Sildenafil citrate improves self-esteem, confidence, and relationships in men with erectile dysfunction: Results from an international, multi-center, double-blind, placebo-controlled trial.
Erectile dysfunction (ED) can significantly impact a man's relationships and well-being. We assessed changes in self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction in men with ED using the validated Self-Esteem And Relationship questionnaire (SEAR). This was a 12-week, double-blind, placebo-controlled, flexible-dose (25, 50, 100 mg, as needed) international study of sildenafil in men > or =18 years of age in Mexico, Brazil, Australia, and Japan. The primary study outcome was change in self-esteem from baseline to the end of treatment. Secondary study measures were changes in other SEAR components, International Index of Erectile Function (IIEF) domains, percentage of intercourse attempts that were successful, and the response to a global efficacy question at the end of treatment. Patients were well balanced for age and duration of ED (placebo = 149 and sildenafil = 151). Compared with placebo, sildenafil significantly improved self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction (P < 0.0001). The psychosocial measures of well-being assessed with the SEAR were positively correlated (range 0.60-0.86, P < 0.0001) with erectile function, the frequency of achieving erections that allowed satisfactory sexual intercourse, the percentage of successful sexual intercourse attempts, and global treatment efficacy. Significant improvements in self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction after treatment of ED with sildenafil were consistent among countries. These data suggest a substantial cross-cultural improvement in well-being after successful treatment of ED with sildenafil.


Metastasis-associated protein 1 nuclear expression is closely associated with tumor progression and angiogenesis in patients with esophageal squamous cell cancer.
The purposes of the present study were to detect the expression of metastasis-associated protein 1 (MTA1) in patients with esophageal squamous cell cancer (ESCC), and to evaluate the relevance of MTA1 protein expression to the tumor progression, angiogenesis, and prognosis. Both MTA1 protein and intratumoral microvessels were examined by immunohistochemical staining in 131 ESCC patients who successfully underwent subtotal esophagectomy and esophagogastric anastomosis at Qilu Hospital between Jan 2004 and Dec 2005. Intratumoral microvessel density (MVD) was recorded by counting CD-34 positive immunostained endothelial cells. All statistical analyses were performed with SPSS 13.0 statistical software. High expression of MTA1 protein was detected in 57 cases and significantly correlated with tumor invasion depth (P = 0.041), lymph node metastasis (P = 0.021), pathologic stage (P = 0.003), and MVD (P = 0.044). Survival analysis showed that patients with MTA1 protein high expression had significantly poor overall 5-year survival (P = 0.002), and the factor found on multivariate analysis to significantly affect overall survival was only pathologic stage (P = 0.040). Further stratified survival analysis split by pathologic stage demonstrated that MTA1 protein high expression significantly predicted unfavorable prognosis among patients with pathologic stage II disease (P = 0.006). High expression of the MTA1 protein is common in ESCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. These findings indicate that MTA1 protein has clinical potentials as a useful indicator of progressive phenotype, a promising prognostic predictor to identify patients with poor prognosis, and a potential novel therapeutic target of antiangiogenesis for patients with ESCC.


Cobalamin-dependent methionine synthase from Escherichia coli B: electron paramagnetic resonance spectra of the inactive form and the active methylated form of the enzyme.
Cobalamin-dependent methionine synthase (5-methyltetrahydrofolate-homocysteine methyltransferase, EC 188.8.131.52) has been isolated from Escherichia coli B in homogeneous form. The enzyme is isolated in an inactive form with the visible absorbance properties of cob(II)alamin. The inactive enzyme exhibits an electron paramagnetic resonance (EPR) spectrum at 38 K that is characteristic of cob(II)alamin at acid pH, where the protonated dimethylbenzimidazole substituent is not coordinated with the cobalt nucleus (base-off cobalamin). An additional, variable component of the EPR spectrum of the inactive enzyme has the characteristics of a cob(III)alamin-superoxide complex. Previous work by others [Taylor, R.T., & Weissbach, H. (1969) Arch. Biochem. Biophys. 129, 745-766. Fujii, K., & Huennekens, F.M. (1979) in Biochemical Aspects of Nutrition (Yagi, K., Ed.) pp 173-183, Japan Scientific Societies, Tokyo] has demonstrated that the enzyme can be activated by reductive methylation using adenosylmethionine as the methyl donor. We present data indicating that the conversion of inactive to methylated enzyme is correlated with the disappearance of the EPR spectrum as expected for the conversion of paramagnetic cob(II)alamin to diamagnetic methylcobalamin. When the methyl group is transferred from the methylated enzyme to homocysteine under aerobic conditions, cob(II)alamin/cob(III)alamin-superoxide enzyme is regenerated as indicated by the return of the visible absorbance properties of the initially isolated enzyme and partial return of the EPR spectrum. Our enzyme preparations contain copper in approximately 1:1 stoichiometry with cobalt as determined by atomic absorption spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)


Elesesterpenes A-K: Lupane-type Triterpenoids From the Leaves of Eleutherococcus sessiliflorus.
Elesesterpenes A-K (1-11), eleven new lupane-type triterpenoids, triterpenoid glycosides, and nortriterpenoid were isolated from the leaves of Eleutherococcus sessiliflorus. Their structures and relative configurations were completely elucidated by a combination of diverse methods including physical, spectroscopic data. The absolute configuration of elesesterpenes A-B (1-2) was defined by single-crystal X-ray diffraction. Meanwhile, all the isolates were evaluated for anti-inflammatory activities on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells, and antiproliferative activities against human hepatoma (HepG2), human lung adenocarcinoma (A549), and human glioma cells (LN229) in vitro. It was found that some of them exhibited obvious anti-inflammatory activities and potent antiproliferative activities.


Decline in serum antibodies to methyltetrahydrophthalic anhydride after cessation of exposure.Implications for use as a biomarker.
T he association between exposure intensity and serum levels of immunoglobulins E and G against low molecular weight compounds was evaluated. The decay of levels of specific IgE and IgG antibodies was studied after cessation of exposure in workers exposed to the inhalant allergen methyltetrahydrophthalic anhydride in a plant using epoxy resins. Sera have been collected in workers for 18-84 (mean value 54) months after cessation of exposure. Specific IgE and IgG was assessed by RAST and ELISA, respectively. The mean of individual half-times for IgE (N = 10) and IgG (N = 8) was 0 9 (range 0 1-1 8) and 0 4 (range 0 2-0 6) years, respectively, after total avoidance of exposure. Corresponding decreases of IgE and IgG were also observed after reduction, but not total elimination, of exposure. No correlation was seen between biologic halftimes of specific IgE and total IgE, atopy, smoking habits or gender. The results indicate that the levels of specific antibodies in sensitized individuals reflect long term exposure, and may persist for years after the end of exposure.


Experiences of receiving a diagnosis of multiple sclerosis: a meta-synthesis of qualitative studies.
This meta-synthesis aimed to synthesise qualitative evidence on experiences of people with Multiple Sclerosis (MS) in receiving a diagnosis, to derive a conceptual understanding of adjustment to MS diagnosis. Five electronic databases were systematically searched to identify qualitative studies that explored views and experiences around MS diagnosis. Papers were quality-appraised using a standardised checklist. Data synthesis was guided by principles of meta-ethnography, a well-established interpretive method for synthesising qualitative evidence. Thirty-seven papers were selected (with 874 people with MS). Synthesis demonstrated that around the point of MS diagnosis people experienced considerable emotional upheaval (e.g., shock, denial, anger, fear) and difficulties (e.g., lengthy diagnosis process) that limited their ability to make sense of their diagnosis, leading to adjustment difficulties. However, support resources (e.g., support from clinicians) and adaptive coping strategies (e.g., acceptance) facilitated the adjustment process. Additionally, several unmet emotional and informational support needs (e.g., need for personalised information and tailored emotional support) were identified that, if addressed, could improve adjustment to diagnosis. Our synthesis highlights the need for providing person-centred support and advice at the time of diagnosis and presents a conceptual map of adjustment for designing interventions to improve adjustment following MS diagnosis.Implications for RehabilitationThe period surrounding Multiple Sclerosis diagnosis can be stressful and psychologically demanding.Challenges and disruptions at diagnosis can threaten sense of self, resulting in negative emotions.Adaptive coping skills and support resources could contribute to better adjustment following diagnosis.Support interventions should be tailored to the needs of newly diagnosed people.


Determination of threshold concentrations of allergens and evaluation of two different histamine concentrations in canine intradermal testing.
The purpose of this study was to determine the optimal histamine concentration and allergen threshold concentrations for canine intradermal testing. Thirty healthy dogs were tested using two different concentrations of histamine and four different concentrations of each allergen. The optimal histamine concentration was determined to be 1:10 000 w/v. The threshold concentration was at least 1750 PNU/mL for all tested grasses, weeds, trees, moulds and insects, except for fleas which was as least 1:500 w/v. For Dermatophagoides pteronyssinus, the optimal threshold concentration was 250 PNU/mL, whereas for Dermatophagoides farinae and Tyrophagus putrescentiae, it was 100 PNU/mL. Threshold concentration for all epidermals except human dander was at least 1250 PNU/mL. The optimal threshold concentration for human dander was 300 PNU/mL. Our results suggest that the currently used 1:100 000 w/v concentration of histamine and the 1000 PNU/mL concentration for most grasses, weeds, trees, moulds, epidermals and insects may not be appropriate for canine intradermal testing.


Ultrafast electrical measurements of polarization dynamics in ferroelectric thin-film capacitors.
We have developed a new approach to measure fast electrical signals during polarization switching in ferroelectric thin-film capacitors. This article describes a simple method for probing transient currents and voltages in a broad range of time scales from microseconds to hundreds of picoseconds. In order to test our approach, we probed polarization dynamics in commercial PbZr(0.2)Ti(0.8)O(3) ferroelectric capacitors in which the measured switching time was as fast as 1.7 ns.


