Aircraft passenger comfort experience: underlying factors and differentiation from discomfort.
Previous studies defined passengers' comfort based on their concerns during the flight and a set of eight experiential factors such as 'peace of mind', 'physical wellbeing', 'pleasure', etc. One Objective of this paper was to determine whether the factors underlying the passengers' experience of comfort differ from those of discomfort. Another objective was to cross-validate those factors. In the first study, respondents provided written reports of flight comfort and discomfort experiences separately and gave ratings on the impact of the eight factors on each experience. Follow up interviews were also conducted. Significant difference was found between comfort and discomfort ratings for two factors of 'pleasure', denoted by one's concern for stimulation, ambience and exceeded expectations, and 'physical wellbeing' characterized in terms of bodily support and energy. However, there were no significant differences between the comfort and discomfort ratings on the other six factors. The evidence does not support the proposition that passenger comfort and discomfort are underline by different sets of factors. It is therefore suggested that the evaluation of overall passenger comfort experience, as a whole, employ one spectrum ranging from extreme comfort to discomfort. In study two, a pool of comfort descriptors was collected. Those that were less relevant to passenger comfort were eliminated in a number of steps. Factor analysis was used to classify the remaining descriptors, using respondents' ratings on their potential impact on passenger comfort. Seven factors corresponded to the pre-determined passenger comfort factors from previous research, validating those with an exception of 'proxemics' (concerning one's privacy and control over their situation) but it was argued that this is due to the nature of the factor itself, which is context dependent and generally perceived unconsciously.


Long-term clinical outcome of helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma is comparable to that of h. pylori-positive lymphoma.
Little is still known regarding the clinical features and prognosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma without Helicobacter pylori (H. pylori) infection. From January 1996 to April 2006, a total of 185 patients with gastric MALT lymphoma were enrolled at Seoul National University Hospital. To assess the differences in clinical characteristics and long-term outcomes between H. pylori-negative (n=29, 15.7%) and H. pylori-positive (n=156, 84.3%) cases, we compared these 2 types of lymphoma. The overall median follow-up period was 39 months. There were no significant differences between the 2 groups in terms of age, macroscopic phenotype, or histologic grade. H. pylori-negative group showed male predominancy (72.4%) and higher percentage of proximal stomach location (62.1%). Although H. pylori-negative lymphomas were more frequently presented as advanced disease (stage IIE or IV, 37.9%), no significant differences in both the overall complete response and overall survival rates were observed between the 2 groups. Our results suggest that H. pylori-negative gastric MALT lymphoma shows a favorable long-term outcome, which is comparable to that of H. pylori-positive lymphoma.


Properties of acetylcholine receptors in adult rat skeletal muscle fibers in culture.
The distribution and biophysical properties of acetylcholine receptors were studied, using morphological and patch-clamp techniques, in adult rat skeletal muscle fibers dissociated by collagenase and maintained in culture. Up to ten hours after dissociation, there were no changes in either the distribution or the biophysical properties of junctional acetylcholine receptors. In long-term culture (5 to 14 days), a new type of acetylcholine receptor was inserted all over the muscle fibers; the channel properties were characterized by a longer open time and a smaller conductance, similar to what has been observed in in vivo denervated muscles. Using autoradiography, we found that during culture an impaired incorporation of new acetylcholine receptors in the former endplates caused a progressive decrease in the density of junctional acetylcholine receptors. This contrasts with muscle fibers denervated in vivo, where the density of receptors does not change after denervation.


Decreased production of specific antibodies to cow's milk proteins in premature infants during the first six months of life.
Concentrations of IgG and IgM antibodies to casein, beta-lactoglobulin, lactalbumin and bovine serum albumin (BSA) in sera of premature infants of less than 36 weeks gestation, at 5 weeks of age, were less than in age-matched term infants. At 6 months of age IgG antibodies to BSA in preterms were still significantly lower than in term infants.


Preventing Medicolegal Problems in Neurosurgical Practice: Do's and Don'ts.
There is a sea change in the scenario of medical practice, manifested in a serious trust deficit between patients and doctors and an exponential rise in malpractice litigation. This has given boost to the practice of defensive medicine by doctors. Neurosurgery is considered to be a high-risk branch of surgery in terms of potential for medicolegal issues. It is inevitable that as a response to these changes, we should identify the potential problem areas and adopt measures to deal with them. Practicing ethical, rational, and evidence-based medicine can minimize medicolegal problems. It is suggested to avoid treating patients beyond one's competence. In this review, the concept of negligence is defined, and the common allegations and causes of litigation in neurosurgical practice are identified. The importance of keeping meticulous patient records in preventing medicolegal problems is emphasized. The value of obtaining informed consent and operation-specific consent is highlighted. It is advised not to overpromise the results of treatment. The roles of effective communication and display of empathy toward treated individuals are important factors in averting litigation by them. Communication failure results in breakdown of the doctor-patient relationship. The protective value of professional liability insurance to deal with potential problems is stressed. Finally, the practice of "jousting," or bad-mouthing a colleague, is strongly condemned, as it can provoke malpractice litigation.


Identification of potent and selective inhibitors of PKR via virtual screening and traditional design.
Protein Kinase RNA-activated (PKR) inhibition is thought to be relevant for immunology due to the potential to reduce macrophage and dendritic cell responses to bacteria and its signaling downstream of TNFα. PKR is also associated with neuroscience indications such as Alzheimer's disease due to its activation by the double stranded DNA (dsDNA) virus HSV1, a virus suggested to be important in the development of AD. Studies exploring the mechanistic role of PKR with existing tool molecules such as the tricyclic oxindole C16 are clouded by the poor selectivity profile of this ATP-competitive, Type I kinase inhibitor. Type II kinase leads such as the benzothiophene or pyrazolopyrimidine scaffolds from literature are equally poor in their selectivity profiles. As such, it became necessary to identify more potent and selective chemical matter to better understand PKR biology. A dual approach was taken. The first step of the strategy included virtual screening of the AbbVie compound collection. A combination of pharmacophore-based and GPU shape-based screening was pursued to identify selective chemical matter from promiscuous leads. The second step of the strategy followed traditional compound design. This step initiated from a literature lead with PKR cross reactivity. Combined, the two parallel efforts led to identification of more selective leads for investigation of PKR biology.


Application of inferior major bone flap craniotomy decompression in brain injury.
To summarize the application of inferior major bone flap craniotomy decompression in brain injury operation. A retrospective analysis was done in 218 cases with brain injuries who were admitted to our department from January 1995 to December 1999 and treated with the inferior major bone flap craniotomy decompression. Of 218 cases, 121 cases (55.50%) were cured according to GOS, 39 (18.30%) were with good recovery or moderate disability, 13 (5.60) with severe deformity, 3 (1.40%) vegetative life, the rest 42 (19.20%) died after operation; no encephalocele or incarceration were found. The inferior major bone flap craniotomy decompression can remove hematoma timely and completely, is better than general craniotomy decompression and has a positive effect on brain injuries especially when bone flap is small.


The expression of SOCS is altered in rheumatoid arthritis.
Cytokines play a key pathogenic role in rheumatoid arthritis (RA). Several cytokines signal through the JAK-STAT pathway, which is negatively regulated by the suppressors of cytokine signalling (SOCS) proteins. Since SOCS protein levels can profoundly modulate cellular responses to cytokines, we have investigated their expression in chronic RA. The levels of SOCS1-3 and CIS1 mRNA in peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MCs), purified T cells and monocytes from RA patients and healthy volunteers were studied using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). SOCS mRNA and protein expression in synovial tissues were examined by RT-PCR and immunohistochemistry. The levels of SOCS1 and SOCS3 were significantly increased in PBMCs from RA patients when compared with healthy volunteers. These differences were mainly due to up-regulation of SOCS1 in PB T cells and of SOCS3 in PB monocytes. In addition, SOCS2 was up-regulated in PB T cells. Interestingly, SF T cells expressed lower and SF macrophages higher levels of SOCS molecules than their PB counterparts. Similarly, while a significant portion of macrophages in synovial tissues expressed SOCS1 and SOCS3 proteins, the majority of T cells remained SOCS negative. Finally, SOCS1 was up-regulated in the synovial membranes from patients with RA when compared with osteoarthritis. SOCS expression levels are profoundly altered in RA, and the profile of SOCS expression is dependent on both the cell type as well as the cellular compartment.


Vasculitis: contemporary perspectives.
Systemic vasculitis is one of the most challenging diseases for physicians from a diagnostic perspective. Clinical symptoms vary according to blood vessel size and organ systems involved. This article outlines manifestations, diagnosis, and management of the vasculitides.


Purification, characterization and primary structure of a chymotrypsin inhibitor from Naja atra venom.
A chymotrypsin inhibitor, designated NA-CI, was isolated from the venom of the Chinese cobra Naja atra by three-step chromatography. It inhibited bovine alpha-chymotrypsin with a Ki of 25 nM. The molecular mass of NA-CI was determined to be 6403.8 Da by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) analysis. The complete amino acid sequence was determined after digestion of S-carboxymethylated inhibitor with Staphylococcus aureus V8 protease and porcine trypsin. NA-CI was a single polypeptide chain composed of 57 amino acid residues. The main contact site with the protease (P1) has a Phe, showing the specificity of the inhibitor. NA-CI shared great similarity with the chymotrypsin inhibitor from Naja naja venom (identities=89.5%) and other snake venom protease inhibitors.


Muscle strength performed better than muscle mass in identifying cognitive impairment risk in maintenance hemodialysis patients.
The association between muscle mass and cognitive impairment (CI) is conflicting. We aimed to evaluate and compare the associations of muscle strength, muscle mass and CI risk in maintenance hemodialysis (MHD) patients. We conducted a multicenter, cross-sectional study. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) score. Muscle strength was assessed by hand grip strength (HGS), muscle mass was assessed by lean tissue mass (LTM). Education status was divided into two groups: lower education status (senior middle school and below) and higher education status (high school and above). Multivariable logistic regression models and subgroup analyses were performed. Receiver-operating characteristic (ROC) analyses were conducted to compare their predictive power in discriminating CI. 2827 adult MHD patients were included in our final analysis. Patients in the lowest quartile of HGS was 2.82-fold as likely to have CI as compared to those in the highest quartile, while participants in the lowest quartile of LTM group were 1.52-fold as likely to have CI, when compared with the highest quartile group of LTM after adjusting for age, gender and education level. The association persisted in all subgroups except for women and well-educated participants. There was a significant interaction between HGS and education status on CI and age played an interactive role in the association between LTM and incident CI (P for interaction < 0.05). The AUC value of the HGS was significantly higher than that of LTM (0.69 VS 0.63, P < 0.001). Muscle strength performed better than muscle mass in identifying individuals at high risk of CI, particularly in male and less educated Chinese MHD patients. Level V, cross-sectional study.


