-natal clinic in a northern state of Nigeria.
To determine the awareness, accessibility and use of ITN by pregnant women attending ante-natal clinic (ANC) at the Primary Health Care (PHC) level considering the Government commitment of ensuring that at least 60% of pregnant women benefit from ITN by year 2010. This descriptive cross sectional study was carried out in all 78 PHC centres in the state. Four hundred and fifty-five (455) pregnant women that consented to the study where interviewed during their ANC sessions using semi-structured questionnaires. Data entry and analysis was done on a micro computer; frequency tables and cross tabulations of important variables were done; and Chi-square test was used for the test of significance. About one-third 164 (36%) of the respondents were aware of ITN in malaria prevention, but less than a third 124 (27%) had ever used it and only 88 (19%) were currently using it, while 104 (23%) of the total respondents had a member of their household using ITN. Some of the difficulties encountered or experienced by respondents currently using ITN were scarcity of new nets, difficulty in getting chemicals for re-treatment of nets, non availability of quality ITN for sale. Three hundred and thirty-one (73%) respondents have never used ITN before because of lack of awareness 136 (41%), price of ITN is too costly 26 (8%) and non-availability of ITN for purchase 67 (20%). Respondents' age, educational level, parity and source of information or awareness on ITN have no significant influence on ITN use (P > 0.05); however, the frequency of malaria attack among respondents using ITN was lower than those not using it and this was significant (P > 0.0043). Awareness and utilization of ITN among pregnant women and their household members is still low despite Government policy of free ITN for vulnerable groups and subsidized nets for other people. There is need to focus on creating demand for ITNs through all available health information channels including social marketing.


Postvoid residual urine in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: pooled analysis of eleven controlled studies with alfuzosin.
A pooled analysis was conducted in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia to examine the relationship between the postvoid residual urine (PVR) volume and various clinical characteristics and to assess the effect of alfuzosin, a clinically uroselective alpha(1)-blocker, on PVR volume and any other associated outcome. Nine hundred fifty-three patients, 42 to 89 years old, with a baseline PVR volume between 50 and 350 mL (mean 106 mL) were enrolled in 11 double-blind controlled studies and received either alfuzosin (n = 607) or placebo (n = 346) for 1 to 6 months. The relationships between the baseline PVR volume measured by transabdominal ultrasound and age, symptoms, maximum flow rate (Qmax), estimated bladder capacity, and prostate-specific antigen level were assessed. The changes in the PVR volume with treatment were evaluated in all available patients at three endpoints (1, 3, and 6 months). At baseline, a PVR volume of 100 mL or greater was observed in 60%, 47%, and 39% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P = 0.001). The bladder capacity was also significantly related to the Qmax (P = 0.0001). No relationship was found between PVR volume and age, symptoms, or prostate-specific antigen level. The changes in the PVR volume with treatment were related to the baseline PVR volume. However, at all endpoints and whatever the baseline PVR volume, the decreases in the PVR volume were significantly (P <0.01) greater with alfuzosin than with placebo. Acute urinary retention occurred in 7 patients (2 [0.3%] of 607 patients taking alfuzosin and 5 [1.4%] of 346 patients taking placebo); 6 of these 7 patients had a baseline PVR volume greater than 100 mL. In this population of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, the PVR olume and bladder capacity were related to the baseline Qmax. Alfuzosin significantly reduced the PVR volume compared with placebo, and this effect was more marked in patients with a high PVR volume at baseline. Acute urinary retention occurred mainly in patients with a PVR volume greater than 100 mL and was less frequent in patients taking alfuzosin than in those taking placebo.


Stability of fully asynchronous discrete-time discrete-state dynamic networks.
We consider networks of a large number of neurons (or units, processors, ...), whose dynamics are fully asynchronous with overlapping updating. We suppose that the neurons take a finite number of states (discrete states), and that the updating scheme is discrete in time. We make no hypotheses on the activation function of the neurons; the networks may have multiple cycles and basins. We derive conditions on the initialization of the networks, which ensures convergence to fixed points only. Application to a fully asynchronous Hopfield neural network allows us to validate our study.