Methyl pyruvate stimulates pancreatic beta-cells by a direct effect on KATP channels, and not as a mitochondrial substrate.
In pancreatic beta-cells, methyl pyruvate is a potent secretagogue and is widely used to study stimulus-secretion coupling. In contrast with pyruvate, which barely stimulates insulin secretion, methyl pyruvate was suggested to act as an effective mitochondrial substrate. We show that methyl pyruvate elicited electrical activity in the presence of 0.5 mM glucose, in contrast with pyruvate. Accordingly, methyl pyruvate increased the cytosolic free Ca(2+) concentration after an initial decrease, similar to glucose. The initial decrease was inhibited by thapsigargin, suggesting that methyl pyruvate stimulates ATP production. This assumption is supported by the observation that methyl pyruvate hyperpolarized the mitochondrial membrane potential, similar to glucose. However, in contrast with glucose, methyl pyruvate even slightly decreased NAD(P)H autofluorescence and did not influence ATP production or the ATP/ADP ratio. This observation questions the suggestion that methyl pyruvate acts as a powerful mitochondrial substrate. The finding that methyl pyruvate directly inhibited a cation current across the inner membrane of Jurkat T-lymphocyte mitochondria suggests that this metabolite may increase ATP production in beta-cells by activating the respiratory chains without providing reduction equivalents. We conclude that this mechanism may account for a slight and transient increase in ATP production. We further show that methyl pyruvate inhibited the K(ATP) current measured in the standard whole-cell configuration, an effect that was at least partly antagonized by diazoxide. Accordingly, single-channel currents in inside-out patches were blocked by methyl pyruvate. We conclude that inhibition of K(ATP) channels, and not activation of metabolism, mediates the induction of electrical activity in pancreatic beta-cells by methyl pyruvate.


Advanced glycation end products, oxidative stress and diabetic nephropathy.
About 246 million people worldwide have diabetes in 2007. The global figure of people with diabetes is projected to increase to 370 million in 2030. As the prevalence of diabetes has risen to epidemic proportions worldwide, diabetic nephropathy has become one of the most challenging health problems. Therapeutic options such as strict blood glucose and blood pressure controls are effective for preventing diabetic nephropathy, but are far from satisfactory, and the number of diabetic patients on end-stage renal disease is still increasing. Therefore, a novel therapeutic strategy that could halt the progression of diabetic nephropathy should be developed. There is accumulating evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate under diabetes, play a role in diabetic nephropathy via oxidative stress generation. In this paper, we review the pathophysiological role of AGEs and their receptor (RAGE)-oxidative stress system in diabetic nephropathy.


Dysfluency in Huntington's disease, Parkinson's disease and schizophrenia.
Verbal fluency was compared in Huntington's disease (n=12), Parkinson's disease (n=25) and schizophrenia (n=18) with a series of fluency tasks evaluating the effects on productivity of cuing with subordinate categories and alternation between fluency probes. Findings indicated reduced output in the patient groups across all tasks consistent with a difficulty in intrinsic generation. A significant group interaction was observed with cue provision, but not with alternation. The facilitation of performance with cuing in all groups suggests a common mechanism of disruption in these disorders, most likely reflecting interruption of the prefrontal modulation of retrieval processes. To explain the observed pattern, we propose that the semantic retrieval anomaly in these disorders reflects a difficulty in intrinsic extra-dimensional shift. Verbal productivity was significantly associated with negative dimensions of schizophrenia, such as poverty of speech and flattened affect, a finding that is discussed in terms of the neurocognitive heterogeneity of schizophrenia and theories of cognitive dysfunction in subtypes of this disorder.


Possible involvement of sigma-1 receptors in the anti-immobility action of bupropion, a dopamine reuptake inhibitor.
Sigma receptors particularly, sigma-1 subtype is known to modulate the release of catecholamines in the brain and may participate in the mechanism of action of various antidepressants. The present study investigated the possible involvement of sigma receptors in modulating the anti-immobility-like effect of bupropion (a dopamine reuptake inhibitor) using the forced swim test (FST) in mice. Bupropion produced dose-dependent (10-40 mg/kg, i.p.) reduction in immobility period and the ED(50) value was found to be 18.5 (7.34-46.6) mg/kg, i.p. (+)-Pentazocine (2.5 mg/kg, i.p.), a high-affinity sigma-1 receptor agonist, produced synergistic response when it was co-administered with a subeffective dose of bupropion (10 mg/kg, i.p.). On the contrary, pretreatment with progesterone (10 mg/kg, s.c.), a sigma-1 receptor antagonist neurosteroid, rimcazole (5 mg/kg, i.p.), another sigma-1 receptor antagonist, or BD 1047 (1 mg/kg, i.p.), a novel sigma-1 receptor antagonist, reversed the anti-immobility effects of bupropion (20 mg/kg, i.p.). The various modulators used in the study did not show any effect per se on locomotor activity except bupropion which at a higher dose (15-40 mg/kg, i.p.) significantly increased the locomotor activity. The results for the first time demonstrated the involvement of sigma-1 receptors in the anti-immobility effects of bupropion.


Hand-assisted laparoscopic surgery versus the open approach in curative resection of rectal cancer.
This prospective, randomized study compared the outcomes of hand-assisted laparoscopic surgery (HALS) with open surgery for the resection of rectal cancer. The main outcome measures were procedure time, blood loss, post-operative pain, time to oral intake, return of bowel function, length of hospital stay, morbidity and functional recovery. Patients in each group were similar with regard to general status, procedure types and the histopathological features of tumours. Procedure times were significantly longer with HALS versus open surgery. Analgesic requirements, surgical blood loss, time to first passing flatus, time to first oral fluids and post-operative hospital stay length were all significantly shorter in the HALS group. At a median follow-up of 16.3 months, local recurrence of tumour was not observed in either group. In this study, the HALS approach for curative resection of rectal cancer was safe and effective and may offer several potential advantages to patients in their post-operative recovery.


The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity.
The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity. Caffeine is detected by 5 of the 25 gustatory bitter taste receptors (hTAS2Rs) as well as by intestinal STC-1 cell lines. Thus there is a possibility that caffeine may elicit reflex autonomic responses via chemosensory stimulation. The cardiovascular impacts of double-espresso coffee, regular (130 mg caffeine) and decaffeinated, and encapsulated caffeine (134 mg) were compared with a placebo-control capsule. Measures of four post-ingestion phases were extracted from a continuous recording of cardiovascular parameters and contrasted with pre-ingestion measures. Participants (12 women) were seated in all but the last phase when they were standing. Both coffees increased heart rate immediately after ingestion by decreasing both the diastolic interval and ejection time. The increases in heart rate following the ingestion of regular coffee extended for 30 min. Encapsulated caffeine decreased arterial compliance and increased diastolic pressure when present in the gut and later in the standing posture. These divergent findings indicate that during ingestion the caffeine in coffee can elicit autonomic arousal via the chemosensory stimulation of the gustatory receptors which extends for at least 30 min. In contrast, encapsulated caffeine can stimulate gastrointestinal receptors and elicit vascular responses involving digestion. Research findings on caffeine are not directly applicable to coffee and vice versa. The increase of heart rate resulting from coffee drinking is a plausible pharmacological explanation for the observation that coffee increases risk for coronary heart disease in the hour after ingestion.


[Anti-K99 vaccination and colostric protection of calves infected experimentally with Escherichia coli K99].
Colostral antibodies of cows vaccinated with E. coli B41 (O101: K99, F41) protect completely B41 experimentally infected calves. In order to know more precisely the role of K99, F41 antibodies in protection, calves receiving the colostrum of B41 vaccinated cows are infected with E. coli B44 (O9: K30: H-K99, F41). Vaccination multiplies K99 antibodies in colostrum by seven. In B44 infected calves, specific K99, F41 antibodies protect only 3 out of 6 calves completely. Additive effect of antibodies against K99 and other surface antigens of enterotoxigenic E. coli seems desirable for a more complete protection.


Substituent effects in halogen bonding complexes between aromatic donors and acceptors: a comprehensive ab initio study.
Substituent effects in halogen bonding complexes involving aromatic rings are investigated. We have analyzed how the interaction energy (the RI-MP2/aug-cc-pVDZ level of theory) is affected by the substitution in both halogen bond donor and acceptor aromatic moieties. In addition, we have used two different aromatic electron donor molecules pyridine and cyanobenzene, which allow us to study the effect of having the electron donor nitrogen atom forming part of the ring or outside the ring (-CN). Interestingly, the effect of the substituents on the interaction energies is similar in both cases. We have obtained the Hammett's plots for four combinations of aromatic donors and acceptors and in all cases we have obtained good regression plots (interaction energies vs. Hammett's σ parameter). We have also studied and compared bifurcated halogen bonds using both possible combinations, that is two donors and one acceptor and vice versa. In addition, we have analyzed the effect of the solvent on the interaction energies using COSMO. Finally, we have used Bader's theory of "atoms-in-molecules" to demonstrate that the electron density computed at the bond critical point that emerges upon complexation can be used as a measure of bond order in this noncovalent interaction.


Child survivors of the Holocaust--strategies of adaptation.
Child survivors have only recently been recognized as a developmentally distinct group with psychological experiences different from older survivors. The wartime circumstances of Nazi persecution caused enforced separation from family and friends, and all the survivors experienced persecution in the form of physical and emotional abuse, starvation and degradation, and were witnesses to cruelty. This paper is based on information from interviews and therapy with 25 child survivors, the majority of whom were not patients. Coping strategies are discussed in terms of their survival value in wartime and post-war adaptive value. Three themes which reverberate throughout the lives of child survivors, now adults, are discussed in greater detail: bereavement, memory and intellect. The fact that the majority of child survivors live normal and creative lives provides an opportunity to learn what factors have served them over 40 years, to provide the resilience and strength to cope after such a shattering beginning.