Development and application of a new in-line coupling of a miniaturized boronate affinity monolithic column with capillary zone electrophoresis for the selective enrichment and analysis of cis-diol-containing compounds.
An integrated, miniaturized and fully automated system was developed for the analysis (preconcentration/purification, separation and detection) of cis-diol containing molecules in complex matrices. This innovative in-line coupling system was achieved via the in-situ and localized synthesis of a short segment of silica-based monolith at the inlet of a 75-μm inner diameter fused silica capillary. The monolithic segment was locally functionalized with an acrylamide derivative of phenylboronic acid by free radical photopolymerization within 10min of irradiation time. Efficiency of the photopolymerization reaction was followed by frontal affinity chromatography of 1,2-dihydroxybenzene (catechol) as cis-diol model solute. An active-site amount of 0.43nmolcm-1 (9.8nmolμL-1) of phenylboronic acid moieties was obtained, with a Kd value of about 290μM close to reported value for the phenyl boronate-catechol complex. The optimal conditions of use of the miniaturized boronate affinity monolithic column (μBAMC) were determined and adapted to the in-line coupling with capillary electrophoresis. Catechol was specifically preconcentrated in a pH 8.5 phosphate buffer/MeOH (80/20, v/v) mixture. A volume up to 20 times the monolith volume can be percolated with a quantitative recovery yield. Three catecholamines were purified, preconcentrated and in-line separated. Elution from the μBAMC was performed with a small plug of acidic solution, allowing field amplified sample stacking of solutes within the plug before their in-line electrophoretic separation at pH 8.75. This unique in-line coupling was successfully used for the fully automated analysis of catecholamines neurotransmitters in urine samples, highlighting the purification efficiency of the μBAMC and the potential of such a fully integrated approach. In addition to the low sample volume required (less than 2μL), the limits of detection (LOD) accomplished with this coupling were estimated at 9.0, 9.5 and 4.8ngmL-1 for dopamine, adrenaline and noradrenaline respectively, which improves the LOD of theses solutes compared to other CE methods.


Pathophysiology of exercise dyspnea in healthy subjects and in patients with chronic obstructive pulmonary disease (COPD).
In patients with a number of cardio-respiratory disorders, breathlessness is the most common symptom limiting exercise capacity. Increased respiratory effort is frequently the chosen descriptor cluster both in normal subjects and in patients with chronic obstructive pulmonary disease (COPD) during exercise. The body of evidence indicates that dyspnea may be due to a central perception of an overall increase in central respiratory motor output directed preferentially to the rib cage muscles. On the other hand, the disparity between respiratory motor output and mechanical response of the system is also thought to play an important role in the increased perception of exercise in patients. The expiratory muscles also contribute to exercise dyspnea: a decrease in Borg scores is related to a decrease in end-expiratory lung volume and to a decrease in end-expiratory gastric pressure at isowork after lung volume reduction surgery. Changes in respiratory mechanics and intrathoracic pressure surrounding the heart can reduce cardiac output by affecting the return of blood to the heart from the periphery, or by interfering with the ability of the heart to eject blood into the peripheral circulation. Change in arterial blood gas content may affect breathlessness via direct or indirect effects. Old and more recent data have demonstrated that hypercapnia makes an independent contribution to breathlessness. In hypercapnic COPD patients an increase in PaCO2 seems to be the most important stimulus overriding all other inputs for dyspnea. Hypoxia may act indirectly by increasing ventilation (VE), and directly, independent of change in VE. Finally, chemical (metabolic) ventilatory stimuli do not have a specific effect on breathlessness other than via their stimulation of VE. We conclude that exercise provides a stimulus contributing to dyspnea, which can be applied to many diseases.


Species and susceptibility distribution of 1062 clinical yeast isolates to azoles, echinocandins, flucytosine and amphotericin B from a multi-centre study.
Descriptive values were determined for eight antifungal agents within the course of a multi-centre study encompassing 1062 German and Austrian clinical yeast isolates. Candida albicans (54%) was the predominant species isolated followed by Candida glabrata (22%), Candida parapsilosis (6%), Candida tropicalis (5.7%), Candida krusei (4.3%), as well as eleven further candidal and four non-Candida yeast species. While 519 (48.9%) isolates were tested susceptible to all antifungals tested, no isolate was found to exhibit complete cross resistance. For C. albicans, the proportions of susceptible isolates were 93.2% (amphotericin B), 95.6% (flucytosine), 84.3% (fluconazole), 83.8% (posaconazole), 91.8% (voriconazole), 96.5% (anidulafungin), 96.2% (caspofungin) and 97.6% (micafungin). Patterns of complete parallel resistances were observed within azoles (8.8%) and echinocandins (1.7%). While a decreased susceptibility was found infrequently for echinocandins and flucytosine, it was more common for azoles with highest proportions for isolates of C. glabrata (fluconazole, 40.6%; posaconazole, 37.2%), Candida guilliermondii (fluconazole and posaconazole, each 25.0%), C. krusei (posaconazole, 28.3%; voriconazole, 60%), C. parapsilosis (fluconazole, 70.3%) and C. tropicalis (fluconazole, 62.3%). The descriptive values obtained in this study represent a valid basis for the comparison of recent and future epidemiological surveys to analyse the susceptibility of yeast isolates towards major antifungal substances.


Does soil CuO nanoparticles pollution alter the gut microbiota and resistome of Enchytraeus crypticus?
Growing evidence suggests that metallic oxide nanoparticles can pose a severe risk to the health of invertebrates. Previous attention has been mostly paid to the effects of metallic oxide nanoparticles on the survival, growth and physiology of animals. In comparison, the effects on gut microbiota and incidence of antibiotic resistance genes (ARGs) in soil fauna remain poorly understood. We conducted a microcosm study to explore the responses of the non-target soil invertebrate Enchytraeus crypticus gut microbiota and resistomes to copper oxide nanoparticles (CuO NPs) and copper nitrate by using bacterial 16S rRNA gene amplicons sequencing and high throughput quantitative PCR. The results showed that exposure to Cu2+ resulted in higher bioaccumulation (P < 0.05) and lower body weight and reproduction (P < 0.05) of Enchytraeus crypticus than exposure to CuO NPs. Nevertheless, exposure to CuO NPs for 21 days markedly increased the alpha-diversity of the gut microbiota of Enchytraeus crypticus (P < 0.05) and shifted the gut microbial communities, with a significant decline in the relative abundance of the phylum Planctomycetes (from 37.26% to 19.80%, P < 0.05) and a significant elevation in the relative abundance of the phyla Bacteroidetes, Firmicutes and Acidobacteria (P < 0.05). The number of detected ARGs in the Enchytraeus crypticus gut significantly decreased from 45 in the Control treatment to 16 in the Cu(NO3)2 treatment and 20 in the CuO NPs treatment. The abundance of ARGs in the Enchytraeus crypticus gut were also significantly decreased to 38.48% when exposure to Cu(NO3)2 and 44.90% when exposure to CuO NPs (P < 0.05) compared with the controls. These results extend our understanding of the effects of metallic oxide nanoparticles on the gut microbiota and resistome of soil invertebrates.


Time course of lung injury in rat acute pancreatitis.
Lung injury is a severe complication of acute pancreatitis that increases the mortality rate of the disease. The pathophysiology of acute pancreatitis has been studied in several experimental models, but the kinetics of pulmonary complications in relation to the pancreatic disease is not completely understood. We then studied the severity of acute pancreatitis-associated lung injury over 18h in rats that had taurocholic acid injection in the pancreatic duct and determined whether blood collected from rats with pancreatitis is toxic enough to induce injury in normal lungs. Prospective, randomized, and controlled animal study in an animal research laboratory in a university hospital. We isolated lungs from rats with acute pancreatitis 2, 6, and 18h after taurocholic acid injection in the biliopancreatic duct and perfused them with blood collected from the same rats. Additionally, blood collected from rats with acute pancreatitis (time-points: 2 and 6h) was perfused in normal lungs. Taurocholic acid injection induced a severe pancreatic injury that started as early as 2h after the injection and persisted without recovery over the 18-h study period. In contrast, the pulmonary injury was transient, appearing at the 6-h time point with recovery by the end of the study. Pulmonary injury was moderate and evidenced mostly during lung reperfusion. Interestingly, blood collected at the 2-h time point in pancreatic rats induced pulmonary injury in normal lungs while blood collected at the 6-h time-point was not toxic. While pancreatic injury persists over the full experimental period, pulmonary injury is transient in our experimental model. The recovery of lung injury by 18h might be explained by a decrease in the overall toxicity of pancreatic blood over time.


Evaluation of a Saccharomyces cerevisiae Fermentation Product on the Feedlot Performance and Carcass Merit of Hair Lambs Offered an Annual Ryegrass-Hay-Based Finishing Diet: A Pilot Study.
Hair sheep production has increased in recent years, which has resulted in an increased presence in feedlots. Additionally, grass-based finishing systems for ruminant animal production have increased. Data are limited for finishing hair lambs on diets based on cool-season hay. The objective was to evaluate a Saccharomyces cerevisiae fermentation product (SCFP) on the feedlot performance and carcass characteristics of Katahdin lambs offered an annual ryegrass (Lolium multiflorum)-hay-based diet. Twenty-four Katahdin lambs (21.5 ± 2.5 kg BW) were assigned to either the control (CON) or the yeast-supplemented group (SCFP) in a completely randomized design. Lambs were offered a 14% crude protein total mixed ration diet based on annual ryegrass hay. The SCFP group also received the yeast supplement in their diet. Lambs in the SCFP group had a higher final body weight (p < 0.01) and ADG (p = 0.01). Less maximum and total energy were required to cut SCFP lamb meat compared to CON lamb meat (p < 0.03). Results from this study indicated that SCFP supplementation may prove to be beneficial in hair lamb finishing diets. Future research will need to specifically evaluate the use of these products in hair lambs with a larger sample size.