Preparation and characterization of co-amorphous Ritonavir-Indomethacin systems by solvent evaporation technique: improved dissolution behavior and physical stability without evidence of intermolecular interactions.
The aim of this study was to stabilize the amorphous form of Ritonavir (RTV) a BCS class-II drug with known amorphous stabilizing small molecule Indomethacin (IND) by co-amorphous technology. The co-amorphous samples were prepared by solvent evaporation technique in the molar ratios RTV:IND (2:1), RTV:IND (1:1), RTV:IND (1:2) and their amorphous nature was confirmed by XRPD, DSC and FT-IR. Physical stability studies were carried out at temp 25°C and 40°C for maximum up to 90 days under dry conditions. Solubility and dissolution testing were carried out to investigate the dissolution advantage of prepared co-amorphous systems. The amorphous mixtures of all tested molar ratios were found to become amorphous after solvent evaporation. The same was confirmed by detecting halo pattern in diffractograms of co-amorphous mixtures. The Tg values of all three systems were found to be more than 40°C, the highest being 51.88°C for RTV:IND (2:1) system. Theoretical Tg values were calculated by Gordon-Taylor equation. Insignificant deviation of theoretical Tg values from that of practical one, corroborated by FT-IR studies showed no evidence of intermolecular interactions between RTV and IND. Almost 3-folds increase in the solubility for both amorphous RTV and IND was found as compared to their respective crystalline counterparts. The study demonstrated significant increase in the dissolution rate as well as increase in the total amount of drug dissolved for amorphous RTV, however it failed to demonstrate any significant improvement in the dissolution behavior of IND.


Automated Detection of Epiretinal Membranes in OCT Images Using Deep Learning.
Development and validation of a deep learning algorithm to automatedly identify and locate ERM regions in OCT images. OCT images of 468 eyes were retrospectively collected from a total of 404 ERM patients. One expert manually annotated the ERM regions for all images. A total of 422 images (90%) and the rest 46 images (10%) were used as the training dataset and validation dataset for deep learning algorithm training and validation, respectively. One senior and one junior clinician read the images. The diagnostic results were compared. The algorithm accurately segmented and located the ERM regions in OCT images. The image-level accuracy was 95.65%, and the ERM region-level accuracy was 90.14%, respectively. In comparison experiments, the accuracies of the junior clinician improved from 85.00% and 61.29% without the assistance of the algorithm to 100.00% and 90.32% with the assistance of the algorithm. The corresponding results of the senior clinician were 96.15%, 95.00% without the assistance of the algorithm, and 96.15%, 97.50% with the assistance of the algorithm. The developed deep learning algorithm can accurately segmenting ERM regions in OCT images. This deep learning approach may help clinicians in clinical diagnosis with better accuracy and efficiency.


Prevalence and Incidence of Atrial Fibrillation in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: (Additive) Value of Implantable Loop Recorders.
Atrial fibrillation (AF) is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and has a negative impact on outcome. Reliable data on prevalence, incidence, and detection of AF from contemporary, prospective HFmrEF/HFpEF studies are scarce. This was a prespecified sub-analysis from a prospective, multicenter study. Patients with HFmrEF/HFpEF underwent 12-lead electrocardiography (ECG), 24 h Holter monitoring, and received an implantable loop recorder (ILR) at the study start. During the 2 year follow-up, rhythm monitoring was performed via ILR, yearly ECG, and two yearly 24 h Holter monitors. A total of 113 patients were included (mean age 73 ± 8 years, 75% HFpEF). At baseline, 70 patients (62%) had a diagnosis of AF: 21 paroxysmal, 18 persistent, and 31 permanent AF. At study start, 45 patients were in AF. Of the 43 patients without a history of AF, 19 developed incident AF during a median follow-up of 23 [15-25] months (44%; incidence rate 27.1 (95% confidence interval 16.3-42.4) per 100 person-years). Thus, after the 2-year follow-up, 89 patients (79%) had a diagnosis of AF. In 11/19 incident AF cases (i.e., 58%), AF was solely detected on the ILR. Yearly 12-lead ECG detected six incident AF cases and four of these cases were also detected on two yearly 24 h Holter monitors. Two incident AF cases were detected on an unplanned ECG/Holter. Atrial fibrillation is extremely common in heart failure with HFmrEF/HFpEF and may inform on symptom evaluation and treatment options. AF screening with an ILR had a much higher diagnostic yield than conventional modalities.