Early intervention for people at high risk of developing bipolar disorder: a systematic review of clinical trials.
Early intervention approaches are built on the premise of preventing disability, burden, and cognitive sequelae caused by bipolar disorder. The objective of this systematic review was to characterise the effectiveness of all the available psychological and pharmacological treatments for early intervention in people at high risk of developing bipolar disorder. The study was registered with PROSPERO (CRD42019133420). We did a systematic search to identify studies published in ten databases up to March 27, 2020. Randomised controlled trials and cohort studies that assessed the effect of pharmacological or psychological interventions in people at high risk of developing bipolar disorder were included. Studies of first episodes of mania were excluded. Eligible papers were assessed for quality and data were extracted. The primary outcomes were change in manic and depressive symptoms from baseline to endpoint. Of the 2856 citations retrieved by our search, 16 studies were included; five evaluated pharmacotherapeutic strategies (three randomised controlled trials and two open-label studies), ten assessed psychotherapeutic strategies (four randomised controlled trials and six open-label studies), and one randomised controlled trial assessed combination therapy; these 16 trials included a total of 755 participants at high risk of developing bipolar disorder. Quality assessment indicated fair to good quality for open-label studies, and a high risk of bias in four randomised controlled trials. Among the pharmacotherapeutic interventions, there is preliminary support for the efficacy of aripiprazole in reducing mood symptoms in people at high risk of developing bipolar disorder. Psychological interventions were effective for various outcomes. There was substantial methodological heterogeneity across studies. This systematic review underscores the need for multicentre, prospective, methodologically homogeneous studies evaluating conversion to bipolar disorder as an outcome measure.


Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch micro-fabricated micro-needles.
Micro-needle arrays increase skin permeability by forming channels through the outer physical barrier, without stimulating pain receptors populating the underlying dermis. It was postulated that micro-needle arrays could facilitate transfer of DNA to human skin epidermis for cutaneous gene therapy applications. Platinum-coated "wet-etch" silicon micro-needles were shown to be of appropriate dimensions to create micro-conduits, approximately 50 microm in diameter, extending through the stratum corneum (SC) and viable epidermis. Following optimisation of skin explant culturing techniques and confirmation of tissue viability, the ability of the micro-needles to mediate gene expression was demonstrated using the beta-galactosidase reporter gene. Preliminary studies confirmed localised delivery, cellular internalisation and subsequent gene expression of pDNA following micro-needle disruption of skin. A combination of this innovative gene delivery platform and the ex vivo skin culture model will be further exploited to optimise cutaneous DNA delivery and address fundamental questions regarding gene expression in skin.


Cardiovascular reactivity to stress predicts future blood pressure status.
Cardiovascular reactivity to stress may have a pathophysiological role in neurogenic hypertension. We studied the value of measuring blood pressure change during standardized mental and physical challenges to prediction of resting blood pressure status 6.5 years later among 206 middle-aged adults and their 164 children, with the latter group originally being tested while enrolled in elementary through high school. After adjustment for age, resting blood pressure, and body mass index at study entry, as well as length of follow-up, larger systolic and diastolic blood pressure responses to a combination of mental and physical challenges were associated with higher subsequent resting diastolic blood pressure 6.5 years later among adults. Among boys, but not among girls, larger systolic and diastolic blood pressure responses to challenge were associated with higher subsequent resting blood pressure. These data suggest that people who are at high risk for elevated blood pressure might have an exaggerated stress-induced cardiovascular response at a younger age.


Sustainable Food Systems in Fruits and Vegetables Food Supply Chains.
Fruits and vegetables wastes (e.g., peel fractions, pulps, pomace, and seeds) represent ~16% of total food waste and contribute ~6% to global greenhouse gas emissions. The diversity of the fruit-horticultural production in several developing countries and the excess of certain fruits or vegetables in the months of greatest production offer unique opportunities for adding value to these wastes (co-products). Within the scope of the Circular Economy, valorization of such wastes for the production of innovative bio-ingredients can open great market opportunities if efficiently exploited. In this context, this review deals with the current situation of wastes arising from fruits and vegetables (availability, characterization) as sources of valuable ingredients (fiber, polyphenols, pigments) suitable to be incorporated into food, pharmaceutical and cosmeceutical products. In addition, an integral and systematic approach including the sustainable technologies generally used at both lab and industrial scale for efficient extraction of bioactive compounds from fruits and vegetables wastes are addressed. Overall, this review provides a general updated overview regarding the situation of fruits and vegetables chain supplies in the post-pandemic era, offering an integrative perspective that goes beyond the recovery of fiber and phytochemicals from the previous mentioned wastes and focuses on whole processes and in their social and economic impacts.


Anisotropic ionic conductivities in lyotropic supramolecular liquid crystals.
The designed aromatic amide discotic molecule with sulfonic acid groups at its periphery exhibits a hexagonal supramolecular columnar liquid crystalline phase, which leads to the achievement of anisotropic ionic conductivity through macroscopically aligning the ionic channels.


Changing Features of COVID-19: Characteristics of Infections with the SARS-CoV-2 Delta (B.1.617.2) and Alpha (B.1.1.7) Variants in Southern Italy.
Differences in the demographic and clinical characteristics of patients infected with the Alpha and Delta SARS-CoV-2 variants of concern in a large region of Southern Italy were assessed. Two cohorts of positive patients were compared. The Alpha group consisted of 11,135 subjects diagnosed between 21 March and 21 April 2021, and the Delta group consisted of 499 positive subjects diagnosed between 21 July and 21 August 2021. A descriptive and statistical analysis of the demographic and clinical characteristics of the two groups was performed. The proportion of patients with mild and moderate infections was significantly higher in the Delta than in the Alpha group (p < 0.001). In fully vaccinated patients, the proportion of symptomatic individuals was significantly higher in the Delta than in the Alpha group. The Delta group showed odds ratios of 3.08 (95% CI, 2.55-3.72) for symptomatic infection and 2.66 (95% CI, 1.76-3.94) for hospitalization. Improving COVID-19 vaccination rates is a priority, since infection with the SARS-CoV-2 Delta variant has a significant impact on patient outcomes. Additional targeted prevention strategies such as social distancing, the use of masks in indoor settings irrespective of vaccination status, and the use of a sanitary passport could be crucial to contain further spread of SARS-CoV-2 infection.


Overcoming the hurdles of tumor immunity by targeting regulatory pathways in innate and adaptive immune cells.
The improved understanding of the biochemical nature of tumor antigens and the identification of cellular and molecular mechanisms leading to activation of innate and adaptive immune cells have been of paramount importance in the progress of tumor immunology. Studies on the intricate network of interactions between tumor and immune cells have revealed novel regulatory signals, including cell surface inhibitory receptors and costimulatory molecules, intracellular regulatory pathways, immunosuppressive cytokines and proapoptotic mediators, which may operate in concert to orchestrate tumor-immune escape. This emerging portfolio of inhibitory checkpoints can influence the physiology of innate immune cells including dendritic cells, macrophages and natural killer (NK) cells, as well as different subsets of T cells to fine tune their effector function. The synergistic combination of strategies aimed at overcoming regulatory signals and/or stimulating effector pathways, may offer therapeutic advantage as adjuvants of conventional anticancer therapies. Based on this premise, we will discuss here how the control of the effector functions of innate and adaptive immune cells and the manipulation of regulatory pathways, either alone or in combination, could be exploited for therapeutic purposes in cancer patients.


The incidence of suicide in palliative care patients.
Anecdotal reports from hospices show a low incidence of suicide, yet depression is increased in cancer patients, and the likelihood of suicide is increased in depressed patients. Suicide would be expected to be more common in terminally ill patients. A postal survey was undertaken of 43 palliative care units. They were asked to report the number of suicides, parasuicides and the total number of referrals for the five-year period from 1990 to 1994. Thirty-four units replied (79%). Complete data were available from 24 (56%) units. Total referrals were 72,633 in the five-year period. Nine units (38%) had one or more suicides, with a total of 21 suicides reported. Sixteen units (67%) had one or more attempted suicides (total 37). There are implications in the study both for direct patient care, but also data collection, staff support and training.


Fabrication and Biocompatibility Evaluation of Nanodiamonds-Gelatin Electrospun Materials Designed for Prospective Tissue Regeneration Applications.
Due to the reduced ability of most harmed tissues to self-regenerate, new strategies are being developed in order to promote self-repair assisted or not by biomaterials, among these tissue engineering (TE). Human adipose-derived mesenchymal stem cells (hASCs) currently represent a promising tool for tissue reconstruction, due to their low immunogenicity, high differentiation potential to multiple cell types and easy harvesting. Gelatin is a natural biocompatible polymer used for regenerative applications, while nanodiamond particles (NDs) are used as reinforcing nanomaterial that might modulate cell behavior, namely cell adhesion, viability, and proliferation. The development of electrospun microfibers loaded with NDs is expected to allow nanomechanical sensing due to local modifications of both nanostructure and stiffness. Two aqueous suspensions with 0.5 and 1% w/v NDs in gelatin from cold water fish skin (FG) were used to generate electrospun meshes. Advanced morpho- and micro-structural characterization revealed homogeneous microfibers. Nanoindentation tests confirmed the reinforcing effect of NDs. Biocompatibility assays showed an increased viability and proliferation profile of hASCs in contact with FG_NDs, correlated with very low cytotoxic effects of the materials. Moreover, hASCs developed an elongated cytoskeleton, suggesting that NDs addition to FG materials encouraged cell adhesion. This study showed the FG_NDs fibrous scaffolds potential for advanced TE applications.


[Knowledge and attitude of clinical interns on pain management].
To investigate clinical interns' knowledge and attitude on pain management, influential factors and requirement. A total of 212 clinical interns were investigated by the self-designed general condition questionnaire and the Chinese version of the knowledge and attitude survey regarding pain (KASRP). The correct answer rate for the knowledge and attitude questionnaire was (51.70±14.18)%. The education background, the condition of pain education in clinical practice and the use of pain assessment tools were the key factors that impact the scores of knowledge and attitude on pain management. Clinical interns' perception on pain management is insufficient. It cannot meet the clinical actual needs. The medical colleges are lack of pain management education courses and standardization training. Schools and hospitals are encouraged to offer and strengthen pain education for clinical interns to create a good environment for pain treatment and to improve the management level for patients' quality of life.