Long-term depression of two primary immune responses induced by a single dose of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC).
2 primary immune responses (anti-SRBC antibody response and allograft rejection) have been tested in mice at various time intervals after single doses of either DTIC or cyclophosphamide. The DTIC-induced immunodepression proved to be extremely long-lasting, being still detectable after 2 months.


Association between fluid overload and mortality in newborns: a systematic review and meta-analysis.
Fluid overload (FO) is associated with higher rates of mortality and morbidity in pediatric and adult populations. The aim of this systematic review and meta-analysis was to investigate the association between FO and mortality in critically ill neonates. Systematic search of Ovid MEDLINE, EMBASE, Cochrane Library, trial registries, and gray literature from inception to January 2021. We included all studies that examined neonates admitted to neonatal intensive care units and described FO and outcomes of interest. We identified 17 observational studies with a total of 4772 critically ill neonates who met the inclusion criteria. FO was associated with higher mortality (OR, 4.95 [95% CI, 2.26-10.87]), and survivors had a lower percentage of FO compared with nonsurvivors (WMD, - 4.33 [95% CI, - 8.34 to - 0.32]). Neonates who did not develop acute kidney injury (AKI) had lower FO compared with AKI patients (WMD, - 2.29 [95% CI, - 4.47 to - 0.10]). Neonates who did not require mechanical ventilation on postnatal day 7 had lower fluid balance (WMD, - 1.54 [95% CI, - 2.21 to - 0.88]). FO is associated with higher mortality, AKI, and need for mechanical ventilation in critically ill neonates in the intensive care unit. Strict control of fluid balance to prevent FO is essential. A higher resolution version of the Graphical abstract is available as Supplementary information.


Cross-conjugated poly(p-phenylene) aided supramolecular self-organization of fullerene nanocrystallites.
Formation and characterization of nanocrystallite spheres from a hybrid of functionalized cross-conjugated poly(p-phenylene) and C(60) are reported.


Hub and spoke framework for study of surgical centralization within United States health systems.
Hospital consolidation into health systems has mixed effects on surgical quality, potentially related to degree of surgical centralization at high-volume (hub) sites. We developed a novel measure of centralization and evaluated a hub and spoke framework. Surgical centralization within health systems was measured using hospital surgical volumes (American Hospital Association) and health system data (Agency for Healthcare Research and Quality). Hub and spoke hospitals were compared using mixed effects logistic regression and system characteristics associated with surgical centralization were identified using a linear model. Within 382 health systems containing 3022 hospitals, system hubs perform 63% of cases (IQR 40-84%). Hubs are larger, in metropolitan and urban areas, and more often academically affiliated. Degree of surgical centralization varies ten-fold. Larger, multistate, and investor-owned systems are less centralized. Adjusting for these factors, there is less centralization among teaching systems (p < 0.001). A hub-spoke framework applies to most health systems but centralization varies significantly. Future studies of health system surgical care should assess the contributions of surgical centralization and teaching status on differential quality.


Vasopressin modulates the activity of catecholamine containing neurons in specific brain regions.
Following the i.c.v. administration of antivasopressin serum the alpha-MPT-induced disappearance of noradrenaline was decreased in the dorsal septal nucleus, parafascicular nucleus and the rostral part of the nucleus tractus solitarii, whereas that of dopamine was lowered in the caudate nucleus and in the A2 region of the medulla oblongata. In general the effects are opposite to those previously found following the i.c.v. administration of vasopressin. The results support the hypothesis that vasopressin modulates catecholamine neurotransmission in specific brain regions of the rat.


[Expressions of COX-2 and MMP-2 in nasopharyngeal carcinoma and the their relationship with lymph node metastasis].
To study the expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) in nasopharyngeal carcinoma (NPC) and their relationship with lymph node metastasis. The expression of COX-2 and MMP-2 in 86 NPC tissues and 30 normal nasopharyngeal tissues were evaluated by immunohistochemical analysis. The positive rate of COX-2 and MMP-2 in NPC tissue was 75.58% and 66.28% respectively, which was significantly higher than that in normal nasopharyngeal (P < 0.01). The expression of both COX-2 and MMP-2 were positively correlated with lymph node metastasis (P < 0.01). There was a positive correlation between the expression of COX-2 and MMP-2 (P < 0.01). COX-2 and MMP-2 expression are increased in NPC, and they may cooperate in the course of lymph metastasis of NPC.


Parallels between cerebellum- and amygdala-dependent conditioning.
Recent evidence from cerebellum-dependent motor learning and amygdala-dependent fear conditioning indicates that, despite being mediated by different brain systems, these forms of learning might use a similar sequence of events to form new memories. In each case, learning seems to induce changes in two different groups of neurons. Changes in the first class of cells are induced very rapidly during the initial stages of learning, whereas changes in the second class of cells develop more slowly and are resistant to extinction. So, anatomically distinct cell populations might contribute differentially to the initial encoding and the long-term storage of memory in these two systems.


Pirandello's analogy: a source for a better understanding of the social impact of stroke.
Suffering a stroke has major implications for the patient. To understand human suffering, one should understand society. Pirandello described society as a higher entity than the individual, thereby justifying human adaptability to society. We explore a qualitative finding that suggests that social trends may influence how stroke patients prioritize aspects of their rehabilitation. We compare a contemporary patient's experience of stroke recovery with that of a fictional character from the works of Luigi Pirandello. Both patients had two main residual symptoms: hemiparesis and aphasia. The rehabilitation priorities of the two patients differed, and appeared to reflect the contemporaneous demands of society. Mobility was prioritized in 1910; communication was prioritized in 2010. However, essential aspects of 'being a stroke patient' remained unchanged; both patients retained a sense of self and both coped emotionally by being hopeful. We conclude that stroke patients respond to society's contemporaneous demands and expectations. Currently, society demands participation in a large social environment and this is reflected in stroke patients' priorities. This analogy could enable medical professionals to better understand the social impact of stroke, and consequently offer appropriate interventions to improve rehabilitation outcomes for individual patients.


Strain counterstrain technique to decrease tender point palpation pain compared to control conditions: a systematic review with meta-analysis.
Strain counterstrain (SCS) is an indirect osteopathic manipulative technique that uses passive positioning to relieve tender point (TP) palpation pain and associated dysfunction. The purposes of this systematic review with meta-analysis were to 1) determine the pooled effect of SCS on TP palpation pain compared to a control condition and 2) assess the quality of the overall evidence. A search conducted using the MEDLINE with AMED, PUBMED, CINAHL, and SCOPUS databases for publications from January 2002 and April 2012 yielded 29 articles for eligibility screening. Included studies were limited to randomized control trials comparing TP palpation pain after isolated SCS treatment compared to control conditions assessed with a visual analog scale. Other study designs or manipulative treatments were excluded. Two reviewers adhered to a predetermined study protocol following current Cochrane Collaboration recommendations to independently extract the data with standardized extraction forms and assess studies for methodological quality and determine risks of bias. Five randomized control trials were included for qualitative and quantitative analysis. The pooled effect of SCS was a reduction of TP palpation pain (p < 0.001, 95% CI -0.291 to -0.825). The overall evidence quality was low: while all studies met at least 8 of 12 methodological quality criteria, most were low quality. This systematic review and meta-analysis found low quality evidence suggesting that SCS may reduce TP palpation pain. Future studies with larger samples of better quality studies with patient populations that assess long-term pain, impairment, and dysfunction outcomes could enrich the literature.


Regulation of rat hepatic delta-aminolevulinic acid synthetase and heme oxygenase activities: evidence for control by heme and against mediation by prosthetic iron.
1. The effect of in vivo administration of 6 compounds on the activity of delta-aminolevulinic acid (ALA) synthetase and heme oxygenase were determined. 2. The order of decreasing potency in reducing ALA synthetase activity was heme, bilirubin, protoporphyrin IX, bilirubin dimethyl ester, CoCl2 and FeCl3. 3. The chelating agents EDTA and deferoxamine did not prevent heme's repression of ALA synthetase or induction of heme oxygenase activity. 4. The dose response, time course, enzyme subcellular distribution and chelation antagonism studies all suggest that heme itself, and not iron, regulates the rate limiting enzymatic steps of rat hepatic heme synthesis and degradation.


Aerosol particle number concentration measurements in five European cities using TSI-3022 condensation particle counter over a three-year period during health effects of air pollution on susceptible subpopulations.
In this study, long-term aerosol particle total number concentration measurements in five metropolitan areas across Europe are presented. The measurements have been carried out in Augsburg, Barcelona, Helsinki, Rome, and Stockholm using the same instrument, a condensation particle counter (TSI model 3022). The results show that in all of the studied cities, the winter concentrations are higher than the summer concentrations. In Helsinki and in Stockholm, winter concentrations are higher by a factor of two and in Augsburg almost by a factor of three compared with summer months. The winter maximum of the monthly average concentrations in these cities is between 10,000 cm(-3) and 20,000 cm(-3), whereas the summer min is approximately 5000-6000 cm(-3). In Rome and in Barcelona, the winters are more polluted compared with summers by as much as a factor of 4-10. The winter maximum in both Rome and Barcelona is close to 100,000 cm(-3), whereas the summer minimum is > 10,000 cm(-3). During the weekdays the maximum of the hourly average concentrations in all of the cities is detected during the morning hours between 7 and 10 a.m. The evening maxima were present in Barcelona, Rome, and Augsburg, but these were not as pronounced as the morning ones. The daily maxima in Helsinki and Stockholm are close or even lower than the daily minima in the more polluted cities. The concentrations between these two groups of cities are different with a factor of about five during the whole day. The study pointed out the influence of the selection of the measurement site and the configuration of the sampling line on the observed concentrations.


