Effects of Personal Protective Equipment Use and Good Workplace Hygiene on Symptoms of Neurotoxicity in Solvent-Exposed Vehicle Spray Painters.
To assess the association between the use of personal protective equipment (PPE) and good workplace hygiene and symptoms of neurotoxicity in solvent-exposed vehicle spray painters. Exposure control measures including PPE-use and workplace hygiene practices and symptoms of neurotoxicity were assessed in 267 vehicle repair spray painters. Symptoms were assessed using an adapted version of the EUROQUEST Questionnaire. Frequent respirator and glove use was inversely and significantly associated with symptoms of neurotoxicity in a dose-dependent manner (P < 0.05 for trend) with the strongest protective effect found for consistent glove use (odds ratios [OR] 0.1-0.2, P < 0.01, for reporting ≥10 and ≥5 symptoms). A clear dose-response trend was also observed when combining frequency of respirator and glove use (P < 0.05 for reporting ≥5 and ≥10 symptoms), with an overall reduction in risk of 90% (OR, 0.1, P < 0.01) for those who consistently used both types of PPE. Protective effects were most pronounced for the symptom domains of psychosomatic (P < 0.05 for trend, for combined PPE use), mood (P < 0.05), and memory and concentration symptoms combined (P < 0.05), with reductions in risk of >80%. Poor hygiene workplace practices, such as solvent exposure to multiple body parts (OR 3.4, P = 0.11 for reporting ≥10 symptoms), were associated with an increased risk of symptoms. When using a general workplace hygiene score derived from a combination of PPE-use and (good) workplace practice factors an inverse and significant dose-response trend was observed for reporting ≥5 (P < 0.01) and ≥10 symptoms (P < 0.01). This study has shown that PPE-use and good workplace hygiene are associated with a strongly reduced risk of symptoms of neurotoxicity in solvent-exposed vehicle spray painters.


Expression profiling of peripheral-blood mononuclear cells from patients with chronic hepatitis C undergoing interferon therapy.
Interferon (IFN) is now the standard treatment for chronic hepatitis C (CH-C); however, treatment efficacy is unpredictable before IFN therapy is started. We investigated the gene-expression profiles of peripheral-blood mononuclear cells (PBMCs) from patients with CH-C showing different responses to IFN. Gene-expression profiles of PBMCs were analyzed in 21 patients with CH-C treated with IFN alone or in combination with ribavirin as well as in 6 healthy volunteers. Serial changes in the gene-expression profiles of PBMCs from individual patients were evaluated before treatment, 2 weeks after the start of IFN therapy, and 6 months after the completion of IFN therapy. Interestingly, the gene-expression profiles of PBMCs from patients with CH-C and healthy volunteers differed substantially; early T cell-activation antigen CD69 was significantly up-regulated in patients with CH-C, but immune-related molecules such as chemokine (C-C motif) receptor 2 and interleukin 7 receptor were significantly down-regulated. Selected combinations of expressed genes obtained before treatment and during IFN therapy by use of a fuzzy neural network combined with the SWEEP operator method predicted the outcome of IFN therapy with peak accuracies of 91.0% and 90.2%, respectively. These findings suggest that the gene-expression profiles of PBMCs from patients with CH-C may be useful biomarkers for IFN therapy.


[Ultrabraid SUTURE WITH FOOTPRINT RIVET FOR ANTERIOR CRUCIATE LIGAMENT TIBIAL EMINENCE AVULSION FRACTURE IN ADOLESCENTS UNDER ARTHROSCOPY].
To investigate the clinical effects of the Ultrabraid suture with FOOTPRINT rivet by arthroscopic technique for the treatment of anterior cruciate ligament (ACL) tibial eminence avulsion fracture. Between May 2011 and December 2013, 19 adolescent patients with ACL tibial eminence avulsion fracture were treated with arthroscopic reduction and fixation by Ultrabraid sutures with FOOTPRINT rivet. There were 13 males and 6 females with an average age of 15.8 years (range, 8-18 years). The left knees were involved in 10 cases and the right knees in 9 cases. The injury causes included traffic accident injury in 8 cases, sport injury in 6 cases, and sprain injury in 5 cases. Three patients had old fractures, and the others had fresh fractures. The results of Lachman test and anterior drawer test were both positive. The International Knee Documentation Committee (IKDC) subject score was 54.2 ± 4.0. Based on Meyers-McKeever classification, there were 3 cases of type II, 10 cases of type III, and 6 cases of type IV. The operation time was 50-60 minutes (mean, 55.2 minutes). X-ray film showed satisfactory fracture reduction at 1 day after operation. Primary healing of incision was obtained with no infection. Eighteen patients were followed up for 1-3 years (mean, 1.7 years). All fractures healed with smooth joint surface on the X-ray film at 3 months after operation. The results of Lachman test and anterior drawer test were both negative in 17 cases, and the results was negative for anterior drawer test and was weakly positive for Lachman test in 1 case. The IKDC subject score was significantly improved to 96.1 ± 2.1 at last follow-up (t = 34.600, P = 0.000). It could achieve early restoration of knee joint function to treat the ACL tibial eminence avulsion fracture by arthroscopic technique of the Ultrabraid suture with FOOTPRINT rivet because of satisfactory reduction, reliable fixation, small wound, and early rehabilitation.


Genomic and functional overlap between somatic and germline chromosomal rearrangements.
Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.


Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure.
Elevated serum uric acid concentrations have been observed in clinical conditions associated with hypoxia. Since chronic heart failure is a state of impaired oxidative metabolism, we sought to determine whether serum uric acid concentrations correlate with measures of functional capacity and disease severity. Fifty nine patients with a diagnosis of chronic heart failure due to coronary heart disease (n = 34) or idiopathic dilated cardiomyopathy (n = 25) and 20 healthy controls underwent assessment of functional capacity. Maximal oxygen uptake (MVO2) and regression slope relating to minute ventilation to carbon dioxide output (VE-VCO2) were measured during a maximal treadmill exercise test. Metabolic assessment consisted of measuring serum uric acid and fasting lipids, and insulin sensitivity, obtained by minimal modelling analysis of glucose and insulin responses during an intravenous glucose tolerance test. Clustering of indices of functional disease capacity and metabolic factors was explored using factor analysis and multivariate regression analysis. Compared to 20 healthy controls, patients with chronic heart failure had a 52% lower MVO2 (P < 0.001), 56.8% higher serum uric acid concentrations (P < 0.001) as well as a 60.5% lower insulin sensitivity (P < 0.001). Salient univariate correlations in the chronic heart failure group included serum uric acid concentrations with exercise time during the exercise test (r = -0.53), MVO2 (r = -0.50) (both P < 0.001), VE-VCO2 slope (r = 0.45), and NYHA functional class (r = 0.36) (both P < 0.01). In factor analysis of the chronic heart failure group, serum uric acid formed part of a principal cluster of metabolic variables which included MVO2 and VE-VCO2 slope. In multivariate regression analysis, serum uric acid concentrations emerged as a significant predictor of MVO2, exercise time (both P < 0.001,) VE-VCO2 slope and NYHA functional class (both P < 0.02), independent of diuretic dose, age, body mass index, serum creatinine, alcohol intake, plasma insulin levels, and insulin sensitivity index. There is an inverse relationship between serum uric acid concentrations and measures of functional capacity in patients with cardiac failure. The strong correlation between serum uric acid and MVO2 suggests that in chronic heart failure, serum uric acid concentrations reflect an impairment of oxidative metabolism.


Murine typhus. How does it affect us in the 21st century? The epidemiology of inpatients in Spain (1997-2015).
The aim of this study was to analyze the epidemiological impact of murine typhus in patients who required hospitalization in the National Health System (SNS) in Spain between 1997 and 2015. Murine typhus (MT) is a zoonosis caused by Rickettsia typhi. MT is transmitted from rats, cats, dogs, and opossums to humans by their fleas. The clinical picture is characterized by headache, fever, rash, and liver function alteration. The prevalence of MT is considered underestimated since most cases are mild and self-limited. However, up to 10% of patients develop serious complications such as pneumonia or acute kidney injury and may even need admission to intensive care units. This was a retrospective longitudinal descriptive study of inpatients diagnosed with Rickettsia typhi infection (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], 081.0) in Spanish public hospitals between January 1, 1997, and December 31, 2015. Data were obtained from the Minimum Basic Data Set (MBDS, CMBD in Spanish), which includes information about inpatients admitted to the National Health System (NHS) hospitals provided by the Health Information Institute of the Ministry of Health and Equality. Ninety-nine inpatients were included. The incidence rate of MT was 0.12 (95% CI, 0.09-0.14) cases per one million person-years. Cases were irregularly distributed throughout the period of study, with a slight upward trend between 2013 and 2015. The Canary Islands had the highest incidence rate: 2.17 (95% CI, 1.69-2.64) cases per one million person-years (80 cases). Most patients were men (63.6%). The mean age (±SD) was 46.4 years (±19). Five patients were under 15 years old. Approximately 85.9% of cases required urgent hospital admissions. The average hospital stay was 11 days (±9.9). Only 1 patient died. Although considered uncommon, the incidence of MT seems to be increasing slowly. Most cases occurred in middle-aged men between late summer and early autumn in Spain. The Canary Islands and Andalusia registered the highest number of cases. The MBDS is an appropriate approach to study MT hospital management.