The elephant in the room: Inconsistency in scene viewing and representation.
We examined the extent to which semantic informativeness, consistency with expectations and perceptual salience contribute to object prioritization in scene viewing and representation. In scene viewing (Experiments 1-2), semantic guidance overshadowed perceptual guidance in determining fixation order, with the greatest prioritization for objects that were diagnostic of the scene's depicted event. Perceptual properties affected selection of consistent objects (regardless of their informativeness) but not of inconsistent objects. Semantic and perceptual properties also interacted in influencing foveal inspection, as inconsistent objects were fixated longer than low but not high salience diagnostic objects. While not studied in direct competition with each other (each studied in competition with diagnostic objects), we found that inconsistent objects were fixated earlier and for longer than consistent but marginally informative objects. In change detection (Experiment 3), perceptual guidance overshadowed semantic guidance, promoting detection of highly salient changes. A residual advantage for diagnosticity over inconsistency emerged only when selection prioritization could not be based on low-level features. Overall these findings show that semantic inconsistency is not prioritized within a scene when competing with other relevant information that is essential to scene understanding and respects observers' expectations. Moreover, they reveal that the relative dominance of semantic or perceptual properties during selection depends on ongoing task requirements. (PsycINFO Database Record


Zinc and copper nutriture in obese men receiving very low calorie diets of soy or collagen protein.
Balance studies for Zn and Cu were conducted over 40 days in 10 obese men housed in a metabolic balance unit. Two weight reduction diets providing 400 kcal and 100 g protein daily were administered; to five subjects, a collagen diet which was severely deficient in both Zn and Cu, and to another five subjects, a soy diet which provided a marginal intake of Zn and an adequate intake of Cu. Zn and Cu content of diets, plasma, red blood cells, urine, and feces were determined during eight 5-day periods. Balances were corrected for lean tissue catabolism or deposition. Holter ECG monitoring and measurement of the QTc interval were done on days 0 and 40. Both diets resulted in elevated plasma and red blood cell concentrations of Zn and Cu and in high urinary and fecal losses of Zn. By day 40, 6 of 10 subjects were in negative Zn balance. Urinary Zn was inversely correlated with measures of lean tissue catabolism. During each period, Cu balance was markedly positive in the soy-diet group and negative in the collagen-diet group. Shortening of prolonged QTc intervals was related to the Cu but not Zn status of the individual.


Categorical perception of sound frequency by crickets.
Partitioning continuously varying stimuli into categories is a fundamental problem of perception. One solution to this problem, categorical perception, is known primarily from human speech, but also occurs in other modalities and in some mammals and birds. Categorical perception was tested in crickets by using two paradigms of human psychophysics, labeling and habituation-dishabituation. The results show that crickets divide sound frequency categorically between attractive (<16 kilohertz) and repulsive (>16 kilohertz) sounds. There is sharp discrimination between these categories but no discrimination between different frequencies of ultrasound. This demonstration of categorical perception in an invertebrate suggests that categorical perception may be a basic and widespread feature of sensory systems, from humans to invertebrates.


Early endoscopic treatment of blunt traumatic pancreatic injury.
Blunt pancreatic trauma is a rare and challenging situation. In many cases, there are other associated injuries that mandate urgent operative treatment. Morbidity and mortality rates are high and complications after acute pancreatic resections are common. The diagnosis of pancreatic injuries can be difficult and often requires multimodal approach including Computed Tomography scans, Magnetic resonance imaging and Endoscopic retrograde cholangiopancreaticography (ERCP). The objective of this paper is to review the application of endoprothesis in the settings of pancreatic injury. A review of the English literature available was conducted and the experience of our centre described. While the classical recommended treatment of Grade III pancreatic injury (transection of the gland and the pancreatic duct in the body/tail) is surgical resection this approach carries high morbidity. ERCP was first reported as a diagnostic tool in the settings of pancreatic injury but has in recent years been used increasingly as a treatment option with promising results. This article reviews the literature on ERCP as treatment option for pancreatic injury and adds further to the limited number of cases reported that have been treated early after the trauma.


[Coexistence of Legionnaires' disease and Q fever in a single patient].
A case of Legionnaires' disease associated with Q fever is presented; this is probably the first reported case of concomitant infections with Legionella pneumophila and Coxiella burnetii. The pulmonary features of the illness were not typical of either disease. The difficulties of making a diagnosis in such cases are discussed.