Discourse structure and relative clause processing.
Studies in several languages have shown that subject-relative clauses are easier to process than object-relative clauses. Mak, Vonk, and Schriefers (2006) have proposed the topichood hypothesis to account for the preference for subject-relative clauses. This hypothesis claims that the entity in the relative clause that is most topicworthy will be chosen as the subject. By default, the antecedent of the relative clause will be chosen as the subject of the relative clause, because it is the topic of the relative clause. However, when the noun phrase (NP) in the relative clause is also topicworthy, the preference for the antecedent to be the subject will disappear. This was confirmed in two experiments. In Experiment 1, we tested relative clauses with a personal pronoun in the relative clause. We obtained a preference for object-relative clauses, in line with the assumption that personal pronouns refer to a discourse topic and are thus topicworthy. In Experiment 2, the discourse status of the NP in the relative clause was manipulated; either it was not present in the preceding context, or it was the discourse topic. The experiment showed that when the NP in the relative clause refers to the discourse topic, the difficulty of object-relative clauses is reduced, in comparison with relative clauses with an NP that is new in the discourse, even in the absence of any explicit cue in the relative clause itself. The experiments show that discourse factors guide processing at the sentence level.


Chemical composition and biological activities of the Black Sea algae Polysiphonia denudata (Dillw.) Kutz. and Polysiphonia denudata f. fragilis (Sperk) Woronich.
The two investigated algae had almost identical sterol composition, but there were significant differences in the composition of the polar components and especially in the composition of the volatiles. P. denudata f. fragilis extracts possessed a stronger biological activity (antibacterial, antifungal and toxicity against Artemia salina). Despite the minute morphological differences between the two algae, we recommend P. denudata f. fragilis to be regarded as P. denudata subsp. fragilis.


Adult intussusception in Glasgow 1968-74.
A further review of adult intussusception in Glasgow between 1968 and 1974 is presented. A higher than expected incidence of idiopathic intussusception has been found both in this and in the earlier Glasgow series of Smith and Gillespie (1968)--44 per cent and 50 per cent respectively.


Psychological dysfunction accompanying subcortical dementias.
Subcortical dementia occurs both in disorders affecting the basal ganglia (for example, Parkinson's disease, Huntington's disease, and progressive supranuclear palsy) and in a variety of subcortical vascular, infectious, inflammatory, neoplastic, and traumatic conditions. The principal features of subcortical dementia include bradyphrenia, impairment of executive function, recall abnormalities, visuospatial disturbances, depression, and apathy. The syndrome contrasts with dementia of the Alzheimer type in which cortical involvement produces aphasia, combined recall and recognition deficits, and indifference. Electrophysiologic, biochemical, and metabolic studies support a distinction between subcortical and cortical dementias.


Current Update on Desmoid Fibromatosis.
The purpose of this article is to review the etiopathogenesis, molecular cytogenetics, histopathology, clinical features, and multimodality imaging features of desmoid fibromatosis. Recent advances in the management of desmoid fibromatosis will also be discussed. Desmoid fibromatosis is a rare soft tissue neoplasm with a high incidence of local recurrence. Imaging plays an important role in the diagnosis and management of this disease.


Establishment of a new human myeloma cell line (U-2030) and selection of a hat-sensitive subline.
We have established a new human myeloma cell line from the pleural effusion of a patient with an IgA lambda myeloma, using special tissue culture conditions and selection procedures to prevent the outgrowth of contaminating Epstein-Barr virus (EBV)-carrying normal B-lymphoblastoid cells present in the explant. The myeloma cell line, U-2030, is aneuploid and EBNA-negative and has morphological features, reactivity with cytochemical markers and cell-surface antigen expression typical of plasmablasts. The cell line thus appears to be representative of the malignant clone in vivo. However, functionally the line is a non-Ig-producer and must therefore be derived from a non-secretory variant cell present within the highly aneuploid myeloma cell clone in vivo. The U-2030 differs from previously established human myeloma cell lines in that it has a comparatively high growth rate, is clonable and can be made HAT-sensitive relatively easily. This, together with the facts that it is a non-Ig-producer and mycoplasma-free, suggests that the 6-thioguanine-resistant, HAT-sensitive subline, U-2030 TG, derived from this cell line may be used as a malignant fusion partner for the production of human-human hybridomas. An EBV-carrying lymphoblastoid cell line (U-2031) was also established. This line was diploid and had all the phenotypic properties of lymphoblastoid lines established from normal individuals.


A human GRPr-transfected Ace-1 canine prostate cancer model in mice.
A versatile drug screening system was developed to simplify early targeted drug discovery in mice and then translate readily from mice to a dog prostate cancer model that more fully replicates the features of human prostate cancer. We stably transfected human cDNA of the GRPr bombesin (BBN) receptor subtype to canine Ace-1 prostate cancer cells (Ace-1(huGRPr) ). Expression was examined by (125) I-Tyr(4) -BBN competition, calcium stimulation assay, and fluorescent microscopy. A dual tumor nude mouse xenograft model was developed from Ace-1(CMV) (vector transfected Ace-1) and Ace-1(huGRPr) cells. The model was used to explore the in vivo behavior of two new IRDye800-labeled GRPr binding optical imaging agents: 800-G-Abz4-t-BBN, from a GRPr agonist peptide, and 800-G-Abz4-STAT, from a GRPr antagonist peptide, by imaging the tumor mice and dissected organs. Both agents bound Ace-1(huGRPr) and PC-3, a known GRPr-expressing human prostate cancer cell line, with 4-13 nM IC50 against (125) I-Tyr(4) -BBN, but did not bind Ace-1(CMV) cells (vector transfected). Binding was blocked by bombesin. Ca(2+) activation assays demonstrated that Ace-1(huGPRr) expressed biologically active GRPr. Both Ace-1 cell lines grew in the flanks of 100% of the nude mice and formed tumors of ∼0.5 cm diameter in 1 week. In vivo imaging of the mice at 800 nm emission showed GRPr+: GRPr- tumor signal brighter by a factor of two at 24 h post IV administration of 10 nmol of the imaging agents. Blood retention (4-8% ID at 1 h) was greater by a factor >10 and cumulative urine accumulation (28-30% at 4 h) was less by a factor 2 compared to a radioactive analog of the t-BBN containing agent, (177) LuAMBA, probably due to binding to blood albumin, which we confirmed in a mouse serum assay. The dual tumor Ace-1(CMV) /Ace-1(huGRPr) model system provides a rapid test of specific to nonspecific binding of new GRPr avid agents in a model that will extend logically to the known Ace-1 orthotopic canine prostate cancer model. Prostate 76:783-795, 2016. © 2016 Wiley Periodicals, Inc.


[Unusual self mutilation with the purpose of obtaining illegal insurance benefits].
In this unusual form of self mutilation the fracture of the phalanx has been carried out--upon request--by foreign person (inderect self mutilation), in order to obtain illegal accident insurance money. Short survey of the relevant literature is given and the possibilities are outlined, which facilitate at the primary wound dressing the establishment of suspicious cases.


Visualizing sexual assault: an exploration of the use of optical technologies in the medico-legal context.
This article is an exploration of the visualization of sexual assault in the context of adult women. In investigating the production of visual evidence, we outline the evolution of the specialized knowledge of medico-legal experts and describe the optical technologies involved in medical forensic examinations. We theorize that the principles and practices characterizing medicine, science and the law are mirrored in the medico-legal response to sexual assault. More specifically, we suggest that the demand for visual proof underpins the positivist approach taken in the pursuit of legal truth and that the generation of such evidence is based on producing discrete and decontextualized empirical facts through what are perceived to be objective technologies. Drawing on interview and focus group data with 14 sexual assault nurse examiners (SANEs) in Ontario, Canada, we examine perceptions and experiences of the role of the visual in sexual assault. Certain of their comments appear to lend support to our theoretical assumptions, indicating a sense of the institutional overemphasis placed on physical damage to sexually assaulted women's bodies and the drive towards the increased technologization of visual evidence documentation. They also noted that physical injuries are frequently absent and that those observed through more refined tools of microvisualization such as colposcopes may be explained away as having resulted from either vigorous consensual sex or a "trivial" sexual assault. Concerns were expressed regarding the possibly problematic ways in which either the lack or particular nature of visual evidence may play out in the legal context. The process of documenting external and internal injuries created for some an uncomfortable sense of fragmenting and objectifying the bodies of those women they must simultaneously care for. We point to the need for further research to enhance our understanding of this issue.


The caregiver's perception of behavioral disturbance in relatives with schizophrenia: a stress-coping approach.
This article suggests some theoretical orientations in studying behavioral disturbance from a stress-coping perspective. First, an overview of Lazarus and Folkman's cognitive theory of stress is presented. Secondly, some linkages are proposed between the rating scales used to measure behavioral disturbance and the concepts of this theory. Future research directions are then suggested to further explore the affective, cognitive and behavioral responses related to the management of disturbing behaviors.


Brain Mitochondrial Subproteome of Rpn10-Binding Proteins and Its Changes Induced by the Neurotoxin MPTP and the Neuroprotector Isatin.
Mitochondria play an important role in molecular mechanisms of neuroplasticity, adaptive changes of the brain that occur in the structure and function of its cells in response to altered physiological conditions or development of pathological disorders. Mitochondria are a crucial target for actions of neurotoxins, causing symptoms of Parkinson's disease in various experimental animal models, and also neuroprotectors. Good evidence exists in the literature that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria), and neuroprotective effects of certain antiparkinsonian agents (monoamine oxidase inhibitors) may be associated with their effects on UPS. The 19S proteasomal Rpn10 subunit is considered as a ubiquitin receptor responsible for delivery of ubiquitinated proteins to the proteasome proteolytic machinery. In this study, we investigated proteomic profiles of mouse brain mitochondrial Rpn10-binding proteins, brain monoamine oxidase B (MAO B) activity, and their changes induced by a single-dose administration of the neurotoxin MPTP and the neuroprotector isatin. Administration of isatin to mice prevented MPTP-induced inactivation of MAO B and influenced the profile of brain mitochondrial Rpn10-binding proteins, in which two pools of proteins were clearly recognized. The constitutive pool was insensitive to neurotoxic/neuroprotective treatments, while the variable pool was specifically influenced by MPTP and the neuroprotector isatin. Taking into consideration that the neuroprotective dose of isatin used in this study can result in brain isatin concentrations that are proapoptotic for cells in vitro, the altered repertoire of mitochondrial Rpn10-binding proteins may thus represent a part of a switch mechanism from targeted elimination of individual (damaged) proteins to more efficient ("global") elimination of damaged organelles and whole damaged cells.