Divalproex sodium extended-release for the prophylaxis of migraine headache in adolescents: results of a stand-alone, long-term open-label safety study.
The objective of this long-term open-label study in adolescents was to assess the safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches. Two formulations of divalproex sodium have demonstrated efficacy in the prevention of migraine headaches in adults. However, no medications are currently approved for this indication in adolescents, and long-term safety data on agents for migraine prevention are lacking for this younger population. Therefore, the current study was conducted to assess the long-term safety and tolerability of divalproex extended-release in adolescents with migraine headaches. This was a 12-month, phase 3, open-label, multicenter study of adolescents aged 12 to 17 years with migraine headaches diagnosed by International Headache Society criteria. Divalproex sodium extended-release was initiated at 500 mg/day for 15 days then increased to 1000 mg daily, with subsequent adjustments permitted within a dosing range of 250-1000 mg daily. Study visits were conducted at days 1 and 15 and months 1, 2, 3, 6, 9, and 12. Safety was evaluated by adverse event collection, laboratory assessments, physical and neurological examinations, vital signs, electrocardiograms, the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, the Wechsler Abbreviated Scale of Intelligence, and the Behavioral Assessment Scale for Children. Efficacy was evaluated by following the number of migraine headache days reported in subjects' headache diaries over sequential 4-week intervals for the duration of the trial. A total of 241 subjects were enrolled and treated. The most frequently reported adverse events were nausea (19%), vomiting (18%), weight gain (12%), nasopharyngitis (11%), migraine (10%), and upper respiratory tract infection (10%). Ten (4%) subjects experienced serious adverse events, and 40 (17%) subjects discontinued because of an adverse event. Increases in ammonia levels were observed. No other clinically significant changes were observed in laboratory values, vital signs, rating scales, or electrocardiograms. Median 4-week migraine headache days decreased 75% between the first and the fourth months of the study (from 4.0 to 1.0) and remained at or below this level for the remainder of the study. In this long-term open-label study of adolescents with migraine, the safety and tolerability profile of divalproex sodium extended-release was consistent with findings from previous trials in adults, as well as 2 studies recently completed in adolescents. In general, divalproex sodium extended-release was well-tolerated in adolescents with migraine.


Mobile Application for Adaptive Threshold Hunting in Transcranial Magnetic Stimulation.
Application of transcranial magnetic stimulation (TMS) is expanding with many studies applying adaptive threshold hunting to determine a motor threshold (MT). In addition to being a measure of corticospinal excitability, the MT is used as a baseline stimulation intensity (SI) to which following investigative or modulatory SIs are referenced to. Currently available tools for determining MTs include system-integrated tools and third-party stand-alone software. System-integrated MT-tools are still rarely available and the stand-alone software usually demand a separate computer, and hence possess additional space-requirements. I introduce and validate a free Android-based mobile application ("ATH-tool") for adaptive threshold hunting of the MT. The objective is to allow for a simple and validated recording of MTs with sharing capabilities for logs. For comparison, I applied Motor Threshold Assessment Tool 2.0, to compare the MT-values determined with the new application, as it applies closely the same routine. Computational validation with known true threshold values confirmed that the new application captured the true MT at high precision (error ≤ 0.9%). Previously published data on motor evoked potentials (MEPs) were used to simulate realistic response occurrence by considering experimental data from 15 healthy subjects at different stimulation intensities. The MTs of the different methods agreed well (ICC ≥ 0.971, ). There was no significant difference between the MTs determined with the different methods ( p ≥ 0.151 ). The novel mobile application should make it easier for researchers and clinicians to determine MTs and log the results.


Sterol carrier protein2: further evidence for its role in adrenal steroidogenesis.
Homogeneous rat liver sterol carrier protein (SCP2) has been implicated in adrenal steroidogenesis by studies utilizing as a model system various sub-cellular fractions of rat adrenals. Levels of SCP2 were measured in rat adrenal subcellular fractions and various rat tissues using a highly sensitive radioimmunoassay. The levels of SCP2 in various tissues correlate well with the capacity of each tissue to either synthesize or metabolize cholesterol. The high level of SCP2 in adrenal mitochondria (46% of total tissue SCP2) is consistent with its proposed role of enhancing transfer of cholesterol from the outer to the inner mitochondrial membrane. Neither ACTH nor cycloheximide treatment of rats had a significant effect on SCP2 levels or distribution in the adrenal subcellular fractions. Western blot analysis of adrenal subcellular fractions indicates the presence of a protein of identical molecular weight and at least similar antigenicity as homogeneous rat liver SCP2. In the present studies, intact dispersed rat adrenal fasciculata cells fused with liposomal encapsulated anti-SCP2 IgG showed a 40-65% reduction in their ability to produce corticosterone when stimulated with ACTH. The steroidogenic competence of these anti-SCP2 IgG treated cells can be restored by treatment of the cells with liposomal encapsulated SCP2 prior to ACTH stimulation. These findings provide direct evidence for the involvement of SCP2 in ACTH stimulated steroidogenesis in rat adrenocortical cells, and suggests that SCP2 may not be the putative high turnover "labile protein" involved in acute steroidogenesis.


Carbonized rice husk coated solar absorber for clean water generation from seawater with a solar still.
This study demonstrated the generation of clean water from seawater collected at the beach coast in Universiti Malaysia Sabah, Malaysia, with carbonized rice husk coated melamine sponge as solar absorber by a solar still. Melamine sponge was utilized as a seawater transportation medium since its porous structure is excellent in channelling the seawater. Whereas carbonized rice husk was used as the photothermal conversion material for its efficient heat absorption due to its black colour and porous structure. Implementing air gap between the seawater body and solar absorber, and restricted water pathway assisted in localizing heat on the top surface of the solar absorber. Clean water was generated under direct solar radiation during the day at an open space with average solar intensity around 1.1∼1.2 kW/m2 (slightly higher than 1 sun) for about 4 h. Efficiency of the solar absorber was calculated, while the quality of the generated clean water was observed in terms of salinity and pH value. Insulated solar still with carbon-coated sponge showed the highest efficiency at about 54.74%. Salinity of the collected clean water significantly reduced to consumable level which was approximately 55 ppm, and the pH value at about 6.73 where it was within the safe limit of the drinkable water pH.


Dysregulation of Microtubule Stability Impairs Morphofunctional Connectivity in Primary Neuronal Networks.
Functionally related neurons assemble into connected networks that process and transmit electrochemical information. To do this in a coordinated manner, the number and strength of synaptic connections is tightly regulated. Synapse function relies on the microtubule (MT) cytoskeleton, the dynamics of which are in turn controlled by a plethora of MT-associated proteins, including the MT-stabilizing protein Tau. Although mutations in the Tau-encoding MAPT gene underlie a set of neurodegenerative disorders, termed tauopathies, the exact contribution of MT dynamics and the perturbation thereof to neuronal network connectivity has not yet been scrutinized. Therefore, we investigated the impact of targeted perturbations of MT stability on morphological (e.g., neurite- and synapse density) and functional (e.g., synchronous calcium bursting) correlates of connectivity in networks of primary hippocampal neurons. We found that treatment with MT-stabilizing or -destabilizing compounds impaired morphofunctional connectivity in a reversible manner. We also discovered that overexpression of MAPT induced significant connectivity defects, which were accompanied by alterations in MT dynamics and increased resistance to pharmacological MT depolymerization. Overexpression of a MAPT variant harboring the P301L point mutation in the MT-binding domain did far less, directly linking neuronal connectivity with Tau's MT binding affinity. Our results show that MT stability is a vulnerable node in tauopathies and that its precise pharmacological tuning may positively affect neuronal network connectivity. However, a critical balance in MT turnover causes it to be a difficult therapeutic target with a narrow operating window.


Testing the safety of non-disconnect disposable Y sets for peritoneal dialysis.
In order to test the efficacy of the Del Clamp as a contamination barrier, the following protocol was carried out. Sixty bags of dialysate (1.5 L, 1.5% Dextrose) were connected to matching disposable Y sets and 100 mL of dialysate allowed to flow into each drain bag, after which the clamps were closed. The bags were arranged in groups of 10 and each group was inoculated with 1 mL of a standard suspension of S. aureus, S. epidermidis, E. coli, E. faecalis, P. aeruginosa and C. albicans, respectively. 3 bags were inoculated and left with the clamp open as controls. After 6 hr, incubation at 37 degrees C, 20 mL duplicate samples from each drain bag were centrifugated and processed for anaerobic and aerobic culture. None of the specimens taken from the sets grew bacteria or fungi. All the drain bags of the control sets grew the inoculated organism. We conclude that the Del Clamp makes CAPD safer by working as an effective contamination barrier and eliminating a potential for combination during the dialysis exchange.


Neural Regulatory Pathways of Feeding and Fat in Caenorhabditis elegans.
The compact nervous system of Caenorhabditis elegans and its genetic tractability are features that make this organism highly suitable for investigating energy balance in an animal system. Here, we focus on molecular components and organizational principles emerging from the investigation of pathways that largely originate in the nervous system and regulate feeding behavior but also peripheral fat regulation through neuroendocrine signaling. We provide an overview of studies aimed at understanding how C. elegans integrate internal and external cues in feeding behavior. We highlight some of the similarities and differences in energy balance between C. elegans and mammals. We also provide our perspective on unresolved issues, both conceptual and technical, that we believe have hampered critical evaluation of findings relevant to fat regulation in C. elegans.