Cost-utility analysis of taxane therapy.
A cost-utility analysis of docetaxel versus paclitaxel in patients with anthracycline-resistant metastatic breast cancer was reviewed. Cost-utility analysis provides estimates of the additional cost of a new therapy per quality-adjusted life-year (QALY) saved or gained. Utility scores measure the strength of a patient's preference for a given health state or outcome. Few studies have evaluated preferences in patients receiving cancer treatment. Since docetaxel may represent an advance in the management of anthracycline-resistant recurrent metastatic breast cancer, a decision-analysis model was developed to evaluate the pharmacoeconomics of this drug versus those of paclitaxel. Although the overall treatment costs of docetaxel were slightly higher than those of paclitaxel, docetaxel was associated with a gain of 0.0905 QALY per patient. This gain in QALYs is equivalent to 33 days of perfect health, which represents a substantial proportion of the life expectancy of one of these patients (typically no longer than nine months). The incremental cost-utility ratio associated with docetaxel therapy was estimated to be $4011 per QALY. Compared with paclitaxel, docetaxel for anthracycline-resistant metastatic breast cancer is within the acceptable range of cost-effectiveness ratios for most medical interventions. Cost-utility analysis is a valuable technique for evaluating new antineoplastic regimens that offer some treatment benefit but do not prolong survival compared with other therapeutic options.


Recurrent self-limited fungemia caused by Yarrowia lipolytica in a patient with acute myelogenous leukemia.
Yarrowia lipolytica is a weakly pathogenic yeast that is rarely isolated from the blood. We observed transient recurrent catheter-related fungemia attributable to this organism in a leukemic patient. The fungemia and accompanying fever subsided spontaneously. The data suggest that it might be possible to withhold specific treatment for Y. lipolytica fungemia even in an immunocompromised patient.


[New method for diagnosis of lipid metabolic disturbances].
A new analytical procedure for determining the fraction composition (FC) of lipoproteins (LP) is developed on the basis of the physical method small-angle X-ray scattering (SAXS). This method quantitatively determines the levels of the basic fractions of LP and their subfractions in plasma or serum to analyze LP FC and to diagnose lipid metabolic disturbances. The results obtained by this procedure were compared with those of gel-electrophoresis, biochemistry, and medical diagnosis. There was a good agreement of SAXS and routine methods. The new procedure shows extremely rapid (1.0-1.5 hr) analysis, uses a single reagent (such as the saccharose type), has a high accuracy, and resolution. The analysis requires as high as 0.05 ml of plasma or serum. LP FC may be analyzed both in protein-free and whole native plasma and sera. The findings may be used in clinical care for diagnosis of dyslipidemias and for researches.


Clinicopathological Characteristics of Ovarian Sclerosing Stromal Tumor with an Emphasis on TFE3 Overexpression.
A sclerosing stromal tumor is a very rare benign sex cord-stromal tumor of the ovary. Because its clinical presentation and imaging findings are similar to those of borderline or malignant epithelial tumors and other sex cord-stromal tumors, accurate preoperative clinical diagnosis can be difficult. The aim of this study was to analyze the clinicopathological characteristics of SSTs and examine the immunohistochemical expression TFE3, which has not been studied in SSTs. Our study cohort consisted of 9 patients diagnosed as having SST; the median age was 36 years. Radiologically, SSTs presented as multiseptated cystic masses, mixed echoic masses, pseudolobular masses, solid pelvic masses, or uterine subserosal nodules. In 4 of the 9 cases, the preoperative clinical impression was a borderline or malignant ovarian tumor. SSTs displayed the following histopathological features: 1) relatively well-circumscribed cellular nodules that were randomly distributed in the fibrous or edematous stroma; 2) a characteristic alternating pattern of hypercellular and hypocellular areas; 3) a hemangiopericytoma-like vascular growth pattern in the cellular nodules; 4) bland-looking spindle-shaped cells and round or polygonal cells densely clustered around blood vessels; and 5) red blood cell-containing intracytoplasmic vacuole-like spaces in the tumor cell cytoplasm, possibly indicating epithelioid hemangioendothelioma. Immunohistochemically, the tumor cells exhibited diffuse and moderate-to-strong TFE3 expression in 7 of the 9 SSTs. TFE3 was strongly expressed in the nuclei of round or polygonal cells and lutein cells. In contrast, neither luteinized thecomas nor fibromas appreciably expressed TFE3. In summary, our study describes characteristic histopathological features that may be useful for differentiating SSTs from other sex-cord stromal tumors and demonstrates for the first time that SSTs show strong TFE3 expression. Further investigations are necessary to clarify the role of TFE3 in the development of SSTs.