Chemical bioactive profile of mountain celery as affected by vegetative stages.
Mountain celery (MC) is an endemic plant native to Iran. The plant possesses several nutritional and industrial applications bestowed by a wide range of bioactive compounds. The present study investigated some changes in the chemical composition of fresh arial parts of MC at different vegetative stages. The headspace (HS) technique in tandem with GC-MS analysis were implemented to identify bioactive compounds. Results indicated that phthalides, sesquiterpenes, and monoterpenes were the main constituents in MC. It was found that MC had higher concentration and more diverse composition of phthalides at younger age. It seems MC farming has the potential to be commercialized with a decent revenue.


Preventing COVID-19 with Chinese Medicine: Concepts and Suggestions.
The category of "epidemic diseases" is discussed extensively in the literature of traditional Chinese medicine, however it is often overlooked in modern Chinese medicine education precisely because population-level prevention and treatment do not fit easily into the dogma that individualized herbal formulas "based on patterns identified" is the primary mode of clinical reasoning in Chinese medicine. In the recent COVID-19 epidemic, the contingencies of treating large numbers of patients meant that it was not possible to provide "one prescription for each patient." In fact, four categories of patients were sometimes given the same formula: mild and moderate confirmed cases, close contacts of confirmed cases, and suspected cases. The lines between prevention and treatment, along with clear demarcations between individual and population-level immunity, were blurred in the mist of the urgent imperative to provide what could reasonably be expected to be effective. Lessons from the large-scale participation of Chinese medicine in the COVID-19 public health crisis are relevant for the global community of Chinese medicine practitioners and may provide insights into how future epidemics could be addressed in the absence of effective vaccines or pharmaceuticals.


Educating the Colleagues: Radiation Basics for Obstetrics and Gynecology Residents.
Exposure to radiation oncology (RO) is limited among medical students, excluding those who wish to pursue a radiation oncology career. Consequently, RO knowledge in gynecological malignancies may differ among obstetricians and gynecologists (OB&G), depending on their experience and training level. Establishing a program to educate OB&G residents about basic radiation oncology principles may improve patients' coordination and treatment with gynecological malignancies. At our institution, radiation oncology residents conducted a 2-part training session for OB&G colleagues, which included a lecture and hands-on training. Educational sessions targeting OB&G residents are needed to enhance knowledge about radiation treatments and improve patient care.


Neuronal cell type-specific promoter of the alpha CaM kinase II gene is activated by Zic2, a Zic family zinc finger protein.
To understand the neuronal cell type-specific expression of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), we investigated binding proteins that specifically activated the promoter of the alpha isoform of CaM kinase II (alpha CaM kinase II). Proteins that bind the promoter sequence were found in rat brain nuclear extract by electrophoretic mobility shift assay. Then, we screened for binding proteins in a mouse brain cDNA library using the yeast one-hybrid system. Zic2, a Zic family zinc finger transcription factor, was identified as one of the binding proteins. To investigate the effect of Zic2 on the promoter activity, Zic2 cDNA was expressed with a luciferase reporter gene containing a neuronal cell type-specific promoter of alpha CaM kinase II in neuronal and non-neuronal cells. The promoter activity of alpha CaM kinase II was enhanced 1.3-5-fold in cultured neuronal cells by Zic2. The activation was varied among neuronal cell types. Zic2 also increased the promoter activity in non-neuronal cells, although the relative luciferase activites in non-neuronal cells were lower than those in neuronal cell lines. These results indicated that Zic2 was one of the proteins binding to, and regulating the activity of, the promoter of alpha CaM kinase II.


Iron phthalocyanine with coordination induced electronic localization to boost oxygen reduction reaction.
Iron phthalocyanine (FePc) is a promising non-precious catalyst for the oxygen reduction reaction (ORR). Unfortunately, FePc with plane-symmetric FeN4 site usually exhibits an unsatisfactory ORR activity due to its poor O2 adsorption and activation. Here, we report an axial Fe-O coordination induced electronic localization strategy to improve its O2 adsorption, activation and thus the ORR performance. Theoretical calculations indicate that the Fe-O coordination evokes the electronic localization among the axial direction of O-FeN4 sites to enhance O2 adsorption and activation. To realize this speculation, FePc is coordinated with an oxidized carbon. Synchrotron X-ray absorption and Mössbauer spectra validate Fe-O coordination between FePc and carbon. The obtained catalyst exhibits fast kinetics for O2 adsorption and activation with an ultralow Tafel slope of 27.5 mV dec-1 and a remarkable half-wave potential of 0.90 V. This work offers a new strategy to regulate catalytic sites for better performance.


The preparation and determination of structure of benzylpenicilloyl compounds used in skin-testing for penicillin allergy.
The preparation of alpha-D-benzylpenicilloyl-n-propylamine and octa-epsilon-(alpha-D-benzylpenicilloyl)-octa-alpha-L-lysine are described. Their structures were established by chemical and spectroscopic evidence. Proton and carbon-13 nuclear magnetic resonance spectra of these two penicillin derivatives and some related compounds are provided. These compounds are useful in skin testing for penicillin allergy.


Prediction of Human Pharmacokinetic Profile After Transdermal Drug Application Using Excised Human Skin.
Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited. Therefore, the aim of this study is to investigate the prediction of human plasma concentrations after dermal application using in vitro permeation parameters obtained from excised human skin. The in vitro skin permeability of 7 marketed drug products was evaluated. The plasma concentration-time profiles of the drug substances in humans after their dermal application were simulated using compartment models and the clinical pharmacokinetic parameters. The transdermal process was simulated using the in vitro skin permeation rate and lag time assuming a zero-order absorption. These simulated plasma concentration profiles were compared with the clinical data. The result revealed that the steady-state plasma concentration of diclofenac and the maximum concentrations of nicotine, bisoprolol, rivastigmine, and lidocaine after topical application were within 2-fold of the clinical data. Furthermore, the simulated concentration profiles of bisoprolol, nicotine, and rivastigmine reproduced the decrease in absorption due to drug depletion from the formulation. In conclusion, this simple compartment model using in vitro human skin permeation parameters as zero-order absorption predicted the human plasma concentrations accurately.


The last-born daughter cell contributes to division orientation of Drosophila larval neuroblasts.
Controlling the orientation of cell division is important in the context of cell fate choices and tissue morphogenesis. However, the mechanisms providing the required positional information remain incompletely understood. Here we use stem cells of the Drosophila larval brain that stably maintain their axis of polarity and division between cell cycles to identify cues that orient cell division. Using live cell imaging of cultured brains, laser ablation and genetics, we reveal that division axis maintenance relies on their last-born daughter cell. We propose that, in addition to known intrinsic cues, stem cells in the developing fly brain are polarized by an extrinsic signal. We further find that division axis maintenance allows neuroblasts to maximize their contact area with glial cells known to provide protective and proliferative signals to neuroblasts.


Halogen bonding interactions in the XC5H4N···YCF3 (X = CH3, H, Cl, CN, NO2; Y = Cl, Br, I) complexes.
The noncovalent interactions between the σ-hole region outside the halogen atom and the nitrogen atom of pyridine and its para-substituted derivatives are the focus of this work. Based on the analyses of the electrostatic potentials, YCF3 (Y = Cl, Br, I) act as halogen bond donors, XC5H4N (X = CH3, H, Cl, CN, NO2) act as halogen bond acceptors, and the binary halogen-bonded complexes XC5H4N···YCF3 have been designed and investigated by B3LYP-D3/aug-cc-pVDZ calculations together with the aug-cc-pVDZ-PP basis set for iodine. When the halogen bond acceptor remains unchanged, the interactions between C5H5N and YCF3 (Y = Cl, Br, I) increase with the order of Y = Cl, Br, and I. When the halogen donor ICF3 is fixed, the halogen bonding interactions decrease along the sequence of X = CH3, H, Cl, CN, NO2. Therefore, the halogen bond of the CH3C5H4N···ICF3 complex is the strongest. The interactions between Lewis acid YCF3 (Y = Cl, Br, I) and pyridine and para-substituted pyridine are closed-shell and noncovalent interactions. On the one hand, when the halogen bond acceptor XC5H4N is fixed, with the increase of halogen atomic number, the strength of halogen bond increases; on the other hand, when the halogen bond donor ICF3 is fixed, as the electron-withdrawing ability of the electron-withdrawing group (X) increases, the halogen bond gradually weakens.


Neutrophil metabolism in the cancer context.
Neutrophils are critical innate immune cells for the host anti-bacterial defense. Throughout their lifecycle, neutrophils are exposed to different microenvironments and modulate their metabolism to survive and sustain their functions. Although tumor cell metabolism has been intensively investigated, how neutrophil metabolism is affected in cancer remains largely to be discovered. Neutrophils are described as mainly glycolytic cells. However, distinct tumor-associated neutrophil (TAN) states may co-exist in tumors and adapt their metabolism to exert different or even opposing activities ranging from tumor cell killing to tumor support. In this review, we gather evidence about the metabolic mechanisms that underly TANs' pro- or anti-tumoral functions in cancer. We first discuss how tumor-secreted factors and the heterogenous tumor microenvironment can have a strong impact on TAN metabolism. We then describe alternative metabolic pathways used by TANs to exert their functions in cancer, from basic glycolysis to more recently-recognized but less understood metabolic shifts toward mitochondrial oxidative metabolism, lipid and amino acid metabolism and even autophagy. Last, we discuss promising strategies targeting neutrophil metabolism to combat cancer.