Matrix metalloproteinase-3 is increased and participates in neuronal apoptotic signaling downstream of caspase-12 during endoplasmic reticulum stress.
Although endoplasmic reticulum (ER) stress-induced apoptosis has been associated with pathogenesis of neurodegenerative diseases, the cellular components involved have not been well delineated. The present study shows that matrix metalloproteinase (MMP)-3 plays a role in the ER stress-induced apoptosis. ER stress induced by brefeldin A (BFA) or tunicamycin (TM) increases gene expression of MMP-3, selectively among various MMP subtypes, and the active form of MMP-3 (actMMP-3) in the brain-derived CATH.a cells. Pharmacological inhibition of enzyme activity, small interference RNA-mediated gene knockdown, and gene knock-out of MMP-3 all provide protection against ER stress. MMP-3 acts downstream of caspase-12, because both pharmacological inhibition and gene knockdown of caspase-12 attenuate the actMMP-3 increase, but inhibition and knock-out of MMP-3 do not alter caspase-12. Furthermore, independently of the increase in the protein level, the catalytic activity of MMP-3 enzyme can be increased via lowering of its endogenous inhibitor protein TIMP-1. Caspase-12 causes liberation of MMP-3 enzyme activity by degrading TIMP-1 that is already bound to actMMP-3. TIMP-1 is decreased in response to ER stress, and TIMP-1 overexpression leads to cell protection and a decrease in MMP-3 activity. Taken together, actMMP-3 protein level and catalytic activity are increased following caspase-12 activation during ER stress, and this in turn plays a role in the downstream apoptotic signaling in neuronal cells. MMP-3 and TIMP-1 may therefore serve as cellular targets for therapy against neurodegenerative diseases.


Use of standards in the review of medical devices.
In keeping with its mandate to provide the least burdensome means of product regulation, the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health uses many different standards to facilitate the review of premarket submissions of medical devices. The benefits of using standards in this manner include providing a set of common requirements and test protocols to the device manufacturer, thus reducing the manufacturer's need to "reinvent the wheel" for each new bench test to ensure safety and effectiveness of the device. With the current trend toward international harmonization of standards, tests performed in accordance with an international standard may be acceptable to several countries. However, there are instances in which the FDA does not agree with certain provisions in a standard. This article aims to clarify the approaches taken by the FDA to balance or resolve issues that arise when there is disagreement regarding the acceptability of a particular standard. One approach begins with the recognition of only some provisions of a standard, or more commonly, excluding those parts of a standard that are unacceptable to the FDA for regulatory or scientific validity reasons. Other approaches include working with the standards development organizations to revise the standard to include language more agreeable to all parties involved. Specific examples will be presented on medical devices, such as electrocardiogram cables and connectors, and noninvasive blood pressure monitors.


Goserelin acetate 10.8 mg plus iron versus iron monotherapy prior to surgery in premenopausal women with iron-deficiency anemia due to uterine leiomyomas: results from a Phase III, randomized, multicenter, double-blind, controlled trial.
Women with symptomatic uterine leiomyomas (fibroids) may have iron-deficiency anemia (IDA); therefore, surgery places them at risk of blood-borne morbidity from perioperative transfusions. Such women might benefit from a preoperative treatment that restores hematologic normality and alleviates fibroid symptoms. The purpose of this study was to examine the effects of a single preoperative depot injection of goserelin acetate plus iron treatment compared with iron monotherapy, in premenopausal women with IDA due to uterine leiomyomas. This Phase III, randomized, multicenter, double-blind, controlled trial (12 weeks of treatment plus a 24-week follow-up period) was conducted from October 1997 to August 1999. Patients received an injection of goserelin acetate 10.8 mg (3-month formulation) or a sham, with both groups receiving PO iron (ferrous sulfate) 325-mg tablets TID during the 12-week treatment period. Surgery (hysterectomy or myomectomy) was planned for week 12. Hemoglobin (Hb) level, symptoms of uterine leiomyomas, requirement for blood transfusion throughout, ability to donate blood for autologous transfusion, and leiomyoma and uterine volume were assessed for efficacy. The tolerability assessment included bone mineral density measurements and subjective symptomatology (ie, menstrual bleeding [uterine hemorrhage], fatigue, pelvic pain, and pelvic pressure). A total of 110 women received treatment (n = 54, goserelin acetate 10.8 mg; n = 56, sham). The majority of patients (69.1%) were black and the mean age at study entry was 39.9 years, with a mean weight of 80.1 kg. At approximately 12 weeks, Hb levels were significantly higher in the goserelin group compared with the sham group (difference of least squares mean, 1.17 g/dL; 95% CI, 0.68-1.66; P < 0.001), and significantly more patients in the goserelin group had an increase in Hb concentration of >or=2 g/dL (odds ratio 6.36; 95% CI, 2.00-20.18; P < 0.001). A nonsignificant decrease in both uterine and leiomyoma volume was experienced by patients who administered goserelin compared with increases in the sham group. Uterine hemorrhage was also experienced numerically less often by goserelin-treated patients compared with those given the sham injection (9.3% vs 28.6%, respectively). One or more adverse events (AEs) were reported by 89% of patients in each treatment group. Goserelin acetate 10.8 mg was generally well tolerated by patients, with no serious drug-related AEs reported during this 36-week trial. A single, preoperative injection of goserelin acetate 10.8 mg in addition to PO iron 325 mg TID was associated with improved Hb levels in these premenopausal women with IDA due to uterine leiomyomas.


Quantum Otto engine of a two-level atom with single-mode fields.
We establish a quantum Otto engine (QOE) of a two-level atom, which is confined in a one-dimensional (1D) harmonic trap and is coupled to single-mode radiation fields. Besides two adiabatic processes, the QOE cycle consists of two isochoric processes, along one of which the two-level atom as the working substance interacts with a single-mode radiation field. Based on the semigroup approach, we derive the time for completing any adiabatic process and then present a performance analysis of the heat engine model. Furthermore, we generalize the results to the performance optimization for a QOE of a single two-level atom trapped in a 1D power-law potential. Our result shows that the efficiency at maximum power output is dependent on the trap exponent θ but is independent of the energy spectrum index σ.


Effects of whole deletion of CYP2A6 on nicotine metabolism in humans.
We investigated the effects of CYP2A6 genotypes on nicotine metabolism, focused from nicotine to cotinine and its additional 3'-hydroxylating resulted in trans-3'-hydroxycotinine formation. In the subjects genotyped by PCR-RFLP method, one cigarette smoking experiment was performed and urine samples were collected for 24 h. In all subjects who smoked, we detected nicotine, cotinine and trans-3'-hydroxycotinine in urine by GC-MS analysis. In whole deletion of CYP2A6, urinary excretion amounts of cotinine and trans-3'-hydroxycotinine were significantly smaller than those in the wild-type of CYP2A6*1. A lack of CYP2A6 reduces the formation of cotinine and trans-3'-hydroxycotinine, but not entirely reduces the trans-3'-hydroxycotinine formation. Unknown cotinine 3'-hydroxylating activity except CYP2A6 are suspected in humans.


Early renal arterial rupture and arterial pseudoaneurysm in graft kidneys from the same deceased donor.
Vascular complications are serious problems after kidney transplantation. An aneurysm or rupture in a graft artery is a rare but potentially devastating complication, which may lead to renal function impairment, graft loss, or even death. In this paper, we present two rare vascular complications in the early postoperative course after renal transplantation from the same deceased donor. In the first case, a 49-year-old woman who had spontaneous graft arterial rupture 13 days after kidney transplantation presented with sudden distension in the right lower abdomen. In the second case, a 56-year-old woman recipient with a graft renal arterial pseudoaneurysm presented with decreased urine output and deteriorating renal function 32 days after transplantation. Immediate surgical repair was performed, and fibrin sealant was applied to strengthen the fragile renal arterial wall. Although the function of both graft kidneys recovered well after surgery, the first graft kidney was removed 2 months later because of repeated fungal and bacterial infections. Aggressive surgical reconstruction may preserve graft kidneys in patients with vascular complications after kidney transplantation, but recovery of the graft condition remains a demanding challenge in renal transplantation.


[How to change physicians' practice--health services research with the knowledge-performance gap on focus].
How can the knowledge-performance gap be bridged? The discrepancy between our scientific knowledge on the one hand and its inadequate application in everyday practice on the other remains a major challenge for implementation research. Looking back on ten years of Health Services Research and acknowledging the achievements of educational research we have gained access to a variety of research findings and tools describing how physicians'--and other health professionals'--behavior and performance in medical care may be influenced. The time has come for testing and evaluating them.


Child maltreatment and children's developmental trajectories in early to middle childhood.
Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Wellbeing Study, a birth cohort of 4,898 children followed from birth through age 9. Hierarchical linear modeling and structural equation modeling are employed to estimate associations of maltreatment with cognitive and social-emotional well-being. Results suggest that effects of early childhood maltreatment emerge immediately, though developmental outcomes are also affected by newly occurring maltreatment over time. Additionally, findings indicate that children's early developmental scores predict their subsequent probability of experiencing maltreatment, though to a lesser extent than early maltreatment predicts subsequent developmental outcomes.