Deep Convolutional Neural Networks for left ventricle segmentation.
Left ventricle (LV) segmentation is crucial for quantitative cardiac function analysis. Manual segmentation of the endocardium and epicardium is highly cumbersome; physicians limit delineation to the end-diastolic and end-systolic phases. A fully automated system could provide an analysis of cardiac morphology for all phases in a much shorter time. Most of the current LV segmentation methods are semi-automated and require error prone manual initialization. A fully-automated LV segmentation method would expedite the functional analysis of the LV, reduce subjectivity and improve patient experience. We automatically segment the LV wall in cardiac MRI images with a Deep Convolutional Neural Network (DCNN). This algorithm first calculates the probability of a pixel belonging to the LV wall or background and then generates a label based on those probabilities without manual initialization. We then compare these results to the results obtained with another DCNN initialization method using Gabor filters. With Gabor DCNN we obtain an accuracy of 0.97, specificity of 0.984, sensitivity of 0.841 and mean accuracy of 0.902. This shows that Gabor filters perform better than random filters in the DCNN for LV segmentation.


[Carl Troester, 1880-83 as veterinarian in Tokyo].
Carl Troester (1856-1928), royal Prussian junior veterinary surgeon, has been sent by command of His Majesty to Tokyo to teach at the Agricultural Faculty Japanese students in veterinary medicine. Instruction language is English. The course of instruction comprises 36 hours per week. He gains the acknowledgement of his pupils and in 1883, on dismissal he has been received by the Tenno. His career at the military veterinary academy in Berlin leads to the position of veterinary brigadier and professor. With the construction of the sanitary institute he has raised himself a memorial.


Clinical outcome in measles patients hospitalized with complications.
Measles is a highly communicable viral illness and is common cause of childhood mortality and morbidity. Keeping in view the high prevalence of measles in the developing world, we carried out this study to look into the complicated measles cases and clinical outcome in patients admitted in children ward of Ayub Teaching Hospital. Detailed history and physical examination of all the hospitalized patients with complication of measles were recorded in a proforma. Immunization and nutritional status of each admitted patient was assessed and the clinical outcome of measles was compared with demographic profile. One hundred thirty six hospitalized patients with complications of measles were studied. There was 60.3% male and 57.3% of patients were vaccinated against measles. Malnourished patients were 71.35% and had longer hospital stay (> 5 days). Pneumonia (39.7%) and diarrhoea (38.2%) were the commonest complications. Seven children died and encephalitis (57.1%) was the commonest cause of death. The most common complications of measles are pneumonia and diarrhoea with dehydration requiring admission. Malnutrition results in more complications and longer hospital stay. Mortality is significantly associated with encephalitis.


A simple rapid detection method of DNA based on ligation-mediated real-time fluorescence PCR.
Polymerase chain reaction (PCR) has been widely used for detecting long chain DNA or RNA of viruses, bacteria and cytokines, but it is difficult to detect DNA or RNA with short length sequences. In this work, we developed a simple and rapid detection method for short length DNA sequences in complicated matrices based on ligation-mediated PCR. Two probes, both designed as 52 bases and respectively partly complementary to the half-sequence of target DNA, could simultaneously hybridize to the target DNA, then to be ligated by T4 DNA ligase to form a long chain as PCR template for amplification. With the specific hybridization of the two probes and target DNA, and the PCR going on, a target with 16 bases was selectively detected with content as low as 200 fM, and the linear range spanned over five orders of magnitude. This method was successfully applied to the detection of target DNA in complicated biological samples such as cell lysate with satisfactory results.


Machine Learning's Application in Deep Brain Stimulation for Parkinson's Disease: A Review.
Deep brain stimulation (DBS) is a surgical treatment for advanced Parkinson's disease (PD) that has undergone technological evolution that parallels an expansion in clinical phenotyping, neurophysiology, and neuroimaging of the disease state. Machine learning (ML) has been successfully used in a wide range of healthcare problems, including DBS. As computational power increases and more data become available, the application of ML in DBS is expected to grow. We review the literature of ML in DBS and discuss future opportunities for such applications. Specifically, we perform a comprehensive review of the literature from PubMed, the Institute for Scientific Information's Web of Science, Cochrane Database of Systematic Reviews, and Institute of Electrical and Electronics Engineers' (IEEE) Xplore Digital Library for ML applications in DBS. These studies are broadly placed in the following categories: (1) DBS candidate selection; (2) programming optimization; (3) surgical targeting; and (4) insights into DBS mechanisms. For each category, we provide and contextualize the current body of research and discuss potential future directions for the application of ML in DBS.


Occlusal indices revisited.
With the increased interest in measuring the need for orthodontic treatment and the quality of the outcome of orthodontic care, the difficulties in using Grainger's Treatment Priority Index (TPI) to screen children in their tenth year is considered. The first part of the study investigated the level of validity of the TPI using 137 study models and three orthodontists. In the light of the results obtained, the TPI was modified. The clinical judgement of a further two orthodontists was compared with the scores obtained form the modified TPI, using another 121 study models. Three Community Dental Officers were employed initially to assess the training needs for personnel who were not trained in orthodontics. A further five Community Dental Officers were involved in the final training programmes. It was concluded that it will be very difficult to produce an index which considers all aspects of malocclusion and which can be used consistently by personnel untrained in orthodontics.


Discovery of a Novel Muscarinic Receptor PET Radioligand with Rapid Kinetics in the Monkey Brain.
Positron emission tomography (PET), together with a suitable radioligand, is one of the more prominent methods for measuring changes in synaptic neurotransmitter concentrations in vivo. The radioligand of choice for such measurements on the cholinergic system is the muscarinic receptor antagonist N-[1-11C]propyl-3-piperidyl benzilate (PPB). In an effort to overcome the shortcomings with the technically cumbersome synthesis of [11C]PPB, we designed and synthesized four structurally related analogues of PPB, of which (S,R)-1-methylpiperidin-3-yl)2-cyclopentyl-2-hydroxy-2-phenylacetate (1) was found to bind muscarinic receptors with similar affinity as PPB (3.5 vs 7.9 nM, respectively). (S,R)-1 was radiolabeled via N-11C-methylation at high radiochemical purity (>99%) and high specific radioactivity (>130 GBq/μmol). In vitro studies by autoradiography on human brain tissue and in vivo studies by PET in nonhuman primates demonstrated excellent signal-to-noise ratios and a kinetic profile in brain comparable to that of [11C]PBB. (S,R)-[11C]1 is a promising candidate for measuring changes in endogenous acetylcholine concentrations.


Image findings of bisphosphonate related osteonecrosis of jaws comparing with osteoradionecrosis.
The aim of this study was to evaluate image characteristics of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and compare these with osteoradionecrosis (ORN). 34 patients with BRONJ and 16 patients with ORN were included in this study. We investigated the CT and dental panoramic radiograph (DPR) images for osteolysis, osteosclerosis, sequestration, periosteal reaction, pathological fracture and spread of soft tissue inflammation around the jaws. Osteolysis, osteosclerosis, sequestration and spread of soft tissue inflammation around the jaws were common radiological features in both BRONJ and ORN. Osteolysis and spreading of soft tissue inflammation around the jaws were predominant in ORN, and by contrast osteosclerosis was predominant in BRONJ. Periosteal reaction was established in 15 of the 34 BRONJ cases, but none in the ORN cases. Pathological fractures were observed in 6 of 16 ORN cases, but none in BRONJ cases. CT was better for detection than DPR for osteolysis, osteosclerosis, sequestration and periosteal reactions. Image findings of BRONJ were characterized as a severe sclerotic change combined with osteolysis, sequestration, periosteal reaction and spread of soft tissue inflammation around the jaws.


Immunology of Multiple Sclerosis.
Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the central nervous system (CNS). A complex genetic background with the HLA-DR15 haplotype as the main genetic risk factor and over 100 mostly immune-related minor risk alleles as well as several environmental factors contribute to the etiology of MS. With respect to pathomechanisms, autoimmune inflammation in early MS is primarily mediated by adaptive immune responses and involves autoreactive T cells, B cells, and antibodies, while the later, chronic stages of MS are characterized by a compartmentalized immune response in the CNS with activated microglia and macrophages. A host of immune cells and mediators can contribute to the autoimmune process, but CNS-related factors such as localization of lesions, vulnerability of oligodendrocytes, neurons/axons, and secondary metabolic changes all play a role in the heterogeneous expression of the disease, including different pathologic lesion patterns, neuroimaging findings, disease courses, and severity and response to treatment.


Regioselective Deposition of Metals on Seeds within a Polymer Matrix.
We use scanning probe block copolymer lithography in a two-step sequential manner to explore the deposition of secondary metals on nanoparticle seeds. When single element nanoparticles (Au, Ag, Cu, Co, or Ni) were used as seeds, both heterogeneous and homogeneous growth occurred, as rationalized using the thermodynamic concepts of bond strength and lattice mismatch. Specifically, heterogeneous growth occurs when the heterobond strength between the seed and growth atoms is stronger than the homobond strength between the growth atoms. Moreover, the resulting nanoparticle structure depends on the degree of lattice mismatch between the seed and growth metals. Specifically, a large lattice mismatch (e.g., 13.82% for Au and Ni) typically resulted in heterodimers, whereas a small lattice mismatch (e.g., 0.19% for Au and Ag) resulted in core-shell structures. Interestingly, when heterodimer nanoparticles were used as seeds, the secondary metals deposited asymmetrically on one side of the seed. By programming the deposition conditions of Ag and Cu on AuNi heterodimer seeds, two distinct nanostructures were synthesized with (1) Ag and Cu on the Au domain and (2) Ag on the Au domain and Cu on the Ni domain, illustrating how this technique can be used to predictively synthesize structurally complex, multimetallic nanostructures.


Hypo-fibrinolysis in patients with hypertension and elevated cholesterol.
To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI.