Genetic variation in restriction patterns among mouse amylase gene complexes.
The expression of pancreatic amylase in the mouse exhibits pronounced genetic variation. Congenic lines with various amylase complexes on a common C3H/As background have different numbers and forms of isoenzymes. The relative ratio of these isoenzymes may vary, as does the overall production of pancreatic amylase, which in some lines is three- to fourfold higher than in others. DNA from a number of lines was digested with endonucleases and hybridized to an amylase cDNA probe. The restriction patterns from inbred stocks and the corresponding congenic lines are identical, demonstrating that the majority of (if not all) amylase-like DNA sequences is found within the amylase complex. Congenic lines with specific amylase expression, for instance, in enzyme production, show different restriction patterns, whereas three lines with the same amylase phenotype have a uniform pattern. Most of the variation in amylase expression is represented among congenic lines derived from Danish mice. A comparison of such lines with others of remote geographic origin reveals that the restriction patterns of the "Danish" lines have by far the highest degree of resemblance. This observation seems to exclude major rearrangements within the amylase complex as the cause of the differences in enzyme expression, which instead are likely to be due to variation in regulatory elements associated with the active structural amylase genes in the complex.


Intra-abdominal splenosis: how clinical history and imaging features averted an invasive procedure for tissue diagnosis.
A 47-year-old man with a past history of splenectomy was referred for biopsy of a liver lesion. A subsequent (99m)technetium heat-damaged red cell scan helped make the diagnosis of splenosis and averted a biopsy procedure.


Sex differences in Parkinson's disease presentation and progression.
Females have a reduced risk of Parkinson's disease (PD). However, it is unclear if sex is a prognostic factor. We aimed to examine differences in presentation, physician- and patient-reported PD outcomes, and progression by sex in a large clinical cohort. This study was a secondary analysis of a cohort of PD patients seen at a tertiary care center. Sociodemographic and clinical characteristics, treatment, care timing, and outcomes were examined by sex. Sex differences in progression of impairment, disability, and health-related quality of life (HRQoL) were tested with five-year piecewise linear mixed-effects models. A mediation analysis assessed drivers of sex differences. The study included 914 males and 549 females. Females had significantly less social support, more psychological distress, and worse self-reported (but not physician-reported) disability and HRQoL at initial PD care visits, compared to males. Addressing anxiety symptoms may attenuate this difference. PD progression sex differences were minimal. PD progression does not differ by sex, yet patient-reported measures of disease severity are worse in females than males. To attenuate this sex difference in disease experience, psychological distress screening and management, particularly targeting females, should be implemented as part of PD clinical care.


Replacing the cyclohexene-linker of FR181157 leading to novel IP receptor agonists: orally active prostacyclin mimetics. Part 6.
The synthesis and biological activity of novel derivatives of our previously reported IP receptor agonist FR181157 is described. SAR studies to replace the cyclohexene-linker of FR181157 led to the discovery of compound 1i (FR207845) as a potent non-prostanoid PGI2 mimetic with good oral bioavailability.


Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells.
Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.


p-Cresol and Cardiovascular Risk in Kidney Transplant Recipients.
p-Cresol Sulphate (pCS) is a uremic toxin that originates exclusively from dietary sources and has a high plasma level related to chronic kidney disease (CKD) and cardiovascular disease (CVD). The aim of our study was to evaluate the plasma levels of pCS in kidney transplant recipients (KTRs) related to estimated glomerular filtration rate (eGFR), traditional risk factors, cardiovascular clinical events and endothelial progenitor cells (EPCs), bone marrow-derived cells for the vascular repair system. We considered 51 KTRs and 25 healthy blood donors (HBDs). pCs levels were analyzed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry with an electrospray ionization (ESI) (LC/ESI-MS/MS) on a triple-quadrupole; EPCs were analyzed using flow cytometric analysis. eGFR was 52.61 ± 19.9 mL/min/1.73 m(2) in KTRs versus 94 ± 21 mL/min/1.73 m(2) in HBDs. We did not find differences in pCS levels between KTRs and HBDs. Levels of pCS were inversely related with eGFR in KTRs and pCS levels were significantly lower in KTRs with eGFR <30 mL/min/1.73 m(2) versus eGFR >30 mL/min/1.73 m(2). Furthermore, there was a difference in pCS levels between eGFR <30 mL/min/1.73 m(2) of KTRs compared with HBDs. Levels of pCS were almost significantly influenced by the presence of a previous vascular event and were inversely related with mature EPCs. These findings suggest that KTRs should not have higher CVD risk than HBDs and their physiological vascular repair system appears to be intact. In KTRs the reduction of eGFR also increased pCS levels and reduced EPCs numbers and angiogenesis capacity. In summary, pCS acts as an emerging marker of a uremic state, helping assess the global vascular competence in KTRs.


[Image-guided adaptive brachytherapy in the treatment of patients with cervix cancer].
Deep modifications have occurred these last years in the brachytherapy use in patients with cervix cancer. Imaging allowed a more precise definition of the volumes of interest linked to the tumour and its extension as well as a better visualization of organs at risk. Recommendations on delineation modalities were published in 2005, leading to definition homogeneity, even if large variations are still observed among centres, in terms of techniques and doses. These new definitions also served as basis for new applicators development, allowing a combination of interstitial and endocavitary techniques. Results from centres using image-guided brachytherapy (MRI in particular) evidenced local control improvement, without increase in complications. Retrospective and prospective studies are currently under evaluation. These studies will likely be able to determine dose required to sterilize tumours, as a function of stage and size, as well as dose limits for organs at risk.


MicroRNA-204 suppresses epileptiform discharges through regulating TrkB-ERK1/2-CREB signaling in cultured hippocampal neurons.
MicroRNAs (miRs) have been increasingly recognized as post-transcriptional regulators involved in the pathogenesis of epilepsy. Extensive evidence suggests that inhibition of tropomyosin related kinase type B (TrkB) signaling limits epileptogenesis. It has been reported that miR-204 directly targeted and downregulated TrkB protein in a variety of cancers to suppress tumorigenesis, but its effect on epileptogenesis is unknown. Here we showed that miR-204 was downregulated in cultured hippocampal neurons following status epilepticus (SE) induced by Mg(2+)-free treatment. Overexpression of miR-204 using a transfection technique negatively regulated the expression of TrkB mRNA. Insight into the downstream signaling pathway activated by TrkB may provide valuable clues to the underlying mechanisms of epileptogenesis. Biochemical measures revealed activation of phospholipase Cγ1 (PLCγ1), extracellular signal-regulated kinase1/2 (ERK1/2) and cAMP response-element binding protein (CREB) signaling molecules in the Mg(2+)-free model in hippocampal neurons, of which ERK1/2-CREB but not PLCγ1 signaling pathway was able to be inhibited by miR-204. Epileptiform discharges assessed using whole-cell current-clamp techniques were suppressed by miR-204 in cultured hippocampus neurons of SE. These results suggest that miR-204 exerts an antiepileptogenic effect in the Mg(2+)-free model in hippocampal neurons through regulating TrkB and downstream ERK1/2-CREB signaling pathway.


Pesticides exposure in Culturama, Brazil--knowledge, attitudes, and practices.
In this study, the knowledge, attitudes, and practices associated with pesticide use and exposure were evaluated in the agricultural community of Culturama, in the state of Mato Grosso do Sul, Brazil. A standardized questionnaire was completed by 250 farm workers aged > or =18 years old. The average age of the studied population was 43.6 years and 17.6% had never been to school. Their farms were small (approximately 30ha) and family operated and did not utilize advanced farming technology. About 92% of the interviewees had worked directly with pesticides and 59.6% reported typical intoxication symptoms. Only 44.3%, however, believe that they had been intoxicated. A significant correlation was found between hand washing after pesticide application and reporting symptoms (P=0.014). Over 90% of the farmers reported using the organophosphorus insecticide methamidophos. A great majority (>90%) considered pesticides to be harmful to human health, but less than 20% used masks, impermeable clothes, or gloves during pesticide application. These results indicate that special educational programs, legislation promoting the use of safer pesticides, and implementation of personal protective measures are necessary to decrease the pesticide exposure of farmers in Culturama.


Host risk factors for the development of multiple non-melanoma skin cancers.
Non-melanoma skin cancer (NMSC) is the most common cancer in the US, and having multiple lesions conveys substantial cost and morbidity for the individual involved. Although there are data available on risk factors for NMSC, there are currently few studies that identify specific risk factors for development of multiple NMSCs. We evaluated host risk factors for multiple NMSCs among men (Health Professionals Follow-up Study) and women (Nurses' Health Study). Compared with individuals with a single NMSC, having greater number of sunburns was a risk factor for developing ≥ 2 NMSCs [≥ 10 sunburns, cumulative relative risk (RR) = 1.21, 95% confidence interval (CI): 1.07-1.36] and a higher risk of developing ≥ 11 NMSCs (≥10 sunburns, RR = 2.33, 95% CI: 1.57-3.46). Inability-to-tan was associated with risk of developing ≥ 2 NMSCs (cumulative RR = 1.29, 95% CI: 1.18-1.40) and a higher risk of developing ≥ 11 NMSCs (RR = 1.91, 95% CI: 1.50-2.43). Men had an increased risk of developing ≥ 2 NMSCs (cumulative RR = 1.53, 95% CI: 1.40-1.66). Risk of developing 2-4, 5-10 and ≥11 NMSCs increased with age. Other risk factors for developing ≥ 2 NMSCs included red natural hair colour (cumulative RR = 1.23, 95% CI: 1.07-1.42), family history of melanoma (cumulative RR = 1.15, 95% CI: 1.03-1.28), and having ≥ 6 nevi on the left arm (cumulative RR = 1.22, 95% CI: 1.07-1.40). In conclusion, physicians caring for individuals with incident NMSCs may consider paying special attention to those at highest risk for developing additional tumours, especially males and those with a history of ≥ 10 lifetime sunburns, by performing routine full skin examinations and counselling for aggressive photoprotection.