[Early and Late Outcomes of Valve Surgery in Active Infective Endocarditis Patients with Cerebral Complications].
We carried out a retrospective evaluation of the early and late outcomes of valve surgery for acute endocarditis patients with cerebrovascular disease. Between January 2002 and August 2014, a total of 17 patients (early group, n=10;delayed group, n=7) underwent valve surgery with or without an additional procedure. Craniotomy was performed in 1 patient in the early group and 2 patients in the delayed group before valve surgery. There was 1 in-hospital death due to acute respiratory distress syndrome in the early group and 1 death due to intestinal bleeding in the delayed group. Postoperative deterioration was observed in 1 in the delayed group. Overall survival in the early group was 90% and was not significantly different from survival in the delayed group (86%). In conclusion, our study demonstrated good early and mid-term outcomes for valve surgery in active endocarditis patients with cerebrovascular disease. There was no postoperative deterioration in the early group. Thus, an early operation for these patients may be acceptable.


Managing an emergency department by analysing HIS medical data: a focus on elderly patient clinical pathways.
The objective of this paper is to present complementary views of the activity of the emergency department for a specific group of patients. Once validated, these views will be used as decision support tools for better managing the department and providing better care delivery for this population. The views are produced from the data stored in Healthcare Information Systems that correspond potentially to a vast source of information for supporting decisions on management or public health issues. The study focuses on two groups of patients: the elderly population (over 75-years-old) and the under 75-year-old patients, at the Rennes hospital. The validation of the views is performed by comparing results for the two distinct groups. Relevant data were extracted from the Emergency Department database. Several analysis (like cusum chart) and representation tools (Graphviz) were used to study the patients' pathways, the dynamics of arrivals and the patients' characteristics. The representations provided a synthetic, global and comprehensive view of the department activities, to the satisfaction of the clinicians. The study showed that ICD-10 coding, assigned at the patient's departure from the emergency department hence from all available known clinical data, is not appropriate for the elderly population as these patients are mainly diagnosed by "symptoms" and several solutions are proposed. Finally, it is stressed out that a proper delivery of care to elderly patients should require some level of scheduling in the emergency department that is by essence characterized by its non scheduled activity.


[Leukocytapheresis for ulcerative colitis].
Major inclusion criteria for leukocytapheresis (LCAP) therapy were mainly insufficient response to conventional drugs therapy. LCAP was administered once a week for 5 weeks of intensive therapy and once approximately a month for maintenance therapy, for 38 patients with UC. LCAP could remove approximately 1 x 10(10) white blood cells in each session. In the evaluation, we classified the response to the LCAP as: 1) excellent, 2) moderately improved, 3) no change, and 4) deterioration. Clinical improvement was recognized in 29 of 38 patients (76%) including 8 with dramatic response during the intensive therapy, and continued throughout the maintenance therapy in 26 patients (68.4%). Even though their symptoms were mild, the patients with more than 5 years UC history seemed to be not effective. The patients with moderately improvement and with excellent response have kept remission for about 20 months and about 2.5 years on an average, respectively. Clinical and blood examinations showed no side effects in any cases. It suggests that LCAP is able to be a UC treatment between drug therapies and an operation.


Morphea after Silicone Implants.
Dear Editor, Silicone is a hydrophobic polymer containing silicon. Silicon is an essential compound of soft tissue proteoglycans. Reports about morphea and other autoimmune connective tissue disorders in association with silicone implants have stimulated the discussion of a possible link between the two, such as immunological cross-reactivity of silicone and connective tissue components (1). A number of case reports suggested a possible link to adjuvant autoimmune syndrome (2), morphea of the breast (3-5), and systemic scleroderma (6-8), among others. One study measured tissue silicon levels in women with silicone breast implants with and without symptoms or signs and compared these data with women who had either a saline breast implant or no augmentation at all. The authors detected higher levels of silicon in capsular tissue of patients with silicone implants, independent of the presence of any symptoms or signs (9,10). The conclusion was that there is no evidence of an association between silicone implants and autoimmune connective tissue disorders. Three other clinical trials investigating the role of silicone implants and induction of autoimmune connective tissue disorders also failed to find an association between the two (11-13). We report the case of a 32-year-old female patient who developed morphea of the breasts after silicone implants for augmentation after risk-reducing mastectomy for Cowden syndrome. She presented with pronounced capsule fibrosis of the implants. With a delay of several years, an ill-defined slightly hyperpigmented area developed on the breasts and ventral chest (Figure 1). The lesion was analyzed by dermoscopy (Figure 2), which found mild erythema, reduced vessels, and white areas (ill-defined dull white globules, fibrotic beams). A skin biopsy was taken. Histopathological analysis showed a normal epidermal layer, minor papillary edema, and some vascular ectasias in the papillary dermis and upper corium (Figure 3). There was mild perivascular inflammatory infiltrate of the deep dermal vascular plexus, composed of lymphocytes and monocytes with some plasma cells (Figure 4). Elastic fibers seemed unaffected (Figure 5). The diagnosis of an early morphea of the edematous-inflammatory stage was established. Treatment with topical corticosteroids and UVB-311 nm irradiation was recommended. Morphea of the breasts is an uncommon disorder. It may occur after radiotherapy of breast cancer, after silicone augmentation, or without any known cause (14-16). A meta-analysis found an increased risk for morphea/scleroderma, with a relative risk between 1.30 to 2.13 and an odds ratio for case control studies of 1.68 (17). The US FDA Breast Implant Approval Study evaluated almost 100,000 female patients with breast implants. An increased risk of Sjögren's syndrome, scleroderma, and rheumatoid arthritis was reported (18). We could not find any reference of an association between capsular fibrosis and morphea of the breast, although both represent fibrotic disorders. In conclusion, it seems possible that there is a link between morphea of the breast and chest as described herein and silicone breast implants, which is supported by epidemiological studies. However, a direct causal relationship is hard to demonstrate with a single case.


Pharmacological therapy for myocardial infarction in the elderly: An 8-year analysis.
To assess the changes in the medicamentous treatment of elderly patients hospitalized with acute myocardial infarction occurring over an 8-year period. We retrospectively analyzed 379 patients above the age of 65 years with acute myocardial infarction who were admitted to the coronary unit of a university-affiliated hospital from 1990 to 1997. The patients were divided into 2 groups, according to the period of time of hospital admission as follows: group 1 - from 1990 to 1993; and group 2 - from 1994 to 1997. The use of beta-blockers (40.8% X 75.2%, p<0.0001) and angiotensin-converting enzyme inhibitors (42% X 59.5%, p=0.001) was significantly greater in group 2, while the use of calcium antagonists (42% X 18.5%, p<0.0001) and general antiarrhythmic drugs (19.1% X 10.8%, p=0.03) was significantly lower. No significant difference was observed in regard to the use of acetylsalicylic acid, thrombolytic agents, nitrate, and digitalis in the period studied. The length of hospitalization was shorter in group 2 (13.4+/-8.9 days X 10.5+/-7.5 days, p<0.001). The in-hospital mortality was 35.7% in group 1 and 26.6% in group 2 (p=0.07). Significant changes were observed in the treatment of elderly patients with acute myocardial infarction, with a greater use of beta-blockers and angiotensin-converting enzyme inhibitors and a lower use of calcium antagonists and antiarrhythmic drugs in group 2. The length of hospitalization and the mortality rate were also lower in group 2, even though the reduction in mortality was not statistically significant.


Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate.
Drug resistance against dihydrofolate reductase (DHFR) inhibitors-such as pyrimethamine (PM)-has now spread to almost all regions where malaria is endemic, rendering antifolate-based malaria treatments highly ineffective. We have previously shown that the di-amino quinazoline QN254 [5-chloro-N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine] is active against the highly PM-resistant Plasmodium falciparum V1S strain, suggesting that QN254 could be used to treat malaria in regions with a high prevalence of antifolate resistance. Here, we further demonstrate that QN254 is highly active against Plasmodium falciparum clinical isolates, displaying various levels of antifolate drug resistance, and we provide biochemical and structural evidence that QN254 binds and inhibits the function of both the wild-type and the quadruple-mutant (V1S) forms of the DHFR enzyme. In addition, we have assessed QN254 oral bioavailability, efficacy, and safety in vivo. The compound displays favorable pharmacokinetic properties after oral administration in rodents. The drug was remarkably efficacious against Plasmodium berghei and could fully cure infected mice with three daily oral doses of 30 mg/kg. In the course of these efficacy studies, we have uncovered some dose limiting toxicity at higher doses that was confirmed in rats. Thus, despite its relative in vitro selectivity toward the Plasmodium DHFR enzyme, QN254 does not show the adequate therapeutic index to justify its further development as a single agent.


Lectin staining and flow cytometry reveals female-induced sperm acrosome reaction and surface carbohydrate reorganization.
All cells are covered by glycans, an individually unique layer of oligo- and polysaccharides that are critical moderators of self-recognition and other cellular-level interactions (e.g. fertilization). The functional similarity between these processes suggests that gamete surface glycans may also have an important, but currently overlooked, role in sexual selection. Here we develop a user-friendly methodological approach designed to facilitate future tests of this possibility. Our proposed method is based on flow cytometric quantification of female-induced sperm acrosome reaction and sperm surface glycan modifications in the Mediterranean mussel Mytilus galloprovincialis. In this species, as with many other taxa, eggs release water-soluble factors that attract conspecific sperm (chemoattraction) and promote potentially measurable changes in sperm behavior and physiology. We demonstrate that flow cytometry is able to identify sperm from other seawater particles as well as accurately measure both acrosome reaction and structural modifications in sperm glycans. This methodological approach can increase our understanding of chemically-moderated gamete-level interactions and individual-specific gamete recognition in Mytilus sp. and other taxa with similar, easily identifiable acrosome structure. Our approach is also likely to be applicable to several other species, since carbohydrate-mediated cellular-level interactions between gametes are universal among externally and internally fertilizing species.