Assessment of the effects of sodium nitrate (NaNO3) on the reproductive system, liver, pancreas, and kidney of male rats.
Nitrate (NO3) toxicity is a serious global issue that results in impairment of physiological systems of our body. The present study aimed to investigate the effects of different concentration of NaNO3 (10, 100, 500 and 1000 mg/kg bw) on the male reproductive system, liver, kidney and pancreas. Adult male Wistar rats were divided into five groups of five animals each (n = 5). The first group served as controls. The second, third, fourth and fifth groups of rat were orally intubated with 10, 100, 500 and 1000 mg/kg bw of NaNO3 for 52 days. After the treatment period, the rats were sacrificed and NO3 induced alterations on selected organs were assessed. There was a dose dependent decrease in sperm motility, serum concentration of testosterone, body weight and organ weight, and increase in abnormal sperm morphology in the NaNO3 treated groups compared with the controls. Further, histological analysis confirmed that NO3 induced toxicity. Shrunken seminiferous tubules and loss of spermatids in testes, shrinkage of acinar cells of the pancreas, sinusoidal congestion and necrosis in the liver, atrophy of glomeruli and congestion of renal tubules of the kidney were the histological alterations observed in rats treated with100 and 500 mg/kg NaNO3. However, 100% mortality was observed in rats treated with 1000 mg/kg NaNO3. The present study clearly demonstrated the toxic effects of NaNO3 on both the reproductive system and other organs of the body. The study might inform human studies; where in the chances of male infertility may be more a problem for individuals in areas with NO3-rich ground water.


Toll-like receptors expression and signaling in glia cells in neuro-amyloidogenic diseases: towards future therapeutic application.
Toll-like receptors (TLRs) are known to be expressed by innate immune response cells and to play a critical role in their activation against foreign pathogens. It was recently suggested that TLRs have an important role in the crosstalk between neurons and glial cells in the central nervous system (CNS). TLR signaling was reported to be associated with a yin-yang effect in the CNS. While TLR signaling was linked to neurogenesis, it was also found to be involved in the pathogenesis of neurodegenerative diseases. This paper will focus on TLR signaling in glial cells in neurodegenerative diseases such as Alzheimer's disease, prion diseases, amyotrophic lateral sclerosis, and Parkinson's disease. Understanding the pattern of TLR signaling in the glial cells may lead to the identification of new targets for therapeutic application.


[Complete atrioventricular block disclosing Fabry's disease].
Fabry's disease is a hereditary sex-linked sphinglopidosis characterised by abnormal cellular lipid overload in most organs due to deficiencies in enzymes implicated in the catabolism of certain neutral glycolipids. There are two main clinical forms; cardiovascular manifestations usually congestive cardiac failure, and renal manifestations progressing to renal failure and death due to uraemic coma. The authors report a case presenting with juvenile, symptomatic complete infrahisian atrioventricular block. They describe the different cardiovascular complications of Fabry's disease from a review of the medical literature.


Prejudice against international students: the role of threat perceptions and authoritarian dispositions in U.S. students.
International students provide a variety of benefits to higher education institutions within the United States (J. J. Lee, 2007; J. J. Lee & C. Rice, 2007). Despite these benefits, many international students experience prejudice and discrimination by American students. The purpose of the present study was to examine several potential predictors of prejudice against international students: perceptions of international students as symbolic and realistic threats, right-wing authoritarianism, and social dominance orientation. A simultaneous regression analysis that the authors based on 188 students at a Southwestern university revealed that perceptions of symbolic and realistic threats and social dominance orientation were each positive and significant predictors of prejudice. Mediation analyses suggested that the effects of right-wing authoritarianism on prejudice is fully mediated through perceived symbolic threat and partially mediated by realistic threat.


Gold(III)-catalyzed enynamine-cyclopentadiene cycloisomerization with chirality transfer: an experimental and theoretical study indicating involvement of dual Au(III) push-pull assisted cis-trans isomerism.
A synthetic approach for asymmetric ring-fused cyclopentadienes (Cps) with a chiral carbon at the ring junction has been established from chiral enynamines by achiral Au(III) catalysis. On the basis of experimental and theoretical data, the proposed mechanistic pathway from enynamines to Cps occurs via a Au(III) ene cis-trans isomerization step. Computational studies at DFT and NEVPT2 levels advocate that the cis-trans isomerization step proceeds via a dual Au(III) push-pull assisted intermediate with a low computed rotation barrier. The chirality transfer occurs through a helical-shaped transition state with allenic character. The scope of the catalysis encompasses sterically bulky enynamines including terpene natural products.


Dialysis in neonates with inborn errors of metabolism.
Certain inborn errors of metabolism become manifest during the neonatal period by acute accumulation of neurotoxic metabolites leading to coma and death or irreversible neurological damage. Outcome critically depends on the immediate elimination of the accumulated neurotoxins. Recent technological progress provides improved tools to optimize the efficacy of neonatal dialysis. We report our experience with continuous venovenous haemodialysis (CVVHD) in six neonates with hyperammonaemic coma due to urea-cycle disorders or propionic acidaemia and in one child with leucine accumulation due to maple-syrup urine disease (MSUD), in comparison with five patients managed by peritoneal dialysis (PD) (2 hyperammonaemia, 3 MSUD). Application of a new extracorporeal device specifically designed for use in small children permitted the establishment of stable blood circuits utilizing small-sized catheters, and the tight control of balanced dialysate flows over wide flow ranges. Plasma ammonia or leucine levels were reduced by 50% within 7.1 +/- 4.1 h by CVVHD and within 17.9 +/- 12.4 h by PD (P<0.05). Also, total dialysis time was shorter with CVVHD (25 +/- 21 h) than with PD (73 +/- 35 h, P<0.02). A comparison of the CVVHD results with published literature confirmed superior metabolite removal compared to PD, and suggested comparable efficacy as achieved with continuous haemofiltration techniques. Apart from accidental pericardial tamponade during catheter insertion in one case, no major complications were noted with CVVHD. In three of the five PD patients, dialysis was compromised by mechanical complications. None of the MSUD patients but four children with urea-cycle disorders died, two during the acute period and two later during the first year of life, with signs of severe mental delay. Of the eight children presenting with hyperammonaemic coma, the four with the most rapid dialytic ammonia removal rate (50% reduction in < 7 h) survived with no or moderate mental retardation, whereas slower toxin removal was always associated with a lethal outcome. Simulation studies showed that the efficacy of neonatal CVVHD is limited mainly by blood-flow restrictions. While CVVHD is the potentially most efficacious dialytic technique for treating acute metabolic crises in neonates, utmost care must be taken to provide an adequately sized vascular access.


Comparison of the Molecular Weights of Proteins Synthesized by Isolated Chloroplasts with Those Which Appear during Greening in Zea mays.
The proteins of prolamellar bodies of etioplasts and of thylakoid membranes of greening and mature chloroplasts from Zea mays were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three classes of proteins were distinguished: those present in etioplasts and disappearing during greening, those absent in etioplasts and appearing during greening, and those present in both etioplasts and chloroplasts. The largest number of proteins belonged to this last class.The molecular weights of chloroplast thylakoid proteins were compared to the molecular weights of the membrane-associated proteins synthesized by isolated, mature chloroplasts. Thirteen of the 15 to 20 membrane-bound proteins made by isolated chloroplasts corresponded in size to proteins present in chloroplasts. Most of the 13 are present in both etioplasts and chloroplasts although a few were the same size as proteins which increase during greening. Production of most of the membrane proteins made in the plastids is not stringently regulated by light in vivo. The polypeptide subunits of the light-harvesting pigment-protein complex, the most abundant proteins of the chloroplast thylakoids, were absent from etioplasts. They were not synthesized by isolated chloroplasts.


Programmed necrosis and necroptosis signalling.
In recent years, the paradigm of cell death regulation has changed. Nowadays, not only apoptosis but also several forms of necrosis (e.g. necroptosis) are considered to be regulated. The central roles of receptor-interacting serine/threonine protein kinase1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein, and the molecular signalling platforms in which these molecules participate, are being intensively studied. In particular, the role of RIPK1, being both a kinase and a scaffold molecule, in different cell death regulatory complexes is of great relevance for the field. This minireview aims to introduce the emerging and dynamic field of necroptosis to the reader, with a specific focus on intracellular signalling pathways involved in this process.


Potential pitfalls in the frozen section evaluation of parenchymal margins in nephron-sparing surgery.
With advances in radiographic imaging, there has been an increase in the incidental detection of small renal cell carcinomas, with a resultant increase in partial nephrectomies for these tumors. Partial nephrectomy often necessitates assessment of renal parenchymal margins by frozen section. To determine the most common problematic "lesions" encountered on renal parenchymal margins, we evaluated all diagnostically challenging frozen sections that had been referred to a genitourinary pathologist. Frozen sections with detached atypical cells and crushed tubules were the most common lesions that presented diagnostic uncertainty. We found that normal constituents of renal parenchyma, namely tubules and glomeruli, can be mistaken for neoplasia. Neoplastic tubules of low-grade renal cell carcinomas may be misinterpreted as thickly cut, crushed benign tubules, and the significance of tubulopapillary "adenomas" in frozen sections is unclear. The present report highlights diagnostic difficulties that pathologists may encounter on frozen sections of renal parenchymal margins.


Fibrillary (immunotactoid) glomerulopathy. A possible role for kappa light chain in its etiology and/or pathogenesis.
The initial clinical manifestations, course, and immunopathologic findings of renal biopsies of nine patients with fibrillary glomerulopathy are reported. Their first symptoms and courses were variable, but proteinuria and renal failure were common. While some patients required hemodialysis soon after coming for treatment, others progressed to renal failure over several years. Three patients had monoclonal gammopathy; one of them had an isolated, transient, Bence-Jones proteinuria. The main pathologic features are glomerular enlargement, mesangial expansion, and mild hypercellularity. Congo red and thioflavin stains were negative. Kappa chain, either alone or with lambda chain and IgG, were the predominant immunoreactants. Ultrastructurally, the presence of coarse fibrils of 15-25 nm was characteristic, but there were also granular deposits in the capillary wall that occurred in a band-like pattern in the inner half of the glomerular basement membrane in a manner similar to the deposits seen in light chain deposit disease. The immunofluorescence and ultrastructural findings suggest that light chains (especially kappa) may be significant in the pathogenesis of fibrillary glomerulopathy and that there may be a relationship with light chain deposit disease.