[Microsporum canis: Current data on the prevalence of the zoophilic dermatophyte in central Germany].
Microsporum (M.) canis, whose source of infection is mostly cats, is still considered as the most frequently occurring zoophilic dermatophyte in Germany and Europe. In distinct areas of Germany, the zoophilic dermatophyte Trichophyton (T.) anamorph of Arthroderma (A.) benhamiae also presents a frequent and emerging causative agent of dermatophytoses. Over a period of 3 years, from March 2010 to March 2013, skin samples from scalp, face, trunk, and limbs were investigated using mycological cultivation and by polymerase chain reaction (PCR) for dermatophytes. Materials originated in particular from the German Free States Saxony and Thuringia, and from the Federal State Saxony-Anhalt, but also included samples submitted from around Germany. The cultural detection of dermatophytes was performed on Sabouraud's 4% glucose agar with and without cycloheximide. For dermatophyte DNA detection, a uniplex PCR-ELISA was used. In all, 8464 samples from a total of 7680 patients were investigated. In 114 (1.5%) of 7680 patients, M. canis could be detected both by culture and/or PCR. M. canis was detected culturally in 100 samples, in 107 samples by PCR, in 91 samples both culturally and by PCR. For 12 patients, only cultural detection was done (without PCR). Also detected was tinea corporis due to M. canis in 59 patients, tinea capitis 8, tinea faciei 5, and tinea manus 2 patients. Of the patients, 45% were younger than 20 years, 42% were 20-49 years old, and 13% were 50 years or older. In comparison, T. anamorph of A. benhamiae was detectable by culture and/or PCR in 231 of 7680 patients (2.9%). M. canis was the second most common zoophilic dermatophyte. M. canis is still a frequent zoophilic dermatophyte in Germany. Since a few years ago, a rise of infections due to T. anamorph of A. benhamiae has been observed in Germany and other European countries. At least in distinct regions of Germany, this zoophilic dermatophyte, which is transferred from guinea pigs to human beings, currently seems to be more frequent when compared to M. canis.


Effects of the Fab fragment of digoxin antibody on the natriuresis and increase in blood pressure induced by intracerebroventricular infusion of hypertonic saline solution in rats.
1. The effects of intravenous injection of Fab fragments of anti-digoxin IgG (Digibind) on the changes in blood pressure, urine volume and urinary sodium excretion after intracerebroventricular infusion of artificial cerebrospinal fluid with normal or high sodium concentration were examined in anaesthetized rats. 2. The biological efficacy of Digibind was confirmed by experiments in vitro and in vivo, which showed that pretreatment with Digibind completely abolished or significantly attenuated the aortic contractile response or pressor response to digoxin in guinea-pigs. 3. Infusion of high-sodium cerebrospinal fluid, but not normal-sodium cerebrospinal fluid, into the lateral brain ventricle of rats caused marked increases in blood pressure, urine volume and urinary sodium excretion. 4. Digibind did not significantly affect the increases in blood pressure, urine volume and urinary sodium excretion caused by intracerebroventricular infusion of high-sodium cerebrospinal fluid. 5. Digoxin-like immunoreactive factor may play a minor role, if any, in central nervous system-induced natriuresis in rats.


Survival analysis of factors affecting the timing of COVID-19 non-pharmaceutical interventions by U.S. universities.
During March of 2020 the Centers for Disease Control and Prevention (CDC) announced non-pharmaceutical intervention (NPI) guidance as the primary mitigation strategy against growing COVID-19 community spread due to the absence of a vaccine or effective treatment at that time. CDC guidance states that NPIs are most effective when instituted in an early, targeted, and layered fashion. NPIs are effective in slowing spread, and measures should be custom-tailored to each population. This study examines factors associated with implementation and timing of NPI interventions across large public and private U.S. universities at the onset of the COVID-19 pandemic. NPI decisions of interest include when U.S. universities canceled international travel, shifted to online learning, moved faculty/staff to remote work, limited campus housing, and closed campus for all non-essential personnel. Cox proportional hazard analyses of retrospective data were conducted to assess the time to NPI events. Hazard ratios were calculated for university governance, campus setting, religious affiliation, health infrastructure, faculty diversity, and student demographics. The methods control for variance inflation factors, COVID case prevalence, and time varying covariates of spring break and states' state of emergency (SOE) orders. This study captures NPI decisions at 575 U.S. universities during spring of 2020 which affected the movement of seven million students and two million employees. Universities located in districts represented by Democratic party congressional members reported earlier NPI implementation than Republican (Cox proportional hazard ratio (HR) range 0.61-0.80). University religious affiliation was not associated with the timing any of the NPI decisions. Universities with more diverse faculty showed an association with earlier NPI implementation (HR range 0.65-0.76). The existence of university-affiliated health infrastructure was not associated with NPI timing. University NPI implementation was largely driven by local COVID-19 epidemiology, culture and political concerns. The timing of university NPI decisions varied by regional politics, faculty demographics, university governance, campus setting, and foreign student prevalence adjusting for COVID-19 state case prevalence and spring break timing. Religious affiliation and presence of university health infrastructure were not associated with timing.


Multifrequency nonlinear model of magnetic material with artificial intelligence optimization.
Magnetic rings are extensively used in power products where they often operate in high frequency and high current conditions, such as for mitigation of excessive voltages in high-power switchgear equipment. We provide a general model of a magnetic ring that reproduces both frequency and current dependencies with the use of artificial intelligence (AI) optimization methods. The model has a form of a lumped element equivalent circuit that is suitable for power system transient studies. A previously published conventional (non-AI) model, which we take as a starting point, gives a good fit of parameters but uneven characteristics as a function of current, which pose numerical instabilities in transient simulations. We first enforce the Langevin function relationship to obtain smooth characteristics of parameters, which reduces the number of parameters and ensures their even characteristics, however, compromises fit quality. We then use AI metaheuristic optimization methods that give a perfect fit for the model in the whole range of frequency up to 100 MHz and current up to saturation, with smooth characteristics of its parameters. Additionally, for such fitted parameters, we show that it is feasible to find a frequency dependence for the magnetic saturation parameter of the Jiles-Atherton (JA) model, thus enabling frequency-dependent JA.


Does increased pulmonary blood flow redistribute towards edematous lung units?
Unilobar pulmonary edema secondary to increased capillary permeability was produced utilizing oleic acid infusion into the left lower lobe pulmonary artery of seven dogs. This model was used to determine whether random changes in cardiac output produced by opening and closing arteriovenous fistulae were associated with changes in fractional perfusion to the edematous lobe (as determined by differentially labeled radiomicrospheres) thus explaining changes in intrapulmonary shunt. With an increase in cardiac output from a mean (+/- SD) of 1.6 +/- 0.5 liters/min to 2.6 +/- 0.8 liters/min (P less than 0.01), mean (+/- SD) injured lobar shunt as measured from O2 contents of lower lobar pulmonary venous blood and mixed venous blood increased from 54.4 +/- 3.0% to 74.4 +/- 22.1% while total intrapulmonary shunt increased from 12.0 +/- 4.0% to 16.0 +/- 3.7% (P less than 0.01). This increase in intrapulmonary shunt was, however, not associated with preferential perfusion of the edematous lobe, the mean (+/- SD) of the perfusion to the edematous lobe expressed as a percentage of the cardiac output being 16.6 +/- 1.6% at the low cardiac output and 16.9 +/- 1.4% at the high cardiac output. It is concluded that redistribution of blood flow towards the edematous lobe does not occur with increases in cardiac output and therefore does not account for the increased intrapulmonary shunt.


The complete genome sequence of a bile-isolated Stenotrophomonas maltophilia ZT1.
Stenotrophomonas maltophilia is one of the most frequently isolated opportunistic pathogens that can cause infections in humans. Many researches concerned the mechanism of antibiotic resistance displayed by S. maltophilia, however, the mechanism of its pathogenesis and its adaptation to special niches, such as bile, remain unclear. In this study, the S. maltophilia strain ZT1 was isolated from human bile. Its genome was sequenced and a circular chromosome of 4,391,471 bp was obtained with a GC content of 66.51%. There were 3962 protein-coding sequences, 7 rRNAs and 74 tRNAs in the chromosome. Compared with Virulence Factor Database, we identified more than 500 candidate virulence genes including genes encoding fimbrial assembly protein, enterobactin synthesis pathway proteins, efflux pumps, and the DNA and/or proteins secretion system in the genome of strain ZT1. Additionally, there were at least 22 genes related to bile adaption, including emrAB, acrRAB, galU, rfbC, tolC and mdtABC. This is the first study to reveal the whole genome sequence of the ZT1 strain of S. maltophilia isolated from human bile. We identified hundreds virulence factors and 22 bile adaptation-related genes in the genome of the S. maltophilia strain ZT1. Further comparative genomic analysis and functional verification would aid in understanding the pathogenesis and bile adaptation of S. maltophilia.


Increased apoptosis of peripheral blood lymphocytes in children with nephrotic syndrome.
Nephrotic syndrome is accompanied by and probably related to abnormal T-lymphocyte function. Decreased stimulation of survival factors and increased levels of "dead signals" may lead to the malfunction of many cells, including lymphocytes. In our study, we investigated the process of apoptosis within T cells in children with a first attack of nephrotic syndrome (NS). We found that the number of apoptotic T cells is greater in these patients than in both children in remission from NS and in controls. The percentage of annexin-V-fluorescein isothiocyanate (FITC)-positive CD3+ cells was 27.30+/- 12.13% in children with a first attack of NS, 19.22+/- 15.16% (P=0.006) in children in remission and 16.20+/- 6.13% (P=0.004) in controls. The percentage of annexin-V-FITC-positive CD3+CD4+ cells was 7.35+/-7.72% in children with a first attack of NS, 3.80+/-3.75% (P=0.0001) in children in remission and 3.82+/-2.01% (P=0.0002) in controls. We conclude that abnormal number and function of T lymphocytes found in NS patients may be related to an increased apoptotic rate of circulating lymphocytes.