Differential activation and tyrosine hydroxylase distribution in the hippocampal, pallial and midbrain brain regions in response to cognitive performance in Indian house crows exposed to abrupt light environment.
Disruption of the cyclic feature of the day-night environment can cause negative effects on daily activity and advanced brain functions such as learning, memory and decision-making behaviour. These functions in songbirds, including corvids, involve the hippocampus, pallium and midbrain, as revealed by ZENK (a neuronal activation marker) and tyrosine hydroxylase (TH) expressions. TH is rate-limiting marker enzyme of the biosynthesis of dopamine, widely implicated in learning and memory. Here, we measured ZENK and TH immunoreactivity in the hippocampal, pallial and midbrain regions in response to cognitive performance (learning-memory retrieval) tests in Indian house crows (Corvus splendens) exposed to constant light environment (LL) with controls on 12h light:12h darkness. Along with the decay of circadian rhythm in activity behaviour, LL caused a significant decline in the cognitive performance. There was also a decrease under LL in the activity of neurons in the hippocampus, medial and central caudal nidopallium, and hyperpallium apicale, which are widely distributed with TH-immunoreactive fibres. Further, under LL, TH- immunoreactive neurons were reduced in number in midbrain dopamine synthesis sites, the venteral tegmental area (VTA) and substantia nigra (SN), with a negative correlation of co-localized ZENK/TH- immunoreactive cells on errors during the association tasks. These results show decreased activity of learning and memory neural systems, and underscore the role of dopamine in reduced cognitive performance of diurnal corvids with disrupted circadian rhythms under an abrupt light environment.


Angiogenesis in the primate ovary.
The ovary is distinctive in undergoing cyclic changes in angiogenesis that play a critical role in the normal functioning of the female reproductive system. The current paper describes the use of the marmoset monkey as an in vivo model in which the cellular and molecular regulation of angiogenesis in the ovary can be investigated and the effects of manipulation of angiogenic factors elucidated. The studies are based on quantifying changes in blood vessel area and endothelial cell proliferation, monitoring changes in expression patterns of putative angiogenic regulatory factors and targeting these factors by antagonists in vivo. Quantification of endothelial cell proliferation shows that angiogenesis commences in the pre-antral follicle, increases with follicular development and becomes intense in the early corpus luteum. Vascular endothelial growth factor (VEGF), a principal angiogenic factor, is synthesized by the developing follicle and corpus luteum. Administration of specific antagonists in vivo for selected periods of the ovulatory cycle shows that inhibition of VEGF results in a marked decrease in endothelial cell proliferation in the follicle and is accompanied by a decline in granulosa cell proliferation. Inhibition during the early or mid-luteal phase results in a marked suppression in luteal angiogenesis, failure of development of the microvascular tree and suppression of luteal function. Manipulation of angiogenesis should be a novel approach to either promoting or inhibiting the normal processes of folliculogenesis, ovulation and corpus luteum function.


Primary adenoid cystic carcinoma of the esophagus. Report of a case and its histochemical characterization.
A case of primary adenoid cystic carcinoma of the esophagus was reported. A 54-year-old male patient had a tumor in the middle third of the esophagus. Barium swallow and endoscopic examination showed a protruding tumor with a shallow ulceration in its vertex. Histological examination of the surgically removed material revealed that it was largely confined to the submucosal layer, with no metastasis to lymph nodes. The tumor cells presented three distinct patterns: globular nest with irregular cystic spaces, trabecular nest, and true tubule. Electron microscopic study revealed no microvilli or triad along cystic spaces in the globular nests. Histochemical study disclosed that cystic spaces and interstitium were rich in glycosaminoglycans. The luminal surface of the true tubules of the tumor, on the other hand, was characteristically lined by sialomucins. The trabecular type-nests differed from the globular nests in showing GSA-II reactivity and containing abundant retinol-binding protein. These results indicate that the three patterns represented different differentiations of the tumor cells. Twenty-three cases of esophageal adenoid cystic carcinoma were found in the literature from 1950 to 1983 and discussed collectively.


Frequency modulation versus amplitude modulation discrimination: evidence for a second frequency modulation encoding mechanism.
The encoding mechanisms for amplitude modulation (AM) and frequency modulation (FM) were investigated using AM-FM discrimination tasks. In the first experiment, AM and FM were set at equally detectable levels within a trial, and discrimination thresholds were obtained adaptively in a 3IFC task. Here, AM-FM discrimination thresholds were considerably larger than both AM and FM detection thresholds. This is consistent with an encoding system whereby AM and FM are partially encoded by the same mechanism. In the second experiment, performance on AM-FM discrimination is measured with a fixed-level procedure. Psychometric functions obtained for a constant modulation depth of AM were nonmonotonic with FMs modulation index beta and each displayed a single minimum. The nonmonotonic nature of the functions is consistent with a model in which FM is encoded primarily with the same mechanism that encodes AM but also with a second mechanism, probably related to changes in instantaneous frequency, that is independent of the mechanism that extracts AM. The fact that minima in the discrimination psychometric functions increase from d' = 0 as beta increases indicates that the information encoded by the second mechanism becomes more detectable with increasing beta.


Bioremediation of toluene and naphthalene: development and validation of a GC-FID method for their monitoring.
Bioremediation of toluene and naphthalene in liquid cultures of bacteria grown in the presence of these aromatic compounds as unique sources of carbon was investigated by gas chromatography (GC). For this purpose, a method based on the use of GC with flame ionization detection was developed and validated. Validation was carried out in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, precision and trueness. In the case of naphthalene, LOD and LOQ values of 0.43 and 0.72 mg kg(-1) were achieved. Linearity was established over one order of magnitude in the range of interest, i.e. 10-100 mg kg(-1). Excellent precision was obtained both in terms of intra-day repeatability and between-day precision on two concentration levels (RSD% lower than 0.5%). A recovery of 97.9 +/- 0.2% (n=3) was calculated by addition of 640 mg kg(-1) of naphthalene to the Bushnell & Haas mineral salts basal solution containing the micro-organisms. Findings clearly showed a reduction of the naphthalene content equal to 50% and 75% after two and four weeks of contact with the micro-organisms, whereas a lower degradation was shown in the case of toluene. Finally bioremediation activity was ascribed to two different microbial populations, Bordetella Petrii and Bacillus Sphericus, which survived in the polluted medium.


Accelerating seminumerical Fock-exchange calculations using mixed single- and double-precision arithmethic.
We investigate the applicability of single-precision (fp32) floating point operations within our linear-scaling, seminumerical exchange method sn-LinK [Laqua et al., J. Chem. Theory Comput. 16, 1456 (2020)] and find that the vast majority of the three-center-one-electron (3c1e) integrals can be computed with reduced numerical precision with virtually no loss in overall accuracy. This leads to a near doubling in performance on central processing units (CPUs) compared to pure fp64 evaluation. Since the cost of evaluating the 3c1e integrals is less significant on graphic processing units (GPUs) compared to CPU, the performance gains from accelerating 3c1e integrals alone is less impressive on GPUs. Therefore, we also investigate the possibility of employing only fp32 operations to evaluate the exchange matrix within the self-consistent-field (SCF) followed by an accurate one-shot evaluation of the exchange energy using mixed fp32/fp64 precision. This still provides very accurate (1.8 µEh maximal error) results while providing a sevenfold speedup on a typical "gaming" GPU (GTX 1080Ti). We also propose the use of incremental exchange-builds to further reduce these errors. The proposed SCF scheme (i-sn-LinK) requires only one mixed-precision exchange matrix calculation, while all other exchange-matrix builds are performed with only fp32 operations. Compared to pure fp64 evaluation, this leads to 4-7× speedups for the whole SCF procedure without any significant deterioration of the results or the convergence behavior.


Expression of vaspin in the joint and the levels in the serum and synovial fluid of patients with osteoarthritis.
The aim of this study was to determine the expression of vaspin in the joint and investigate the distribution between paired serum and synovial fluid (SF) in osteoarthritis (OA) patients, and serum in healthy controls. The gene expression of vaspin was measured by quantitative real-time polymerase chain reaction (qPCR) in the OA joint tissues. The vaspin protein expression in the cartilage, synovium and osteophyte from OA patients who required total knee replacement (TKR) were detected by immunohistochemistry (IHC). Levels of vaspin in serum and SF were analyzed by enzyme-linked immunosorbent assay (ELISA), including 26 OA patients and 23 healthy controls. All the joint tissues including cartilage, synovium, meniscus, infrapatellar fat pad and osteophyte from OA patients expressed vaspin messenger RNA (mRNA), and the expression of vaspin protein was observed in OA cartilage, synovium and osteophyte. Furthermore, serum vaspin was reduced in OA patients compared to healthy controls, and serum vaspin levels from OA patients exceed those in the paired SF. Serum or SF vaspin were not related to age, gender, or body mass index (BMI). These results suggest that vaspin may be involved in the pathophysiology of OA and may have local effects in the joint during the process of OA.