The anatomy of the lacrimal portion of the orbicularis oculi muscle (tensor tarsi or Horner's muscle).
Horner's muscle (the palpebral part of the orbicularis oculi muscle) has a fan-shaped origin in the lacrimal bone. Its muscle fibers are oriented from 160 to 210 degrees relative to the ear-eye plane and converge towards the medial palpebral commissure. Then the muscle divides into superior and inferior bundles of fibers. Some of the lower fibers participate in the formation of the superior bundle and some of the higher fibers participate in the formation of the inferior bundle and, thus, some of Horner's muscle is twisted. Each bundle courses laterally to the lateral palpebral commissure and has three insertions. The first insertion is located at the medial margin of the tarsi. The second insertion is into the subcutaneous tissue along the palpebral margins. Minute fascicles of Horner's muscle are fastened to the palpebral margins. The third insertions are into the lateral palpebral ligament and subcutaneous connective tissue of the lateral commissure. Serial histological sections of a fetus at 14 to 16 weeks gestation revealed that the extent of the envelope formed by Horner's muscle around the lacrimal canaliculus decreases gradually from the lacrimal papilla to the lacrimal sac. The various observations suggest the following roles for Horner's muscle: (1) it closes the medial canthus of the eye and closes the lacrimal punctum; (2) it pulls the tarsus medially; (3) it tautens the palpebral margins and presses against the eyeball; and (4) it squeezes the lacrimal canaliculus with a decreasing gradient of pressure from the lacrimal papilla to the lacrimal sac. These actions are likely to be important for the flow of lacrimal fluid in the lateral to medial direction on the eyeball, for maintenance of the thickness of tear film over the cornea, for opening and closing of the lacrimal punctum, and for passage of the lacrimal fluid from the canaliculus to the sac. Horner's muscle appears, thus, to be a muscle of prime importance in all phases of the flow of lacrimal fluid.


[Tension-free surgery of femoral hernias using the Lichtenstein method].
Based on 12 operations, the author report on the advantages of "plug tension-free" plastic operations. The femoral canal is along its entire course sealed by a cylinder of rolled up polyester net. This operation reduces the postoperative discomfort and danger of the development of a relapse.


A new Occupational Safety and Health Administration directive regarding H1N1 influenza in the workplace.
This article addresses the following aspects of a new Occupational Safety and Health Administration (OSHA) directive associated with H1N1 in the workplace: the recordability of H1N1 exposure in the workplace; the need for employers to have a pandemic plan that addresses the identification and management of H1N1 exposure risk to employees; the respiratory protection requirements of an exposure control plan; OSHA workplace inspections in response to exposure complaints or fatalities associated with H1N1; and the availability of OSHA compliance guidance for employers.


Preparation of Solid, Substituted Allylic Zinc Reagents and Their Reactions with Electrophiles.
The treatment of various allylic chlorides or bromides with zinc dust in the presence of lithium chloride and magnesium pivalate (Mg(OCOtBu)2) in THF affords allylic zinc reagents which, after evaporation of the solvent, produce solid zinc reagents that display excellent thermal stability. These allylic reagents undergo Pd-catalyzed cross-coupling reactions with PEPPSI-IPent, as well as highly regioselective and diastereoselective additions to aryl ketones and aldehydes. Acylation with various acid chlorides regioselectively produces the corresponding homoallylic ketones, with the new C-C bond always being formed on the most hindered carbon of the allylic system.


Evaluating the Risk Factors for Porcine Epidemic Diarrhea Virus Infection in an Endemic Area of Vietnam.
Porcine epidemic diarrhea virus (PEDV) causes enteritis, vomiting, watery diarrhea, and high mortality in suckling pigs, threatening the swine industry. Porcine epidemic diarrhea (PED) re-emerged globally in 2013 in many important swine-producing countries in Asia and the Americas. Several studies have identified the risk factors for the spread of PEDV in acute outbreaks. However, limited information is available on the risk factors for the transmission of PEDV in endemic regions. We hypothesized that poor biosecurity, location, and some social or cultural practices are the main risk factors for PEDV transmission in the Vietnamese pig population. The aim of this study was to evaluate the potential risk factors for the transmission of PEDV in an endemic area in Vietnam. In this case-control study, questionnaires containing 51 questions were completed for 92 PEDV-positive and 95 PEDV-negative farms. A logistic regression analysis was performed to assess the risk factors associated with PEDV infection. Province and the total number of pigs were included as random effects to determine their influence on the risk of PEDV infection. Twenty-nine variables of interest that have been associated with PEDV status were analyzed in a univariate analysis (P <0.20), with backward stepwise selection. Only three of these 29 variables in four models remained significant PEDV risk factors in the final model: farrow-to-wean production type, distance from the farm to the slaughterhouse (<1,000 m), and the presence of chickens on site (P <0.05). This is the first study to identify the main risk factors for PEDV infection in an endemic area. Our findings suggest that hygiene measures should be strictly implemented on farms for the effective control and prevention of PEDV infection.


Structural characterization of the early indoleacetic acid-inducible genes, PS-IAA4/5 and PS-IAA6, of pea (Pisum sativum L.).
Two early auxin-inducible genes (PS-IAA4/5 and PSIAA6) from pea were cloned using previously isolated complementary DNA sequences. They are present in single copy per haploid genome, and are members of a large divergent multigene family that encodes similar proteins. The genes were structurally characterized and sequence analysis of their 5'-flanking regions revealed the presence of several highly conserved sequences found in various auxin-regulated genes from other plant species. Their coding regions are interrupted by three and two introns, respectively. Introns two and three of PS-IAA4/5 and introns one and two of PS-IAA6 are located in identical positions. These genes encode proteins of 189 (21,036 Da) and 179 (20,330 Da) residues that are 46% identical. They also share a significant degree of identity (42 to 80%) with other proteins encoded by auxin regulated genes in soybean, mungbean and Arabidopsis thaliana. All proteins contain four conserved domains ranging in size from 9 to 43 amino acids. Their most prominent feature is the presence of a highly charged N terminus consisting of two clusters of acidic residues separated by a cluster of basic amino acids.


Cerebrospinal fluid changes and clinical features of aseptic meningitis in patients with Kawasaki disease.
To assess the distinguishing features of aseptic meningitis (AM) in patients with Kawasaki disease (KD) compared with bacterial meningitis (BM) patients. Thirty-eight patients with KD and 126 patients with BM were retrospectively investigated. The following clinical manifestations and laboratory parameters were compared between the two groups: duration of fever before lumbar puncture, conjunctival injection, oral cavity changes, rash, cervical lymphadenopathy and extremity changes, vomiting, front fontanel bulging, neck stiffness, leukocyte number, hemoglobin level, platelet number, C-reactive protein level, cerebrospinal fluid (CSF) content, liver enzyme level, and urinalysis. Vomiting and neck stiffness were more prevalent in patients with BM. KD patients with AM showed elevated blood leukocyte numbers and C-reactive protein levels in the early febrile stage. CSF glucose was significantly lower in patients with BM compared with KD patients with AM. Receiver operating characteristic curve analysis showed that the optimal cutoff value of CSF glucose for discrimination of BM and AM/KD was 2.945 mmol/L, with a sensitivity of 84.2% and a specificity of 71.4%. Detailed investigations of clinical manifestation and laboratory parameters are necessary to distinguish AM and BM in patients with KD. Decreased CSF glucose is a potential indicator of BM.


DNA Damage and Oxidative DNA Damage in Inflammatory Bowel Disease.
Inflammation has long been regarded as a major contributor to cellular oxidative damage and to be involved in the promotion of carcinogenesis. We aimed to investigate the oxidative damage in inflammatory bowel disease [IBD] patients through a case-control and prospective study involving 344 IBD patients and 294 healthy controls. DNA damage and oxidative DNA damage were measured by comet assay techniques, and oxidative stress by plasmatic lipid peroxidation, protein carbonyls, and total antioxidant capacity. Higher DNA damage [p < 0.001] was found both in Crohn's disease [CD] (9.7 arbitrary units [AU]; interquartile range [IQR]: 6.2-14.0) and ulcerative colitis [UC] [7.1 AU; IQR: 4.4-11.7], when compared with controls [5.4 AU; IQR: 3.8-6.8], and this was also the case with oxidative DNA damage [p < 0.001] [CD: 3.6 AU; IQR: 1.8-6.8; UC: 4.6 AU; IQR: 2.4-8.1], when compared with controls: 2.3 AU; IQR: 1.2-4.2]. Stratifying patients into groups according to therapy (5-aminosalicylic acid [5-ASA], azathioprine, anti-TNF, and combined therapy [azathioprine and anti-TNF]) revealed significant between-group differences in the level of DNA damage, both in CD and UC, with the combined therapy exhibiting the highest DNA damage levels [11.6 AU; IQR: 9.5-14.3, and 12.4 AU; IQR: 10.6-15.0, respectively]. Among CD patients, disease behaviour [B1 and B2], and age at diagnosis over 40 years [A3] stand as risk factors for DNA damage. For UC patients, the risk factors found for DNA damage were disease activity, treatment, age at diagnosis under 40 years [A1 + A2] and disease locations [E2 and E3]. In IBD there is an increase in DNA damage, and treatment, age at diagnosis and inflammatory burden seem to be risk factors.