HIV-1 Nef protein expression in human CD34+ progenitors impairs the differentiation of an early T/NK cell precursor.
HIV-1 impairs the production of T cells, through mechanisms that are still unknown. Here, we investigated the effect of the expression of HIV-1 Nef on the T-cell potential of human hematopoietic CD34(+) precursors. Those progenitors were transduced by using lentiviral vectors expressing Nef and cultured on OP9-DL1 cells allowing the differentiation of T cell from human hematopoietic precursors. We demonstrate that Nef impairs the generation of a CD3epsilon(+)CD5(+) CD1a(+) precursor stage that has initiated a D-J rearrangement of the TCRbeta locus. Onward stages of T-cell development were also affected with a quantitative reduction of CD4(+) intraCD3epsilon(+) Immature single positive cells (ISP), Double Positive (DP) CD4(+)CD8(+) TCRalphabeta T cells and CD56(+) NK cells. But B cell production was not affected. Limiting dilution analyses demonstrated a significant reduction in the frequency of T/NK progenitors among Nef-expressing CD34(+) cells. Altogether, these data demonstrate that Nef interferes with the differentiation of a primitive lymphoid human precursor with a T/NK potential.


Perception of auditory signals.
Auditory signals are decomposed into discrete frequency elements early in the transduction process, yet somehow these signals are recombined into the rich acoustic percepts that we readily identify and are familiar with. The cerebral cortex is necessary for the perception of these signals, and studies from several laboratories over the past decade have made significant advances in our understanding of the neuronal mechanisms underlying auditory perception. This review will concentrate on recent studies in the macaque monkey that indicate that the activity of populations of neurons better accounts for the perceptual abilities compared to the activity of single neurons. The best examples address whether the acoustic space is represented along the "where" pathway in the caudal regions of auditory cortex. Our current understanding of how such population activity could also underlie the perception of the nonspatial features of acoustic stimuli is reviewed, as is how multisensory interactions can influence our auditory perception.


[A structural model for the practice of life safety behavior in school-age children].
This study is an examination of the paths in which the primary factors of anxiety, impulsiveness, knowledge of life safety practice, attitudes towards life safety practice, interpersonal support, and self-efficacy from Pender's Health Promotion Model influence the practice of life safety behavior in school-age children. The sample consisted of 489 5th and 6th grade students recruited from five elementary schools in Seoul City and four provinces, South Korea. Data were analyzed using descriptive statistics, correlations, factor analysis, and structural equation modeling. Attitudes towards life safety practice, interpersonal support, self-efficacy and impulsiveness directly influenced practice of life safety behavior. Anxiety did not have a direct influence on practice of life safety behavior, but indirectly affected it. In this modified model, 52.0% of the practice of life safety behavior was explained by the primary factors. To facilitate the practice life safety behaviors in late childhood, a positive attitude towards life safety needs to be developed along with decreasing impulsiveness and enhancing self-efficacy.


Postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance can link PPI-responsive heartburn to reflux better than acid exposure time.
Acid exposure time (AET) is considered the most useful parameter to predict response of reflux-related heartburn to medical or surgical treatment. However, recent studies showed high rates of heartburn response to proton pump inhibitor (PPI) therapy in patients with normal AET. We aimed to compare the efficacy of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) with AET in linking PPI-responsive heartburn to reflux. Off-therapy impedance-pH tracings from 425 patients, 317 with PPI-responsive and 108 with PPI-refractory heartburn were blindly re-analyzed. Demographic and endoscopic characteristics, conventional impedance-pH variables, PSPW index, and MNBI were assessed with multivariate logistic regression to identify factors independently associated with PPI responsiveness. Prediction models were developed to assess the strength of reflux linkage with factors independently associated with PPI responsiveness by calculating the area under the curve (AUC) at receiver-operating-characteristic (ROC) analysis. At multivariate logistic regression analysis, AET, MNBI, and PSPW index were the only factors independently associated with PPI responsiveness, abnormal values found in 60%, 76%, and 92% of PPI-responsive cases (P<.017). At ROC analysis, PSPW index (AUC:.794, P=.002) and MNBI (AUC: 0.742, P=.003), both separately and combined (AUC: 0.811, P<.001) linked reflux with PPI-responsiveness better than AET (AUC: 0.687). AET, PSPW index, and MNBI are independently associated with PPI-responsive heartburn. PSPW index and MNBI can link PPI-responsive heartburn to reflux better than AET and should become part of the standard analysis of impedance-pH tracings.