Nonspecific elicitation of antibody-forming cells in the mouse spleen by bacterial lipopolysaccharide.
Mechanisms of nonspecific elicitation of anti-sheep erythrocyte (SRBC) hemolytic antibody plaqueforming cells (PFC) in mouse spleens with an injection of bacterial endotoxin (lipopolysaccharide (LPS)) were studied in comparison with the genesis of naturally occurring "background" PFC in normal mouse spleens and of rapidly arising PFC in mouse spleens after immunization with SRBC. The cytokinetic pattern of anti-SRBC PFC response after an injection of LPS was quite different from that of the response elicited after immunization with SRBC. In addition, even though LPS nonspecifically elicited anti-SRBC PFC response in mice, LPS could not confer any immunological memory on mouse immunocytess for a "secondary-type" anti-SRBC PFC response to restimulation with LPS or SRBC. The administration of rabbit anti-mouse thymocyte immunoglobulin or anti-SRBC antiserum in mice markedly suppressed the PFC response after immunization with SRBC, but did not do so after stimulation with LPS. Neonatally thymectomized mice could still respond to stimulation with LPS, producing anti-SRBC PFC in their spleens. Injections of actinomycin D or cyclophosphamide into mice resulted in obvious reductions of the PFC responses elicited by either LPS or SRBC. However, injections of these immunosuppressive antisera or drugs did not affect the number of anti-SRBC PFC in normal mouse spleens. These results suggest that the genesis of anti-SRBC PFC developed under different conditions, i.e., background PFC, LPS-stimulated PFC, and antigen-stimulated PFC, are quite different from each other, and that the nonspecific elicitation of anti-SRBC PFC by LPS does not require the helper function of T lymphocytes. No obvious difference, however, was observed in the time of ontogenic maturation among these three different anti-SRBC PFC in the mouse spleens judging from when they were first manifested after birth.


Proteomic analysis of human blood serum using peptide library beads.
Human serum is thought to contain key information for diagnostics of human disease. However, no single technology is currently nor might ever be available to cope with the complexity and dynamic range of the serum proteome. We here report a large-scale proteomic study of human blood serum using peptide library beads and mass spectrometry. Serum proteins are adsorbed onto polymeric beads coated with a combinatorial library composed of millions of hexameric peptide baits. Analysis of the eluates from this combinatorial library (as obtained with 3 eluants of different strength, able to release 99% of the retentate) via liquid chromatography coupled to high-resolution mass spectrometry resulted in the identification of 1559 proteins or 3869 proteins, respectively, depending on how 95% confidence was estimated. In either case, the analysis showed that ligand beads are able to capture a large number of proteins in a single operation. The ligand bead bound fraction appeared to have a lower dynamic range when compared to the starting material, due to a "normalization" of the protein concentrations in the original mixture. We find that extensive information on the protein composition of complex samples such as serum can be obtained using ligand beads and that these beads enrich the proteomic tool box.


Clinicopathologic, immunophenotypic, and immunogenotypic analyses of immunoblastic lymphadenopathy-like T-cell lymphoma.
Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is a distinct peripheral T-cell lymphoma, which closely resembles angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and/or IBL, but is characterized by focal or sheet-like proliferation of immunoblasts and pale cells of T-cell nature. In this report, 36 patients with IBL-like T-cell lymphoma were analyzed. The disease is clinically characterized by generalized lymph node swelling, hepatosplenomegaly, fever, skin rash, polyclonal hypergammaglobulinemia, marked male predominance, predilection for the elderly, and poor prognosis. There was no association with human T-cell leukemia virus type I or human immunodeficiency virus. IBL-like T-cell lymphoma may be divided into two categories (CD4+ type and CD8+ type) by surface marker analysis. It can also be divided into three categories on the basis of the histologic findings of distribution of morphologically recognizable tumor cells: nine cases of "inconspicuous type," six cases of "patchy type," and 21 cases of "diffuse type." Two cases of "inconspicuous type" converted later to "diffuse type." DNA hybridization analyses in the ten recent cases revealed that three of four "inconspicuous types" and five of six "diffuse types" showed clonal rearrangement of T-cell receptor-beta chain gene without rearrangement of immunoglobulin heavy chain gene, providing strong evidence for clonal proliferation of T cells.


Regulation of RKIP function by Helicobacter pylori in gastric cancer.
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells.


[Reliability of Amplicor Mycobacteria test for detection of Mycobacterium tuberculosis complex. M. avium and M. intracellulare: a cooperative study among 9 laboratories].
The Amplicor Mycobacteria, a PCR-based assay, is a rapid test for the detection of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare in clinical samples. To estimate the reliability and reproducibility of the method, a cooperative blind study was conducted among 9 laboratories. Materials used for testing consisted of 105 sputum and 30 water samples containing known numbers of M. bovis BCG, M. avium, M. intracellulare, and samples without bacteria. Only 2 out of the 9 laboratories correctly identified the presence or absence of mycobacterial DNA in all 135 samples. In sputum samples, 6 out of the 9 laboratories detected mycobacterial DNA in all positive samples, and 4 out of the 9 laboratories correctly reported the absence of DNA in the negative samples, indicating the need for good laboratory practice and development of reference reagents to monitor the performance of the whole study, including pretreatment of clinical samples. The main problem was lack of specificity rather than lack of sensitivity. From about half of the laboratories, false-positive results were reported, however, the ratio was below 6%; 1% (1/106 sputum samples) in 3 laboratories, 1.9% (2/105) in 2 laboratories, and 5.7% (6/105) in one laboratory, respectively. These results indicate that the Amplicor Mycobacteria is quite useful for a rapid diagnosis of tuberculosis.


Antegrade administration of mitomycin gel for upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi-institutional retrospective cohort study.
To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow-up of 13.0 months post induction. Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.


Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer.
To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ(2) test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ(2) test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.


Cardamom (Elettaria cardamomum) perinatal exposure effects on the development, behavior and biochemical parameters in mice offspring.
Cardamom is a strong antioxidant plant, so it is called the queen of spices. In the present study, we explored the potentials of cardamom on developmental, learning ability and biochemical parameters of mice offspring. Thirty pregnant mice were allocated to three groups of ten animals in each. Groups Π and Ш received pilsbury's Diet containing 10 and 20% of cardamom (w/w) respectively, whereas Group I used as control. Cardomom was administered from the first day of pregnancy and was continued until post-natal day 15 (PD 15) and thereafter the mothers were switched to plain pilsbury's Diet. During the weaning period, three pups in each litter were color marked from the others, and were subjected to various tests (Physical assessment such body weight and eye opening and hair appearance; the neuromaturation of reflexes like righting, rotating, and cliff avoidance reflexes; learning ability and memory retention; estimation of monoamines neurotransmitters like dopamine and serotonin, non-enzymatic oxidative stress such as TBARS and GSH in forebrain at different ages of pups). The results indicated that the body weight gain was declining significantly. Hair appearance and eyes opening were delayed significantly. Righting, rotating, and cliff avoidance reflexes were delayed in treated animals. Exposure to cardamom led to enhance learning and memory retention as compared to control. Monoamines (DA, 5-HT) and GSH were elevated, whereas TBARS was inhibited significantly. In conclusion, perinatal cardamom exposure enhanced learning and memory as compared to control. Cardamom and its benefit compounds were transported via placenta or/and milk during lactation. Cardamom needs more researches to investigate its benefits on other kinds of behavior.


Multiple domains for the chicken cellular sequences homologous to the v-ets oncogene of the E26 retrovirus.
We have investigated the structure of chicken genomic DNA homologous to v-ets, the second cell-derived oncogene of avian retrovirus E26. We isolated a c-ets locus spanning ca. 30.0 kilobase pairs (kbp) in the chicken genome with homologies to 1,202 nucleotides (nt) of v-ets (total length, 1,508 nt) distributed in six clusters along 18.0 kbp of the cloned DNA. The 5'-distal part of v-ets (224 nt) was homologous to chicken cellular sequences contained upstream within a single 16.0-kbp EcoRI fragment as two typical exons but not found transcribed into the major 7.5-kb c-ets (or 4.0-kb c-myb) RNA species. Between these two v-ets-related cellular sequences we found ca 40.0 kbp of v-ets-unrelated DNA. Finally, the most 3' region of homology to v-ets in the cloned DNA was shown to consist of a truncated exon lacking the nucleotides coding for the 16 carboxy-terminal amino acids of the viral protein but colinear to one of the two human c-ets loci, c-ets-2.


Genotype-phenotype correlation and pregnancy outcomes of partial trisomy 14q: A systematic review.
Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about the human genome have drastically enhanced our ability to detect chromosomal abnormalities prenatally. Despite that, genotype-phenotype correlation is difficult to establish for many chromosomal aberrations, particularly for those that are rare, as it requires thorough analysis of a significant number of cases. This in turn increases the burden of the obstetric provider to appropriately counsel a patient regarding prognosis and pregnancy options in these complicated situations. Our experience in prenatal diagnosis and management of a fetus with multiple anomalies and partial trisomy for the 14q11-q24.2 prompted a comprehensive analysis of the relevant literature. Although complete non-mosaic trisomy 14 is associated with first trimester miscarriages, partial trisomy 14q is a rare condition with undefined genotype-phenotype correlation, preventing accurate prenatal counseling, and informed decision making. We performed a systematic literature review, that aimed to summarize prenatal and postnatal findings of individual case reports on 51 patients with partial trisomy 14q in order to elucidate genotype-phenotype correlation, and to supply healthcare professionals with recommendation on essential fetal and parental testing for accurate diagnosis, pregnancy outcomes, and proper family counseling. Comparison of the clinical findings among the patients with partial 14q trisomy suggest that the resulting phenotype is likely to be influenced by the extent of the 14q trisomy segment, associated chromosomal imbalances, parental origin of the rearrangement, and dosage of the genes within the imprinted 14q32 cluster. © 2016 Wiley Periodicals, Inc.