Esperanza y Vida: training lay health advisors and cancer survivors to promote breast and cervical cancer screening in Latinas.
The use of lay health advisors (LHAs) to promote community-based health education programs is well documented and is considered an effective way to reach underserved communities. Esperanza y Vida (Hope & Life) is an educational outreach program to increase breast and cervical cancer screening for diverse Latinas. It incorporates Latino LHAs (men and women) and cancer survivor role models, sobrevivientes, in the program delivery. An interactive training program, conducted by bilingual staff across three sites (Little Rock, Arkansas; Buffalo, New York and New York City) included 74 sobrevivientes and LHAs who were recruited and trained. All training attendees completed an initial application assessing socio-demographics, experience and availability as well as, true/false surveys at the beginning (pre-) and end of the training (post-) measuring knowledge levels of breast and cervical cancer health. Data analysis indicated a significant increase of both breast and cervical cancer knowledge for attendees trained as LHAs (pre = 60%; post = 80%; p = 0.000), whereas sobrevivientes had a higher baseline knowledge of breast health (74%), and therefore did not show a significant increase following training (79%). However, sobrevivientes did display a significant increase in cervical cancer knowledge (p = 0.003). These findings demonstrate the impact of training and how LHAs may be recruited at different levels of knowledge and experience and be successfully trained in key program elements. Moreover, results indicate that sobrevivientes may be impacted differently, or require variations in training approaches. This information can be useful in developing and customizing curriculum for future lay health training programs.


[Expression and significance of P-glycoprotein, glutathione S-transferase-pi and Topoisomerase II in gastric carcinomas].
Multi-drug resistance(MDR) is the most important failing reason of tumor chemotherapy, the substance that P-glycoprotein(P-gp), glutathione S-transferase-pi(GST-pi), Topoisomerase II (Topo II) etc was the fundamental substances producing MDR. Gastric carcinoma is the relatively familiar malignancy, the report was relatively fewness that the expression of P-gp, GST-pi and Topo II by means of immunohistochemistry were associated with in the gastric carcinomas of previously untreated patients. This study was designed to investigate the expression and significance of P-gp, glutathione S-transferase-pi(GST-pi) and Topoisomerase II(Topo II) in gastric carcinomas. Seventy-five human gastric carcinomas of previously untreated patients were studied for the expression of P-gp, GST-pi and Topo II by means of immunohistochemistry. The expression of P-gp, GST-pi and Topo II were 76.0%, 85.3% and 68.0% in gastric carcinoma tissues. There was no significant relationship between the expression levels and age, sex, location of tumor and depth of tumor invasion. Positive rate was higher in glandular-form carcinoma than that in mucoid carcinoma, signet-ring cell carcinoma and poorly differentiated carcinoma (P < 0.05). There was a significant relationship between the lymph node involvement and the higher expression of P-gp, GST-pi, lower expression of Topo II. There is a correlation between the expression of P-gp, GST-pi, Topo II and histologic subtypes, the expression may also related to the differentiation and metastasis of the gastric carcinomas.


Ajmaline Testing and the Brugada Syndrome.
Brugada syndrome (BrS) diagnosis requires the presence of a typical type 1 ECG pattern. Owing to the spontaneous ECG variability, the real BrS prevalence in the general population remains unclear. The aim of the present study was to evaluate the prevalence of positive ajmaline challenge for BrS in a cohort of consecutive patients who underwent electrophysiological evaluation for different clinical reasons. All consecutive patients from 2008 to 2019 who underwent ajmaline testing were prospectively included. A total of 2,456 patients underwent ajmaline testing, 742 (30.2%) in the context of familial screening for BrS. In non-familial screening group (1,714) ajmaline testing resulted positive in 186 (10.9%). Indications for ajmaline testing were: suspicious BrS ECG in 23 cases (12.4%), palpitations in 27 (14.5%), syncope in 71 (38.2%), presyncope in 7 (3.8%), family history of sudden cardiac death in 18 (9.7%), documented ventricular arrhythmias in 12 (6.5%), unexplained cardiac arrest in 4 (2.2%), atrial fibrillation in 16 (8.5%), brady-arrhythmias in 1 (0.5%), and cerebrovascular accidents in 7 (3.7%). Compared with the overall population, ajmaline testing positive patients were younger (42.8 ± 15.5 vs 48.9 ± 20.4; p <0.001) and more frequently male (65.1% vs 56.3%; p = 0.023). Implantable cardioverter defibrillator was implanted in 84 patients (45.2%). During a median follow-up of 42.4 months, 12 appropriate shocks and 13 implantable cardioverter defibrillator related complications were reported. In conclusion, the BrS was diagnosed in an unexpected high proportion of patients that underwent ajmaline testing for a variety of cardiovascular symptoms. This can lead to an adequate counseling and clinical management in BrS patients.


Enhancement of cyclization quantum yields of perfluorodiarylethenes via weak intramolecular interactions.
The weak intramolecular F∙∙∙N and S∙∙∙N interactions in the novel pyridine-containing perfluorodiarylethenes achieved high cyclization quantum yields in solutions. While the F∙∙∙N interactions stabilize the photoreactive conformation, the S∙∙∙N contacts contribute from the energetic aspect.


Reverse caps in Medicare encourage primary care, better align incentives.
If your medical group is seeing specialty costs spiral out of control in Medicare, a reverse capitation arrangement may help. Paying primary care providers fee-for-service--and specialty providers capitation--may better align your group's incentives and promote better use of low-cost primary care services for seniors. See if the methodology is right for you.


Large omental metastases of a gastrointestinal stromal tumor.
Gastrointestinal stromal tumors are rare tumors, originating from the interstitial cells of Cajal. They are the most common mesenchymal tumors of the gastrointestinal tract. Metastatic tumor is treated with imatinib mesylate. A case of large metastases of a gastrointestinal stromal tumor to the omentum, diagnosis and treatment principles are presented in this case report.


[Relationship between clinical characteristics of lung cancer patients regarding their occupational exposure].
To study the relationship between clinical characteristics of lung cancer patients and their occupational exposure. 2110 workers (≥ 20 years) who had been engaged in occupation that were exposed to risk factors of lung cancer, were asked to fill in questionnaires which included social demographic characteristics, length of service, smoking history and habits etc. 378 cases with lung cancer admitted in the Tangshan Worker's Hospital were selected and their clinical data including general information, symptoms or signs other than lungs, CT findings, histological type of the tumor, metastasis of tumors etc. were compared between the occupational exposure group and the control group. The rate of lung cancer was 29.43% (621/2110) among the workers with occupational exposure, and in men it was higher than in women (P > 0.05). There were significant differences seen in the rates of lung cancer with different age, smoking history/habits and years of employment among workers having had the histories of occupational exposure (P < 0.01). With CT findings, the rate of obstructive emphysema in the occupational exposure group (36.91%) was higher than in the control group (18.78%), (P < 0.01). Pathologically, squamous cell carcinoma (36.24%) appeared to be higher than it did in the control group (28.38%). The rate of pleural metastasis in the occupational exposure group was 14.09%, while it was 7.42% (P < 0.05) in the control group. People, having had occupational exposure, showed an association between the rate of lung cancer and factors as: excessive smoking, advanced age and long histories of occupational exposure. Squamous cell carcinoma with obstructive emphysema and pleural metastasis appeared to be dominantly seen.


[Brain sonographic findings in tuberous brain sclerosis. A comparison with roentgenologic images and pathologic-anatomic findings].
Ultrasound examination of a case of tuberous sclerosis is described. The results are compared to plain skull roentgenography, CT and pathological anatomical findings. Apart from the well known advantages of sonography (absence of radiation load, easy and quick practicability of control nearly without strain to the patient) the comparison shows that ultrasound offers a better chance to evaluate the structure of gliomatous masses and their relationship to the adjacent tissues. In connection with the pathological microscopical picture and the results of sonography we drew the conclusion that the paraventricular calcifications in CT so far described are most possibly gliomatous proliferations with densities around 100 HU. Using CT as a diagnostic tool alone it is not possible to distinguish between gliomatous proliferation and calcification in tuberous sclerosis.


Regulation of transferrin receptor expression in myeloid leukemia cells.
Surface transferrin (Tf) receptors are displayed by cultured human hematopoietic cells and provide Fe required for cell growth. Cell cycle status, cell density in culture, exposure to Fe, and differentiation alter Tf receptor display by myeloid leukemia cells. To investigate mechanisms controlling Tf receptor expression, rates of receptor synthesis and steady-state mRNA levels were measured in HL60 promyelocytic cells grown in serum and serum-free media or after differentiation in response to dimethylsulfoxide (DMSO). Although surface binding sites were unchanged during the first three days in culture with serum or in serum-free media containing Tf, by the third day, rates of receptor biosynthesis and steady-state mRNA levels declined, consistent with cell density-dependent, receptor regulation. Cells grown with soluble Fe instead of Tf showed reduced Tf binding sites, rates of receptor synthesis, and Tf receptor mRNA. When cells grown with Fe were subcultured, Tf receptor mRNA levels increased within 15 minutes and peaked by 24 hours. This was followed by a decline in receptor and gene expression so that by three days cells grown in the presence of Fe expressed approximately four times fewer receptors and had half the rates of Tf receptor synthesis and mRNA levels of cells grown in serum or Tf. Cells treated with DMSO showed a rapid decline in surface receptors, receptor synthesis, and steady-state mRNA levels. Modulation of Tf receptor expression was not due to redistribution between the cell surface and an internal receptor pool. In each instance, concurrent assessment of N-ras transcripts showed that changes in Tf receptor mRNA levels were not due to generalized alterations in protein synthesis. Exposure of cells grown in Fe or treated with DMSO to cycloheximide did not alter Tf receptor mRNA levels, thereby suggesting that receptor expression was not regulated by posttranscriptional processes dependent on protein synthesis. Actinomycin D inhibition of Tf receptor mRNA was compatible with a transcript half-life of approximately 2.2 hours. Nuclear transcription studies showed reduced rates of Tf receptor transcription after culture with Fe or exposure to DMSO. The present studies show complex patterns of Tf receptor gene regulation in cultured myeloid leukemia cells and demonstrate that transcriptional regulation is a major mechanism controlling Tf receptor gene expression in response to Fe and differentiation.