Gracilis musculotendinous free flap for lower extremity reconstruction after surgical removal of malignant tumors: A report of five cases.
Lower extremity reconstruction is challenging because of the need to restore form and function. Despite the many options for soft-tissue coverage, little research has addressed combined tendon and soft-tissue reconstitution. We present a series of patients undergoing lower extremity tendon reconstruction and wound coverage with a single free gracilis flap and its tendon. We studied five patients (age range, 51-81 years) undergoing lower limb reconstruction for defects involving soft tissue and tendon between 1998 and 2016 in the senior author's practice. Wounds (all in the foot and ankle region) were caused by sarcoma (n = 4) and Merkel cell carcinoma (n = 1) and ranged from 6.5-10 × 8-12 cm. Donor tendons, 2-18 cm long, were used to reconstruct the tibialis anterior, extensor hallucis longus, extensor digitorum longus, and extensor retinaculum. Patient characteristics and outcomes were reviewed retrospectively. Reconstructions used a gracilis muscle free flap and its tendon. Flap sizes ranged 5-6.5 × 11-14 cm. Complications were one case of cellulitis and one case of reoperation for flap thinning and tenolysis. All patients had at least 7 months of follow-up (mean: 37 months; range: 7-104 months). At latest follow-up, all patients were ambulatory. On average, patients resumed assisted ambulation 27 days postoperatively and unassisted ambulation 62 days postoperatively. For complex wounds with soft-tissue and tendinous defects, the gracilis muscle free flap may be a reconstructive option. We recommend it be considered as a single-donor incision option for lower extremity reconstruction.


Neuroleptic withdrawal in treatment-resistant patients with schizophrenia: tardive dyskinesia is not associated with supersensitive psychosis.
The objective of this retrospective study was to determine whether tardive dyskinesia (TD) represents a risk factor for supersensitive psychosis (SS) by assessing the effect of medication withdrawal on ratings of psychopathology for 30 days following discontinuation of antipsychotic medication in patients with and without TD. The subjects were 101 treatment-resistant patients with schizophrenia who had been admitted to the inpatient service of Neuroscience Research Hospital (NRH), National Institute of Mental Health, between 1982 and 1994 to undergo studies involving discontinuation of antipsychotic medication. Patients were rated independently on a daily basis on the 22-item Psychiatric Symptom Assessment Scale (PSAS), an extended version of the Brief Psychiatric Rating Scale (BPRS). The overall frequency of TD was 35.6%. Tardive dyskinesia patients were older (p < 0.0006) and had suffered from schizophrenia for a longer time (p < 0.003) than No-TD patients. Repeated measure ANOVA revealed a "time" effect for all subgroups studied. The interaction TD x time, however, was not statistically significant for any of the clusters. Within-group analysis revealed significant differences against baseline for measures of positive symptoms, negative symptoms and abnormal involuntary movements in the No-TD group 3 and 4 weeks after antipsychotic withdrawal. In the TD group, however, the changes were observed only at 4 weeks following antipsychotic discontinuation in just two of the positive symptoms cluster. Between-group analyses revealed that, at baseline, the Mannerisms cluster (abnormal involuntary movements) was significantly higher in the TD group (p < 0.05). No significant differences were observed between any of the remaining clusters at baseline or at different times following drug withdrawal. In conclusion, the relationship between SS and TD could not be confirmed in a cohort of patients with treatment-resistant schizophrenia. In the present study, patients with no TD seemed to deteriorate faster than patients with TD in terms of psychopathology and abnormal involuntary movements. It is possible that both group of patients may undergo supersensitive receptor changes, and that these changes may be more pronounced but potentially reversible in the group without TD.


International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results.
To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow-up. We intended to recruit 2500 patients each in multi-bacillary (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field. A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine-related skin pigmentation was short-lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow-up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). U-MDT appears to be promising with respect to clinical status of skin lesions.


Hairy cell leukemia: in-vitro proliferation and pseudo-colony formation.
In an established double layer clonogenic assay, the PHA-leukocyte feeder colony assay, hairy cell leukemia (HCL) cells formed strong aggregates simulating colonies. After irradiation with 50 Gy, colony formation persisted. Even in a modified colony assay consisting of agar 0.5% overlayered by methylcellulose 0.9%, cell aggregation was still possible due to increasing fluidity of the methylcellulose during the culture period. Time-lapse video recordings confirmed prominent cell motility leading to pseudo-colony formation. Studies with bromodeoxyuridine incorporation showed a low proliferation index (up to 13%) of hairy cells. In conclusion, any assay that facilitates cell motility is unsuitable to study HCL colony growth.


Progressive lymphadenopathy and intractable pain in an immunocompetent African-American adult with cat-scratch disease.
Persistent, painful cervical lymphadenopathy associated with malaise that does not respond to oral antibiotics may be cat-scratch disease. This condition is challenging to treat and may require surgical intervention. We present a case report of an immunocompetent 47-year-old African-American woman who was diagnosed with cat-scratch disease and hospitalized after multiple outpatient evaluations for progressive, painful lymphadenopathy. This case report outlines the patient's treatment in the author's urban outpatient clinic followed by an inpatient hospital stay with surgical intervention. Although the reported incidence of cat-scratch disease is higher in whites, primary care physicians should include cat-scratch disease in their differential diagnosis for African-American patients with regional lymphadenopathy, which is a hallmark of the disease. In addition, primary care physicians should be familiar with the atypical presentations of cat-scratch disease and the broad differential diagnosis for regional lymphadenopathy, including sarcoidosis, which is more common in African Americans.


HIV prevalence and continuum of care among incarcerated people in Iran from 2010 to 2017.
Incarcerated people are at an increased risk of contracting HIV and transmitting it to the community post-release. In Iran, HIV epidemics inside prisons were first detected in the early 1990s. We assessed the HIV prevalence and its correlates, as well as the continuum of care among incarcerated people in Iran from 2010 to 2017. We used data collected in three national bio-behavioral surveillance surveys among incarcerated individuals in 2010 (n = 4,536), 2013 (n = 5,490), and 2017 (n = 5,785) through a multistage cluster sampling approach. HIV was tested by the ELISA method in 2010 and 2013 surveys and rapid tests in 2017. Data on demographic characteristics, risky behaviors, HIV testing, and treatment were collected via face-to-face interviews. HIV prevalence estimates along with 95% confidence intervals (CI) were reported. Using data from the 2017 round, multivariable logistic regression models were built to assess the correlates of HIV sero-positivity and conduct HIV cascade of care analysis. The HIV prevalence was 2.1% (95% CI: 1.2%, 3.6%) in 2010, 1.7% (95% CI: 1.3%, 2.1%) in 2013, and 0.8% (95% CI: 0.6%, 1.1%) in 2017 (trend P value < 0.001). Among people with a history of injection drug use, HIV prevalence was 8.1% (95% CI: 4.6%, 13.8%) in 2010, 6.3% (95% CI: 4.8%, 8.3%) in 2013, and 3.9% (95% CI: 2.7%, 5.7%) in 2017. In 2017, 64% (32 out of 50) of incarcerated people living with HIV were aware of their HIV status, of whom 45% (9 out of 20) were on antiretroviral therapy, and of whom 44% (4 out of 9) were virally suppressed (< 1000 copies/ml). While HIV prevalence has decreased among incarcerated people in Iran, their engagement in the HIV continuum of care is suboptimal. Further investments in programs to link incarcerated people to HIV care and retain them in treatment are warranted.


Premature ovarian insufficiency (POI) is the spontaneous or induced loss of ovarian function in women under the age of 40. POI increases the risk of reduced quality of life. Hormone replacement therapy may be beneficial in POI, but some women have contraindications. Recent studies indicate that exercise, yoga, meditation, acupuncture, and mindfulness may improve quality of life in women with POI. Phyto-oestrogens are not recommended in the treatment of POI since the physiological level of oestrogen cannot be achieved, and phyto-oestrogens should be avoided in women with present or previous breast cancer.


The Roux-Y loop in modern digestive tract surgery.
The technique of Y loop was utilized by César Roux beginning in January 1892 for antral or pyloric obstruction. He used the proximal jejunum to perform a Y gastroenterostomy. However, he abandoned the procedure in 1911, having noticed the frequency of late peptic ulcerations in the loop. Nevertheless, the Y-branching idea was later reconsidered and applications in hepatic, biliary, and pancreatic surgery were developed, as well as applications in gastrointestinal surgery. In this latter area, Roux-Y anastomoses are now performed primarily or secondarily. Primary uses include restoring the continuity of the alimentary tract after total gastrectomy (with or without a pouch), reconstruction after Whipple's procedure, repair of duodenal trauma, and intentional digestive bypass for morbid obesity. Secondary uses include remedial procedures after simple esophagojejunostomy, gastric fundus resection, and a Billroth II procedure to obviate postoperative complications due to bile reflux.


A new species of Tropidopedia from the Amazon rainforest, Brazil (Hymenoptera: Apidae), with a revised phylogenetic overview of the genus.
We describe a new species of the bee tribe Tapinotaspidini, Tropidopedia guaranae Mahlmann & Oliveira sp. n. from the Amazon rainforest, Amazonas, Brazil. We emend the phylogenetic tree of Aguiar & Melo (2007) to include the new species and comment upon some characters presented by those authors.


Fully covered Alimaxx esophageal metal stents in the endoscopic treatment of benign esophageal diseases.
Expandable esophageal stents are widely used for the palliation of dysphagia in patients with esophageal cancer and are also beginning to be used in patients with benign esophageal diseases such as refractory strictures and fistulas. There is concern regarding the increased risk of migration of the fully covered Alimaxx metal esophageal stent and experience with this stent in benign esophageal pathology has been reported in only a small series of patients. To evaluate the technical success in placement and removal, efficacy and complications of the Alimaxx esophageal stent for benign esophageal diseases. Our endoscopy database was retrospectively reviewed from 1/2003 to 2/2009 to identify patients with Alimaxx esophageal stent placement for benign diseases. Chart review was performed for age, gender, indication, site of the lesion, success of placement, outcome, and incidence of complications. Twenty-eight stents were successfully placed in 14 patients with benign esophageal diseases (mean: two stents/patient; range 1-7). Indications included esophageal fistula in seven (50%) and benign strictures in 7/14 (50%). Dysphagia improved in all patients while the fistula resolved in 6/7 (85.8%) patients. Complications related to stents included pain (2/28, 7%), stent related gastric ulcer (1/28, 4%), nausea and vomiting (3/21, 11%) and stent migration (11/28, 39%). All migrated stents were successfully endoscopically retrieved. The fully covered and removable Alimaxx stent is effective in the endoscopic management of benign esophageal strictures or fistulas, despite its relatively high rate of migration. Stent migration was successfully managed endoscopically without complications.