Experiences of trust in mothers of hospitalized children toward pediatric nurses.
Trust is an essential component of qualified nursing care and correlated with mothers' satisfaction during child's hospitalization. This exploratory qualitative study was conducted to gain a better understanding of trust from mothers of hospitalized children toward pediatric nurses. Data were collected using semi-structured, in-depth interviews with eight mothers with recently hospitalized children. Collected data were analyzed using thematic analysis. As a result, three themes were identified from this study: "assessing the trustworthiness of pediatric nurses," "overcoming emotional burden caused by the child's hospitalization," and "newly recognizing the importance of pediatric nurses." Seven sub-themes were identified. Mothers reported guilt and stress due to their responsibility as the primary caregiver when children were hospitalized. However, mothers felt empowered and gained confidence when trusting pediatric nurses, recognizing their importance, and accepting their help. The result highlights the essential nature of the mother's trust in pediatric nurses, which in turn facilitated emotional support and empowerment for the mothers. Based on this study's insights into the unique experiences of trust from mothers of hospitalized children, pediatric nurses can explore strategies to facilitate trust-building. Based on these findings, pediatric nurses can develop trust-building strategies, tools to assess the level of trust, and interventions to facilitate trust-building.


Preferences of patients receiving bisphosphonates--how to influence the therapeutic adherence.
Therapeutic adherence determines the efficacy of treatments in the clinical practice. Especially in chronic asymptomatic diseases large differences exist between therapeutic success in clinical studies and clinical practice. The treatment of osteoporosis using bisphosphonates is considerably influenced by the low adherence of patients due to the complicated drug application. The VIVA study analyzed the preferences of 1635 patients with osteoporosis in Slovakia using a simple questionnaire. The majority of patients--76% preferred the monthly regime of bisphosphonate therapy, 22% of patients preferred the weekly regimen and only a minority--2% preferred daily application. The results are in agreement with results of the BALTO study in the USA and the SWIFT study in Switzerland showing a clear preference to the monthly regime. The preferences of patients were motivated by various different aspects of improved quality of life, which is offered by the new bisphosphonate regimen once monthly.


[Outflows of trihalomethane precursors from soils].
Outflows of trihalomethane formation potential (THMFPs) which was chosen as an index of the amount and reactivity with chlorine of THMs precursors from soils were studied with soil column experiment. The results indicated that factors influencing THMFP concentrations of leacheates were the physicochemical properties of soils, especially contents, composition and reactivities with chlorine of humic substances, the pH value of feed solution and cumulative leaching volume. The THMFP concentrations of leachates rose with increases in amounts of humic substances with high solubility as well as reactivity with chlorine. The effluents of soil samples contained the lowest THMFP concentrations under the feed solution of the lowest pH value (pH 3.0). THMFPs appeared to more easily flow out from soils with the feed solution of lower pH value, which was properly due to the increases in solubility of humic substances under the lower pH value conditions. In most cases, THMFP concentrations of leachates showed decline with the increase of cumulative leaching volumes of feed solution.


Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease.
There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI. Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006. Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development. MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD.


Hepatitis during respiratory syncytial virus infection--a case report.
Respiratory syncytial virus (RSV) infection is the most common cause of hospitalization in infants and small children. The aim was to present a 13-months old boy diagnosed with acute airway infection, acute otitis media (AOM) and hepatitis during the RSV-infection. Serum catalytic activities of alkaline phosphatase (ALP), aspartate aminotranspherase (AST), alanine aminotranspherase (ALT), gamma glutamyl transpherase (GGT), lactate dehydrogenase (LD), and concentrations of bilirubin were monitored during hospitalization and at control examination. The child had clinical signs and symptoms of respiratory failure, AOM, and laboratory findings of virus infection and liver disease. On admission, catalytic activities of enzymes were markedly increased, especially the activity of ALP (10333 U/L, i.e. 24-fold increase in comparison with the upper reference limit). The highest increased in AST (339 U/L, 4.5-fold), ALT (475 U/L, 10.3-fold) and LD (545 U/L, 1.5-fold) were registered on the 3rd day, and the highest increase in GGT (68 U/L, 3.1-fold) occurred on the 11th day. Seven weeks after discharge AST, ALT, GGT and LD decreased into reference range, and ALP remain mildly increased (478 U/L, 1.1 fold increase). RSV was confirmed in nasal lavage fluid. Laboratory results in patient with RSV infection needs to be interpreted in the light of both, respiratory and extrapulmonary manifestations of the infection, respectively.


Subacute Oral Toxicity of Yukmijiwhang-Tang in Crl:CD Sprague-Dawley Rats and Its Cytotoxicity.
Background. The traditional herbal formula Yukmijiwhang-tang (YMJ) consists of six medicinal herbs and has been used to treat dysuria, diabetic mellitus, and neurosis in Korea, China, and Japan. Here we report safety information on its subacute toxicity and the cytotoxicity. Methods. YMJ extract was administered to SD rats at various dosages for 4 weeks. We monitored clinical signs, mortality, body and organ weights, food intake, and hematological and serum biochemistry factors. For cytotoxicity testing, each cell line was treated with various concentrations of YMJ for 24 h. Results. YMJ treatment had no significant effects on changes in clinical signs, body weight, or food intake in male or female rats. In male rats, YMJ treatment decreased the absolute weights of the epididymides and serum Na levels. In female rats, YMJ significantly reduced the prothrombin time (PT) and serum creatine level. However, the changes were not severe and were considered to be in the normal physiological range for rats. The no-observed-adverse-effect-level (NOAEL) was estimated to be 2000 mg/kg/day. YMJ extract did not exert any cytotoxicity against 23 tested cell lines. Conclusions. Our data provide scientific evidence on the safety of YMJ for potential development as a prescription drug.


A review of skin disease in military soldiers: challenges and potential solutions.
Introduction: Military soldiers comprised 1,195 million United States active-duty members and 778,000 reserve members in 9/2021. Soldiers are often exposed to drastic climates, environments, and living conditions which may make them more susceptible to cutaneous diseases.Methods: A PubMed search of studies published between 1/1/2002 - 8/30/2022, using MeSH terms: ((("Military Personnel"[Majr]) OR "Military Hygiene"[Majr])) OR "Military Medicine"[Majr]) AND "Skin Diseases"[Majr]), the reference lists of select articles, and other applicable sources were reviewed to identify articles on skin conditions affecting military soldiers and treatment options.Discussion: In this article, we review skin conditions that affect military soldiers in both the deployed and non-deployed settings including infectious diseases, arthropod associated diseases, sexually transmitted infections, ultraviolet radiation related skin disease, acne, diseases of hair and hair follicles, dermatitis, onychocryptosis, and conditions caused by extreme weather conditions and occupational exposures. We also discuss treatment options and prevention methods as they relate to military settings.Conclusion: Dermatological conditions can considerably impact soldiers' wellbeing and military performance, often lead to evacuation of military personnel, and are associated with high financial costs. Cutaneous disease is one of most common reasons for soldiers to seek medical care and may cause significant morbidity. Serving in the military often impacts and limits treatment options.


Postural Changes on Heart Rate Variability among Older Population: A Preliminary Study.
This study aims to investigate an association between body postures and autonomic nervous system (ANS) responses through analysis of short-term heart rate variability (HRV) data obtained through electrocardiography. Forty older individuals were recruited to form the sample. HRV measurements were taken in three positions-sitting, supine, and standing-and compared. Results demonstrated statistically significant differences in the HRV parameters used to examine the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS), specifically in the measurements obtained from the sitting position and the supine position (P < 0.001 for PNS and P = 0.011 for SNS). The differences in these parameters were, however, negligible between the sitting and the standing positions. Moreover, the ANS responses obtained in the sitting position were strongly and positively correlated with those in the standing position (r = 0.854 for PNS and r = 0.794 for SNS). These results suggested that the PNS and SNS parameters obtained while sitting were likely to be affected by orthostatic hypotension in much the same way as those in the standing position, as compared to the supine position. As such, sitting may not be the best position for older individuals in the assessment of their autonomic responses, whereas the supine position is recommended as the baseline posture in the old-age population. These findings are useful for future research in clinical settings that require accuracy in the ANS responses as determined by the HRV measurements.


Rectus-sparing approach to the periacetabular osteotomy in adolescents preserves hip flexion strength.
The classic periacetabular osteotomy (PAO) approach can result in hip flexor weakness in adolescents. The rectus-sparing approach (PAO-RS) preserves the origin of the rectus femoris tendon which may prevent hip flexor weakness and improve functional outcome. This is a prospective analysis of adolescents treated with a PAO or PAO-RS. The PAO group included 24 hips/21 patients (18 female, meanage 16 years (sd 4)); the PAO-RS group included ten hips (eight female, mean age 16 years (sd 1)). Preoperatively, the PAO group had decreased hip flexion strength compared with the PAO-RS group (83 Nm/kg versus 102 Nm/kg). A subset of PAO patients (n = 13 hips/12 patients, nine female, mean age 15 years (sd 3)) were matched for preoperative flexion strength to the PAO-RS group. Radiographic parameters, modified Harris hip score (mHHS), isokinetic hip strength and instrumented motion analysis preoperatively, six months and one-year postoperatively were compared. There were no differences in preoperative deformity, postoperative correction or degree of correction between groups. Hip flexor strength decreased significantly at six months in the PAO group compared with the PAO-RS group (-35 Nm/kg versus -7 Nm/kg; p = 0.012), as did hip flexion pull-off power (1.33 W/kg PAO versus 1.76 W/kg PAO-RS; p = 0.010). Hip flexion strength improved from six months to one year in the PAO group, with no significant differences in strength at one year between groups (80 Nm/kg versus 90 Nm/kg). There were no differences between groups in mHHS any time point; both groups improved significantly postoperatively. Preserving the rectus femoris may lead to improved short-term hip flexor strength and pull-off power. Further assessment at long-term follow-up is needed to determine if this strength leads to improved functional outcomes. II.


Lucio phenomenon with concomitant necrotizing fasciitis and acute kidney injury.
Lucio phenomenon is a rare vasculopathy that can occur in patients with Hansen disease, particularly diffuse lepromatous leprosy. It is characterized by retiform purpura and necrotic ulcerations, most commonly affecting the extremities. Diagnosing Lucio phenomenon can be challenging, especially when secondary bacterial infections occur. We report a patient with Lucio phenomenon who presented with acute necrotizing fasciitis of his left upper extremity and a 10-year history of chronic ulcerations. Shortly following admission, he also developed acute kidney injury. The necrotizing fasciitis was treated with prompt surgical debridement and intravenous antibiotics. Biopsy and PCR of a right upper extremity ulcer confirmed the presence of Mycobacterium lepromatosis. Multidrug therapy and prednisone were used to treat the Lucio phenomenon. After initiating treatment, no new lesions developed, kidney function improved, and the patient underwent successful skin graft of his left upper extremity. Although corticosteroid use is controversial, our patient's marked response to multidrug therapy with prednisone highlights the importance of this regimen in severe presentations of Lucio phenomenon. To the best of our knowledge, only two other cases of Lucio phenomenon confirmed to be caused by M. lepromatosis have been reported in living patients (rather than retrospectively identified post-mortem), underscoring the importance of the presented clinical course and treatment regimen.


Where do moral decisions come from?
[Mark] Johnson asks us to take seriously theory as an imaginative construction that offers, not an objective account of the world, but a dynamic, intersubjective construal of it....A common feature [of the four books discussed] is the conviction that moral universals are somehow bound up with dynamic processes that have their origin in the human form, not with disembodied rules or rational arguments per se.


Anomalous nonlinear absorption in epsilon-near-zero materials: optical limiting and all-optical control.
We investigate nonlinear absorption in films of epsilon-near-zero materials. The combination of large local electric fields at the fundamental frequency and material losses at the harmonic frequencies induce unusual intensity-dependent phenomena. We predict that the second-order nonlinearity of a low-damping, epsilon-near-zero slab produces an optical limiting effect that mimics a two-photon absorption process. Anomalous absorption profiles that depend on low permittivity values at the pump frequency are also predicted for third-order nonlinearities. These findings suggest new opportunities for all-optical light control and novel ways to design reconfigurable and tunable nonlinear devices.


Usefulness of Tumor Tissue Biopsy for Predicting the Biological Behavior of Hepatocellular Carcinoma.
Assessment of the biological behavior of tumors is important for choosing an appropriate cancer therapy. In hepatocellular carcinoma (HCC), the biological behaviour can be assessed by tumor morphology and molecular biology. This study investigated the usefulness of tumor tissue biopsy for predicting the biological behavior of HCC. We studied 43 patients who underwent hepatectomy and preoperative liver tumor biopsy for HCC. We performed clinicopathological and immunohistochemical (IHC) analyses. The expression of the following molecules was examined: regulator of G-protein signaling 5 (RGS5), glypican-3 (GPC3), keratin 19 (K19), epithelial cell adhesion molecule (EpCAM), protein induced by vitamin K absence or antagonist-II (PIVKA-II), β-Catenin, and p53. There was an overall 83.7% agreement regarding tumor differentiation between the preoperative biopsy specimens and the resected specimens. The accuracy of IHC analysis was more than 70% for all molecules between the preoperative biopsy specimens and the resected specimens. The RGS5-positive biopsy cases had higher serum α-fetoprotein levels (p=0.04), a higher rate of moderately or poorly differentiated tumors (p=0.02) and portal vein invasion (p=0.0003) than the RGS5-negative biopsy cases. The GPC3-positive biopsy cases were younger (p=0.04), had higher serum PIVKA-II levels (p=0.01), and a higher rate of portal vein invasion (p=0.03) than the GPC3-negative biopsy cases. The PIVKA-II-positive biopsy cases had significantly higher serum PIVKA-II levels than the PIVKA-II-negative biopsy cases (p=0.02). The other molecular markers showed no significantly different clinical findings between the positive and negative cases. In HCC, there was a high agreement rate of both the histopathological and IHC findings between preoperative biopsy specimens and resected specimens. In the biopsy specimens of HCC, RGS5 and GPC3 expression were useful molecular makers for predicting portal vein invasion. Liver tumor biopsy is useful for predicting the biological behavior of HCC through histopathological and immunohistochemical findings.


Association between the neutrophil-to-lymphocyte ratio and obstructive sleep apnea: a meta-analysis.
This meta-analysis is aimed to investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and obstructive sleep apnea (OSA). The PubMed, Web of Science, Google Scholar, and Cochrane Library databases were searched to collect all relevant articles. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated using the random effects model. In addition, subgroup analysis and meta-regression analysis were performed. Eleven eligible articles containing 2,259 patients with OSA were included in this study. Pooled outcomes revealed that the NLR was significantly higher in patients with OSA than in controls (SMD 0.62, 95% CI 0.29-0.94, P = 0.002). In subgroup analyses, differences in the NLR between patients and controls increased with worsening OSA grades. Furthermore, meta-regression analysis showed that differences in mean BMI exerted a significant effect on differences in the NLR (P = 0.0003). In summary, our meta-analysis demonstrated that the NLR in OSA patients was significantly higher than that in controls, and the difference was larger in patients with severe OSA. These results indicate that the NLR may be a reliable marker for detecting systemic inflammation and predicting disease severity in patients with OSA.


Development of Magnetic Resonance-based Functional Imaging: The Past, the Present, and the Future.
The term "theranostics" is a compound word combining "therapeutics" and "diagnostics". Discovery of the X-ray made an extraordinary contribution to the field of medical science. Development of computer science after World War II has been absolutely imperative for the development of medical imaging technology to date. The invention of X-ray computed tomography (CT) has revolutionized medical image diagnostic systems. Several functional imaging modalities emerged not only in the radiological field but also in magnetic resonance and ultrasonic fields. The fusion of three digital imaging techniques, MR Redox imaging, electron paramagnetic resonance (EPR) oxygen mapping, and hyperpolarized (13)C MRI techniques in the magnetic resonance field, contribute to the newly-termed theranostics. Future development of a suitable contrast agent for each imaging modality will be a key for the success of theranositics.


Amino acid sequence of an active fragment of potato proteinase inhibitor IIb.
The amino acid sequence of an active fragment of potato proteinase inhibitor IIb was determined by the Edman degradation procedure and the carboxypeptidase technique. Analyses were carried out on peptides derived from the reduced and carboxymethylated active fragment by digestion with trypsin and chymotrypsin. The active fragment consisted of a single polypeptide chain of 40 amino acid residues including 6 half-cystine residues. Degradation of the intact active fragment by trypsin and subtilisin at pH 6.3--6.4 yielded 3 cystine-containing peptides, and sequence analyses of these peptides revealed that the three disulfide linkages are located between Cys(2) and Cys(16), Cys(6) and Cys(28), and Cys(12) and Cys(38). The reactive site peptide bond of inhibitor IIb, a Lys-Ser bond, is located between positions 26 and 27. The overall sequence of the active fragment is compared with that of an active fragment of inhibitor IIa and the "structure-specificity" relationships of both are discussed. Correlation of the fragments to a naturally-occurring low molecular weight inhibitor is also discussed.


Synagis: an anti-RSV monoclonal antibody.
Palivizumab is a new anti-RSV monoclonal antibody product indicated for the prevention of serious lower respiratory tract disease caused by RSV in pediatric patients at high risk of developing RSV disease ("Synagis," 1998). Palivizumab was evaluated in a single, large clinical trial (IMpact) (Connor et al., 1998). In this trial, RSV hospital admissions were reduced by 55% in children 24 months of age with BPD or in infants born prematurely (35 weeks gestation). Additionally, the severity of illness was also reduced as evidenced by a decrease in total days of RSV hospitalization and decreased incidence of RSV intensive care unit admissions. Palivizumab is expensive--with an estimated cost for a season ranging from $3,500-$10,700 per infant, depending on the child's weight and length of RSV season in the area where the child resides. Although palivizumab prophylaxis has been shown to reduce hospital admissions, the cost effectiveness of using this product needs to be formally evaluated. The AAP has provided guidance to determine the best candidates for RSV prophylaxis.


Inhibition of angiogenesis by bleomycin and its copper complex.
The effects of bleomycin (BLM) and its copper complex on embryonic angiogenesis were studied in the chorioallantoic membranes of 4.5-day-old chick embryos. Copper-free BLM inhibited embryonic angiogenesis in a dose-dependent manner, with activity detectable at 1 ng/egg and maximal at 1000 ng/egg. Also, treatment with copper-BLM complex dose-dependently caused inhibition of embryonic angiogenesis in a lower dose range. Since tumor growth is believed to depend on angiogenesis, the present results may indicate that the antiangiogenic activity of BLM is, at least in part, implicated in the antitumor activity of the drug.