An Analysis of Demographic and Triage Assessment Findings in Bushfire-Affected Koalas (Phascolarctos cinereus) on Kangaroo Island, South Australia, 2019-2020.
In the 2019-2020 Australian bushfires, Kangaroo Island, South Australia, experienced catastrophic bushfires that burnt approximately half the island, with an estimated 80% of the koala population lost. During and after the event, rescued koalas were triaged at a designated facility and a range of initial data were recorded including rescue location and date, sex, estimation of age, body condition and hydration, and assessment of burn severity (n = 304 records available). Koalas were presented to the triage facility over a span of 10 weeks, with 50.2% during the first 14 days of the bushfire response, the majority of which were rescued from regions of lower fire severity. Burns were observed in 67.4% of koalas, with the majority (60.9%) classified as superficial burns, primarily affecting the limbs and face. Poor body condition was recorded in 74.6% of burnt koalas and dehydration in 77.1%. Negative final outcomes (death or euthanasia, at triage or at a later date) occurred in 45.6% of koalas and were significantly associated with higher mean burn score, maximum burn severity, number of body regions burnt, poor body condition score, and dehydration severity. The findings of this retrospective study may assist clinicians in the field with decision making when triaging koalas in future fire rescue efforts.


Value of CD15 immunostaining in diagnosing Hodgkin's disease: a review of published literature.
The role of antibodies of CD15 as diagnostic markers of Hodgkin's disease was assessed from a review of the literature. A total of 571 cases of Hodgkin's disease and 386 cases of non-Hodgkin's lymphoma were included. The sensitivity of CD15 in detecting cases of Hodgkin's disease was 80% or 91% if cases of lymphocyte predominant Hodgkin's disease were excluded. The specificity of CD15 was only 80.6%, or in other words, 19.4% of cases of non-Hodgkin's lymphoma were CD15 positive. In an ideal test both the sensitivity and specificity would be 100% and if the test performance were no better than chance then they would both be 50%. It is concluded that CD15 immunostaining cannot be regarded as a sensitive or specific marker of Hodgkin's disease. Application of this formal method of analysis to other immunohistological reagents and panels of antibodies is discussed.


Baseline choroidal thickness as a short-term predictor of visual acuity improvement following antivascular endothelial growth factor therapy in branch retinal vein occlusion.
To evaluate the association between subfoveal choroidal thickness (SFCT) and branch retinal vein occlusion (BRVO) eyes treated with antivascular endothelial growth factor (anti-VEGF) therapy. Retrospective cohort study of treatment naïve BRVO eyes treated with 3 monthly anti-VEGF injections. All patients received enhanced depth imaging spectral-domain optical coherence tomography scans to determine SFCT and central macular thickness (CMT). Baseline predictors (particularly SFCT) for functional response (best-corrected visual acuity (BCVA) gain ≥2 lines) were assessed at 3 months using univariate and multivariate analyses. Forty eyes from 39 patients were included. Mean baseline SFCT was higher in functional responders (240.4±73.1 µm), compared with both non-responders (193.3±63.6 µm; p=0.036) and their corresponding fellow eye (202.2±67.1 µm; p=0.022). A higher baseline SFCT (for every 100 µm increase in SFCT) was found to be a positive predictor for functional response (regression coefficient: 1.1; p=0.03) on univariate analysis but not multivariate analysis. A worse baseline BCVA (for every 0.1 logMAR increase) was a positive predictor for visual improvement with an adjusted OR of 1.30 (95% CI 1.03 to 1.63; p=0.0009) on multivariate analysis. Patients with BRVO with a worse initial BCVA are most likely to achieve visual improvement following anti-VEGF therapy. Additionally, baseline SFCT may also help predict which patients with BRVO have favourable visual outcomes. Patients with an initial choroidal thickness thicker than their fellow eye are more likely to have short-term visual improvement following treatment.


Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials.
Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians. A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform. A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening. We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields.


A two-step mechanism for the interaction of Re lipopolysaccharide with erythrocyte membranes.
In this report, a unique model system that allows the investigation of the interaction of lipopolysaccharide (LPS) with erythrocyte membranes is described. Rabbit red blood cells exposed to S. minnesota (Re mutant) R595 LPS were rendered sensitive to the cationic antibiotic polymyxin B in a manner independent of the temperature of incubation of erythrocytes with LPS (subsequent addition of polymyxin B induced hemolysis of erythrocytes sensitized with LPS). Following sensitization of red blood cells with R595 LPS, a time-dependent decrease in susceptibility of the cells to polymyxin B-mediated hemolysis occurred, which was shown not to be the result of dissociation of LPS from rabbit erythrocytes. The demonstration that the decrease in sensitivity of red blood cells to polymyxin B was dependent on the temperature of incubation of LPS with red blood cells is not inconsistent with the proposal that the decrease in sensitivity is attributable to a hydrophobic rearrangement of lipid-rich R595 LPS within the lipid bilayer of the erythrocyte membrane. The importance of this putative rearrangement of LPS within cell membrane in cellular triggering of LPS is unknown.


Strategies for Promoting the Medical Device Industry in Korea: An Analytical Hierarchy Process Analysis.
This study examines the medical device industry in the context of the Fourth Industrial Revolution and identifies the key strategies and general directions for promoting this industry through analytical hierarchy process (AHP). It is based on discussions of the key issues with specialists such as doctors, medical device companies, hospital staff, professors, and government agencies in the medical device industry. A total of 18 responses were obtained from the survey, and an analysis was conducted on the results. Among the medical device strategies identified by the surveyed specialists, clarifying the application of regulations (access strategy), increasing R&D investment for the technological development of medical devices (expansion strategy), and increasing support for global market expansion (infrastructure expansion strategy) were found to have the highest priority. Based on the above, we suggest key strategies and directions for promoting the medical device industry.


Localization of protein kinase C alpha isoform expression in the human gastrointestinal tract.
Protein kinase C (PKC) includes a family of related proteins which constitutes a major signal transduction pathway. The aim of this study was to determine the localization of the PKC-alpha isoform throughout the human gastrointestinal tract. PKC-alpha expression was also measured and compared between normal and neoplastic colorectal tissue. PKC-alpha mRNA expression was detected in normal human gastrointestinal tract tissue using Northern blot analyses and in situ hybridization. PKC-alpha protein expression was detected in normal gastrointestinal tissue and colorectal neoplasia using Western blot and immunohistochemical analyses. PKC-alpha was expressed throughout the human gastrointestinal tract. Distinct organ and cellular localization was characterized. PKC-alpha mRNA and protein localization were most prevalent in the deep basal layer of the esophageal mucosa. In the stomach, PKC-alpha expression was detected predominately in the cells of the deep glands and surface epithelial cells but less in the mucous neck cells of the gastric pits. In the duodenum and ileum, PKC-alpha mRNA expression was greater in the deeper crypt cells than in the differentiated cells that line the villi. However, immunohistochemistry showed greater expression in the cells of the villi compared to crypt cells. In normal colonic tissue, PKC-alpha mRNA and protein predominated in the cells of the upper crypt and surface epithelial cells. PKC-alpha protein was also prominently expressed in the glands of colorectal adenocarcinoma. There was no quantitative difference in the level of PKC-alpha protein expression between normal and neoplastic colorectal tissue. The specific organ and cellular expression of PKC-alpha suggests separate and distinct functional roles for this PKC isoform throughout the gastrointestinal tissues.


[The myeloperoxidase of the polymorphonuclear leukocytes as a marker of the stage of Opisthorchis invasion and as an indicator of the efficacy of chemotherapy].
A total of 152 patients with Opisthorchis infection at the acute and chronic stage of the diseases, as well as 1-3 days and 1-2 months after therapy with biltricide in a dose of 60 mg/kg body weight. Intracellular myeloperoxidase was spectrophotometrically determined. Its activity was demonstrated to be significantly varying at the different opisthorchiasis stage. At the acute stage there was a 6-fold increase in the activity of the enzyme as compared with that at the chronic stage. The therapy resulted in the drop of myeloperoxidase levels, at the same time the authors interpret the heterodirectional changes in the activity of myeloperoxidase in the early post-therapeutic period as a fact of individual anthelmintic intolerance the normalization of the parameter studied 1 month after the therapy only in 42.1% of the cases as a fact residual Opisthorchis antigen persistence.


Modified creatine kinase-MB plots as a tool to detect perioperative myocardial infarction. Evaluation of sensitivity and specificity as compared with electrocardiographic changes.
Based on electrocardiographic criteria, coronary artery bypass grafting patients were divided into two groups, one with and one without perioperative myocardial infarction. Serial total-creatine kinase activity did not discriminate between the two groups; however, serial creatine kinase-MB activity showed a consistent difference. Patients with perioperative myocardial infarction showed an increase, whereas patients without perioperative myocardial infarction showed a decrease during the postoperative period. The creatine kinase-MB plots showed a sensitivity of 0.92 and a specificity of 0.98 as compared with the electrocardiograms.


Performing photosynthesis without β-carotene.
Research on mutant tobacco plants shows that a pigment called β-carotene is not necessary for photosynthesis.


Peripheral blood progenitor cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia.
Herein we report on the feasibility of mobilizing peripheral blood progenitor cells (PBPC) in a prospective study of the HOVON-SAKK Groups in 96 cases with newly diagnosed acute myeloid leukemia (AML). Among 96 patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with variable dosages of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. The comparative yields of pheresis following the G-CSF schedules and hematopoietic recovery data are presented and discussed. PBPC transplantation results in faster hematopoietic regeneration compared to autologous marrow grafting in the prior AML HOVON study.


Colon preneoplastic lesions in animal models.
The animal model is a powerful and fundamental tool in the field of biochemical research including toxicology, carcinogenesis, cancer therapeutics and prevention. In the carcinogenesis animal model system, numerous examples of preneoplastic lesions have been isolated and investigated from various perspectives. This may indicate that several options of endpoints to evaluate carcinogenesis effect or therapeutic outcome are presently available; however, classification of preneoplastic lesions has become complicated. For instance, these lesions include aberrant crypt foci (ACF), dysplastic ACF, flat ACF, β-catenin accumulated crypts, and mucin-depleted foci. These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments. Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions.