Caring for the health of the public: cross sectional study of the activities of UK public health departments.
The relative time spent in different areas of work in public health departments in the UK was assessed by means of a postal questionnaire. Departments spend one third of their time on population health work, this being similar to the amount of time spent on planning health services. Having a planning department in the health authority did not affect the amount of time spent in any area of work. Having a greater number of consultants in the department was associated with a tendency to spend more time on population health and being involved in training was associated with spending less time on planning. Public health departments in the UK are the only part of the health service with responsibility for the broader aspects of public health. Whilst the tensions between medical care and the wider influences upon population health may represent a false dichotomy, public health professionals must maintain a central focus of their work on the wider influences upon population health if balance is to be maintained within the National Health Service.


Using suicide notes to understand suicide among cancer patients: A mixed-method study.
Cancer patients are at risk of suicide. However, no studies have used suicide notes to investigate their expressed reasons for suicide. The objectives of this study were to compare the characteristics between note leavers and non-leavers among cancer suicide cases and to understand the patterns in expressed reasons for suicide using suicide notes. Suicide cases (2012-2017) were identified from the Hong Kong Coroner's Court reports, which provide detailed information as well as the content of suicide notes. Bivariate tests and multiple logistic regression were performed to compare the characteristics of note leavers and non-leavers among suicide cases with cancer. Thematic analysis was performed on suicide notes to extract themes of expressed reasons for suicides by cancer status and age group. Among cancer suicide cases and compared to non-leavers, note leavers were younger, more likely to be male, use non-violent suicide methods, have better housing conditions, and live alone. Suffering from physical disease was a major theme identified among cancer note leavers across all age groups. Young and middle-aged non-cancer note leavers had various themes identified. Physical illness was the major theme for elderly non-cancer note leavers. Cancer note leavers had unique characteristics and suffering from physical illness was the major expressed reason identified in the suicide notes. Healthcare professionals should pay attention to the mental as well as the physical needs of patients. Improving quality of life and regaining control of life are vital for suicide prevention among cancer patients.


Modification of ventricular fibrillation activation patterns induced by local stretching.
We hypothesize that local modifications in electrophysiological properties, when confined to zones of limited extent, induce few changes in the global activation process during ventricular fibrillation (VF). To test this hypothesis, we produced local electrophysiological modifications by stretching a circumscribed zone of the left ventricular wall in an experimental model of VF. In 23 Langendorff-perfused rabbit hearts frequency, time-frequency and time-domain techniques were used to analyze the VF recordings obtained with two epicardial multiple electrodes before, during, and after local stretching produced with a left intraventricular device. Acute local stretching accelerated VF in the stretched zone reversibly and to a variable degree, depending on the magnitude of stretch and the time elapsed from its application. In the half time (5 minutes) of the analyzed period, a longitudinal lengthening of 12.1 +/- 4.5% (vertical axis) and 11.8 +/- 6.2% (horizontal axis) in the stretched zone produced an increase in the dominant frequency (DFr) (15.2 +/- 1.9 versus 18.8 +/- 2.5 Hz, P < 0.0001), a decrease in mean VV interval (63 +/- 8 versus 53 +/- 6 msec, P < 0.001), and an increase in the complexity of the activation maps-with more areas of conduction block and more breakthrough patterns (23% versus 37%, P < 0.01), without significant changes in the percentages of complete reentry patterns (9% versus 9%, ns). Simultaneously, in the nonstretched zone, no variations were observed in the DFr (15.2 +/- 2.1 versus 15.3 +/- 2.5 Hz, ns), mean VV intervals (66 +/- 8 versus 65 +/- 8 msec, ns), or types and percentages of maps with breakthrough (25% versus 20%, ns) or reentry patterns (12% versus 8%, ns). No significant correlation was observed between the DFr in the two zones (R = 0.24, P = 0.40). Local stretching increases the electrophysiological heterogeneity of myocardium and accelerates and increases the complexity of VF in the stretched area, without significantly modifying the occurrences of the types of VF activation patterns in the nonstretched zone.


An evaluation of aerobic and anaerobic sludges as start-up material for microbial fuel cell systems.
The operation of microbial fuel cells (MFCs) seeded with the same quantities of aerobic or anaerobic sludge has been compared. The two sludges consisted of mixed cultures obtained from the aerobic reactor and anaerobic digester, respectively, of a municipal Wastewater Treatment Plant (WWTP). Both the sludges were diluted with their sedimentation supernatant to avoid modifying their metabolism. The results show that the type of sludge has a major impact on the performance of the system. Seeding an MFC with anaerobic acclimated sludge leads to a more rapid start-up of electricity production and the absence of a lag period. In the MFC seeded with anaerobic sludge, the steady-state operation conditions were achieved in less than 10 days, while in the aerobic sludge-seeded MFC more than 20 days were necessary to achieve this regime. The anaerobic sludge also led to better performance of the MFC. Thus, maximum power densities above 300mWm(-2) were obtained for such systems (i.e. two times higher than that achieved with the aerobic sludge-seeded MFC in the same setup). This better performance is a direct consequence of the greater availability of Chemical Oxygen Demand (COD) in anaerobic sludge. However, the performance is not a consequence of the coulombic efficiency in the use of the COD to produce electricity because the aerobic sludge-seeded MFC doubles this figure with respect to the anaerobic sludge-seeded system.


Engagement in Advance Care Planning and Surrogates' Knowledge of Patients' Treatment Goals.
A key objective of advance care planning (ACP) is improving surrogates' knowledge of patients' treatment goals. Little is known about whether ACP outside of a trial accomplishes this. The objective was to examine patient and surrogate reports of ACP engagement and associations with surrogate knowledge of goals. Cohort study SETTING: Primary care in a Veterans Affairs Medical Center. 350 community-dwelling veterans age ≥55 years and the individual they would choose to make medical decisions on their behalf, interviewed separately. Treatment goals were assessed by veterans' ratings of 3 health states: severe physical disability, cognitive disability, and pain, as an acceptable or unacceptable result of treatment for severe illness. Surrogates had knowledge if they correctly predicted all 3 responses. Veterans and surrogates were asked about living will and health care proxy completion and communication about life-sustaining treatment and quality versus quantity of life (QOL). Over 40% of dyads agreed that the veteran had not completed a living will or health care proxy and that there was no QOL communication. For each activity, sizeable proportions (18-34%) disagreed about participation. In dyads who agreed QOL communication had occurred, 30% of surrogates had knowledge, compared to 21% in dyads who agreed communication had not occurred and 15% in dyads who disagreed (P = .01). This relationship persisted in multivariable analysis. Agreement about other ACP activities was not associated with knowledge. Disagreement about ACP participation was common. Agreement about communication regarding QOL was modestly associated with surrogate knowledge of treatment goals. Eliciting surrogates' perspectives is critical to ACP. Even dyads who agree about participation may need additional support for successful engagement.


Life-saving decompressive craniectomy for diffuse cerebral edema during an episode of new-onset diabetic ketoacidosis: case report and review of the literature.
Diabetic ketoacidosis (DKA), a well-known complication of diabetes mellitus, is associated with severe diffuse cerebral edema leading to brain herniation and death. Survival from an episode of symptomatic cerebral edema has been associated with debilitating neurological sequelae, including motor deficits, visual impairment, memory loss, seizures, and persistent vegetative states. A review of the literature reveals scant information regarding the potential surgical options for these cases. The authors present their case in which they used a craniectomy to treat this life-threatening condition. After reportedly suffering nausea and vomiting, a 12-year-old male presented to the emergency room with lethargy and was diagnosed with acute DKA. After appropriate treatment, the patient became comatose. A CT scan revealed diffuse cerebral edema. To decrease intracranial pressure and prevent further progression of brain herniation, a bifrontal decompressive craniectomy with duraplasty was performed. The patient's neurological function gradually improved, and he returned to school and his regular activities with only minimal cognitive deficits. Given the high mortality and morbidity associated with DKA-related edema, we believe decompressive craniectomy should be considered for malignant cerebral edema and herniation syndrome.


[Results and prospects of studying thrombosis formation in ischemic heart disease].
On the basis of own investigations and literary data of recent years the author discusses problems of frequency and location of thromboembolic complications in ischemic heart disease, their pathogenesis, effect on the course of acute myocardial infarction, clinico-laboratory criteria of diagnostics of the intravascular coagulation syndrome, current methods of diagnosis, treatment and prophylaxis.


A call to action: Unpacking the challenges to implementing social sustainability initiatives in a developing country city.
With cities sprawling and populations booming in developing regions, ensuring social sustainability in urban areas has become more urgent. This study investigates the challenges of implementing social sustainability initiatives for cities in developing countries, focusing on Dhaka as a representative city. A mixed-method approach involving structured questionnaire surveys and key informant interviews was used to collect quantitative and qualitative data. The study identified eighteen challenges to implementing social sustainability initiatives in Dhaka city, including a lack of poor urban governance, an inefficient city management system, a lack of political stability, a long delay in the planning approval process, etc. Additionally, experts identified additional challenges that require attention. The study offers empirical evidence to assist government officials, policymakers, and urban planners overcome these challenges and implement social sustainability effectively. To address the identified challenges, the study recommends revisiting the Structure Plan, Urban Area Plan, Detailed Area Plan, and Urban Sector Policy-2011. It highlights the crucial role of community social workers in mitigating specific issues in socially sustainable urban development. Eventually, the study will contribute to the implementation of SDG-11 in the 2030 Agenda for Sustainable Development by bridging the gap between urbanization and socially sustainable cities.


Epigenetic remodeling of the fungal secondary metabolome.
Fungi treated with DNA methyltransferase and histone deacetylase inhibitors exhibited natural product profiles with enhanced chemical diversity demonstrating that small-molecule epigenetic modifiers are effective tools for rationally controlling the native expression of fungal biosynthetic pathways and generating new biomolecules.


In vivo induction of neoplastic growth in nude mouse connective tissue adjacent to xenografted human tumors.
Induction of neoplastic growth of murine stroma cells within the human tumor xenograft was observed after serial passage of CEA and beta 2-microglobulin producing human colonic SLu tumor xenografts in nu/nu BALB/c mice. Mouse tumors within the human tumor xenografts were identified using specific immunohistologic staining techniques for mouse histocompatibility marker or human CEA. These mixed tumors could be distinguished from normal human tumor xenografts by a different relationship between development of the tumor marker in the serum and tumor size. We were able to establish transformed murine cells from human xenografts, either induced by SC injection of 1 X 10(6) tumor cells of the SLu cell line or by human SLu or mammary carcinoma tissue serially passaged in athymic animals. The established human and murine cell lines were characterized by cytogenetic methods. Transformed murine cells were then continuously passaged in tissue culture. The transformed mouse fibroblasts proved to possess tumorigenicity in nude mice. In the case of SLu-derived mouse tumor cells, tumors also developed in the immunocompetent BALB/c mice using 1 X 10(6) to 5 X 10(6) tumor cells for SC transplantation.


DDR2 facilitates hepatocellular carcinoma invasion and metastasis via activating ERK signaling and stabilizing SNAIL1.
Several studies have found that DDR2 is up-regulated in many tumor types and facilitates tumor progression. However, the role of DDR2 in hepatocellular carcinoma (HCC) progression and its downstream signaling pathways remain unclear. DDR2 expression was assessed in several cell lines and 112 pairs of HCC and matched adjacent noncancerous liver tissues. Clinical significance of DDR2 in HCC was analyzed. Phosphorylated DDR2 (p-DDR2) expression was detected by immunoblotting to evaluate its correlation with DDR2. The effect of DDR2 on HCC cell migration and invasion were examined. Cycloheximide chase experiments were performed to detect the half-life of SNAIL1. Moreover, DDR2 expression was detected by immunohistochemistry to evaluate its correlation with SNAIL1. The regulatory effect of DDR2 on ERK signaling, SNAIL1, EMT, MT1-MMP and MMP2 was confirmed by immunoblotting. The effect of type I collagen on DDR2/ERK2/SNAIL1 signaling was assessed. DDR2 was more highly expressed in HCC than in non-HCC tissues. DDR2 overexpression was correlated with clinicopathological features of poor prognosis. Clinical analysis revealed that DDR2 is an independent prognostic marker for predicting overall survival and disease free survival of HCC patients. Overexpression of DDR2 is associated with p-DDR2 amplification. In vitro studies showed that DDR2 facilitates HCC cell invasion, migration and EMT via activating ERK2 and stabilizing SNAIL1. DDR2 can up-regulate MT1-MMP and MMP2 expression through ERK2/SNAIL1 signaling in HCC. Additionally, collagen I can induce DDR2/ERK2/SNAIL1 signaling activation in HCC cells. Our findings suggest that DDR2 plays an important role in promoting HCC cell invasion and migration, and may serve as a novel therapeutic target in HCC.


Distribution of principal values of the 31P NMR chemical shift tensor in phosphate glasses.
The static line shapes of the powder pattern of the 31P nuclear magnetic resonance (NMR) chemical shift (CS) tensor in phosphate glasses can only be explained by using individual distributions parameters for the principal axes. A model is discussed, which assumes a linear dependency of such distributions from the principal values themselves. Furthermore, the influence of such distributions on magic angle spinning (MAS) spectra is investigated.


Prevalence of gallbladder disease in hyperlipoproteinemia.
An analysis of the occurrence of gallbladder disease (ie, cholelithiasis, cholecystitis, cholecystectomy) in 210 consecutive patients with primary hyperlipoproteinemia showed that the prevalence of gallbladder disease was 8%, 18%, and 42% in males with type IIa, IIb, and IV hyperlipoproteinemia, and 22%, 48%, and 72% in the corresponding groups of females. The 40-59-year-old patients were compared to three necropsy series from Malmö, Sweden. The occurrence of gallbladder disease was within normal limits in type IIa and abnormally high in type IV hyperlipoproteinemia. There were no differences with regard to age, body weight, glucose intolerance, or ischemic heart disease between type IV patients with and without GBD. It is suggested that certain forms of disturbances of lipoprotein metabolism are associated with an increased risk for development of gallbladder disease.


The use of acid phosphatase test papers for DNA profiling.
The acid phosphatase (AP) test is a routine assay used to screen casework items for the possible presence of semen. This colour test is carried out on filter paper which is retained after testing. Two-year-old AP test papers were found to contain sufficient DNA for short tandem repeat (STR) profiling. Prior to polymerase chain reaction (PCR) amplification, the DNA was preferentially separated into sperm depleted and sperm enriched cell fractions. The implication of these findings for past and present cases is discussed.


The Gender Gap in Reaching "Old Age" in the Russian Federation: A Regional Approach.
Reaching older age and longevity in later life is determined by health and mortality across the life course. In the case of Russia, the history of high male mortality skews the interaction between population aging and gender. These differentials can be viewed through a spatial lens in order to both understand their causes, and to better determine policy responses, especially in a federal political system. Using alternative conceptualizations of the "boundary to old age", we produce the first estimates of the gender gap in reaching "old age" for all Russian Federal Subjects using 2017 data. We identify some regional differentiations, but uncertainties around the consistency of registration as well as overall heterogeneity mean that clear-cut regional patterns are hard to ascribe. Our analysis shows the highly significant gender gap at the age of "becoming old" in Russia when disaggregated by region. When looking at the regional level and comparing to other countries, the range of male "boundaries to old age" is almost as great as the global range. We argue that when applying alternative "old-age thresholds", this gap represents a more accurate representation of interaction between space, gender, and mortality in Russia. We conclude with policy and research priorities to better understand and ameliorate the drivers of these spatial and gendered inequalities.


Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide, sequential granulocyte-macrophage-colony-stimulating factor and granulocyte-colony-stimulating factor, and scheduled commencement of leukapheresis in 225 patients undergoing autologous transplantation.
Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. After Cy/GM/G, a CD34+ cell yield of at least 2.0x10(6) per kg was achieved in 90.7 percent of patients. Optimal yield (OY; >or=5x10(6) or 10x10(6) CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p<0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p<0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5x10(6) per kg (p<0.001 and p=0.002, respectively). Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP.


Professional development among newly graduated registered nurses working in acute care hospital settings: A qualitative explorative study.
To explore newly graduated registered nurses' perceptions of their work situation and management of nursing care in complex patient situations after 18 months of work experience. Newly graduated registered nurses working in acute care hospital settings play a critical role in providing safe nursing care. An explorative qualitative design, with four focus group interviews with 14 newly graduated registered nurses working in acute care hospital settings. One theme emerged: 'Clarity and security in one's own nursing role despite facing challenges that hinder professional development' and three categories: 'Independency due to one's own efforts and experience', 'Well-functioning teamwork' and 'Challenges in the work situation'. After 18 months in the profession, the nurses were considered to be advanced beginners; at the same time, the most experienced nurses on their respective wards. They found it challenging and need to further develop competences concerning managing and organizing the nursing care of several complex patient situations or new patient groups, as well as supervising novice registered nurses and nursing students. Powerful and urgent action is needed to be taken by national healthcare policymakers as well a hospital and nurse managers to develop long-term strategies to improve working conditions for newly registered graduated nurses.


Isolation of Leishmania tropica from an Ethiopian cutaneous leishmaniasis patient.
Cutaneous leishmaniasis (CL) in the Old World is caused mainly by three species of Leishmania: L. major, L. tropica and L. aethiopica, and sporadically by L. infantum and L. donovani. In Ethiopia, zoonotic cutaneous leishmaniasis, caused by L. aethiopica, is a major public health problem affecting thousands of people in the highlands. By contrast, little is known about the existence and epidemiology of CL due to L. tropica. In this report, we provide the first well-documented case of CL in Ethiopia caused by L. tropica. The patient acquired the infection in Awash valley of the Ethiopian Rift Valley (northeastern Ethiopia), where Phlebotomus sergenti and P. saevus have previously been found infected by L. tropica. Using the isoenzyme electrophoresis technique, the isolate was found to belong to a variant of L. tropica zymodeme MON-71, one of the new zymodemes found in Ethiopia from P. sergenti in the same region so far. The epidemiological implications of the finding are discussed.


Autonomic dysfunction in epilepsy and mitochondrial diseases.
The autonomic nervous system is involved and influenced in patients with epilepsy and mitochondrial diseases in a variety of complex, often multifaceted, mechanisms. Autonomic dysfunction often remains unrecognized due to a lack of attention and awareness under the prominence of other disease symptoms. Recognition of the diverse autonomic manifestations of epilepsy and mitochondrial disease would enhance early diagnosis and appropriate management, ultimately improving quality the of life and reducing morbidity and mortality in the affected patients. In this chapter, we discuss autonomic nervous system dysfunction in children with epilepsy (Part I) and mitochondrial diseases (Part II).


Understanding diabetic foot ulcers. 1: Pathophysiology.
This is the first part of a two-part unit on diabetic foot ulcers. It describes the pathophysiology, risk factors and signs and symptoms of diabetic foot ulcers.


Improved pain management outcomes with continuous infusion of a local anesthetic after thoracotomy.
We sought to determine the effectiveness of an incisional infusion of local anesthetics through a continuous-infusion elastomeric pump for the management of postoperative pain after thoracotomy. We performed a retrospective comparative analysis of 110 patients undergoing thoracotomies between November 1999 and March 2003. Postoperative pain management with a continuous-infusion elastomeric pump providing local anesthetic into the incisional area was compared with a single-shot epidural in combination with continuous local anesthetic infusion and continuous thoracic epidural infusion. Data sources were reviewed for mean narcotic use, pain score, and complications. After thoracotomy procedures, 38 patients received the ON-Q Pain Relief System (I-Flow Corp, Lake Forest, Calif), 32 received the ON-Q device and single-shot epidural infusion, and 40 received continuous epidural infusion. Demographic attributes, including age, body mass index, and sex were similar between the groups. Preoperative American Society of Anesthesiologists status was significantly higher in the ON-Q group compared with that in the other groups (P = .02). Narcotic use and pain scores were significantly reduced in the ON-Q group compared with that in the epidural group at all time points (P < .001). There were no wound-healing complications or infections associated with the use of the pump. A continuous infusion of 0.25% bupivacaine at 4 mL/h through the ON-Q elastomeric infusion pump is a safe and effective adjunct in postoperative pain management after thoracotomy. The use of the ON-Q Pain Relief System results in decreased narcotic use and lower pain scores compared with continuous epidural infusion.


Effects of thyroid deficiency at birth on deoxyribonucleic acid synthesis and deoxythymidine kinase activity in the developing rat brain.
In thyroid deficiency at birth, the endogenous pool sizes of cellular dTTP did not change much in the cerebellum, cerebrum and brain stem at the whole ages studied, but the specific radioactivities of dTTP, at 2 hours after the subcutaneous injection of [3H]-thymidine, apparently increased only in the cerebellum on the 14th and 21st days as compared with the normal controls. The highest rate of DNA synthesis in vivo, expressed in terms of the specific radioactivity ratio of DNA to dTTP, was observed at the four-day-old normal rat cerebellum, and in the thyroid deficiency it appeared to shift between seven and 14 days of age. On the other hand, no apparent effects of thyroid deprivation on the rates of both the cerebrum and brain stem were found. The results suggest that a temporal alteration of DNA synthesis as well as thymidine metabolism occurred by thyroid deficiency was confined to the cerebellum in the early postnatal development of rats. Indeed, cerebellar thymidine kinase activity, related to DNA synthesis, also displayed a concomitant delay in thyroid deficiency to the characteristic age-dependence of DNA synthesis. No significant difference between normal and thyroidectomized rats was revealed in this respect on both the cerebrum and brain stem throughout the experimental periods.


Spatially and temporally resolved thermal imaging of cyclically heated interconnects by use of scanning thermal microscopy.
A scanning thermal microscope with a Wollaston probe was used to investigate the spatial distribution and temporal variation of temperature in interconnect structures subjected to thermal cycling. The probe, utilized in passive temperature sensing mode, was calibrated from 20 degrees C to 200 degrees C using a single-layer aluminum microdevice. Spatial measurements were performed on nonpassivated aluminum interconnects sinusoidally heated by a 6 MA/cm(2) current at 200 Hz. The interconnects were determined to have temperatures that decreased with position from a maximum located at the center of both the interconnect length and width. Time-resolved temperature measurements were performed on the same structures sinusoidally heated by a 6 MA/cm(2) current at 2 Hz. Both the peak-cycle temperature and average-cycle temperature were found to decrease with increasing distance from the center of the width of the interconnects.


Comparison of [82Br]4-bromoantipyrine and [125I]4-iodoantipyrine: the kinetics of exchange reaction and biodistribution in rats.
Kinetics and mechanism of isotope exchange reaction between [82Br]bromide anion and 4-bromoantipyrine (BrAP), and the iodine-bromine exchange reaction between [125I]iodide anion and BrAP were studied. The preparation of [82Br]BrAP followed by exponential exchange law, the kinetics of the exchange reaction is a second-order reaction with an activation energy of 23.3 kcal/mol. The optimal exchange condition for halogen exchange between [125I]iodide and BrAP was by a hydrothermal melt method at 110 degrees C and 5 min reaction time. The partition coefficient at pH 7.0 for IAP and BrAP was 20.9 and 13.5, respectively. However, BrAP, which displayed the lower partition coefficient, showed higher brain uptake in rats than that for IAP (2.0% dose/organ vs 1.74% dose/organ), at 2 min after an i.v. injection.


Computation in gene networks.
Genetic regulatory networks have the complex task of controlling all aspects of life. Using a model of gene expression by piecewise linear differential equations we show that this process can be considered as a process of computation. This is demonstrated by showing that this model can simulate memory bounded Turing machines. The simulation is robust with respect to perturbations of the system, an important property for both analog computers and biological systems. Robustness is achieved using a condition that ensures that the model equations, that are generally chaotic, follow a predictable dynamics.


A starch-based implant as a controlled drug release system: Non-invasive in vivo characterization using multispectral fluorescence imaging.
Solid implants are parenteral depot systems that can provide a controlled release of drugs in the desired body area over a few days to months. Finding an alternative for the two most commonly used polymers in the production of parenteral depot systems, namely Poly-(lactic acid) (PLA) and Poly-(lactide-co-glycolide) (PLGA), is of great importance due to their certain drawbacks. Our previous study showed the general suitability of starch-based implants for controlled drug release system. In this study, the system is further characterized and the release kinetics are investigated in vitro and in vivo by fluorescence imaging (FI). ICG and DiR, two fluorescent dyes with different hydrophobicity serving as a model for hydrophilic and hydrophobic drugs, have been used. In addition to 2D FI, 3D reconstructions of the starch implant were also used to assess the release kinetics in 3D mode. The in vitro and in vivo studies showed a fast release of ICG and a sustained release of DiR over 30 days from the starch-based implant. No treatment-related adverse effects were observed in mice. Our results indicate the promising potential of the biodegradable biocompatible starch-based implant for the controlled release of hydrophobic drugs.


Potential of neuropeptide Y for preventing or treating post-traumatic stress disorder.
There is extensive evidence that NPY in the brain can modulate the responses to stress and play a critical role in resistance to, or recovery from, harmful effects of stress. Development of PTSD and comorbid depression following exposure to traumatic stress are associated with low NPY. This review discusses putative mechanisms for NPY's anti-stress actions. Recent preclinical data indicating potential for intranasal delivery of NPY to brain as a promising non-invasive strategy to prevent a variety of neuroendocrine, molecular and behavioral impairments in PTSD model are summarized.


Two-photon absorption cross-sections and time-resolved fluorescence imaging using porphyrin photosensitisers.
Three porphyrin systems have been characterised for use in two-photon fluorescence imaging of biological samples. We have determined the two-photon absorption cross sections (sigma(2)) of the di-cation, free-base and metallated forms of hematoporphyrin derivative (HpD), hematoporphyrin IX (Hp9) and a boronated protoporphyrin (BOPP) using the open-aperture Z-scan and the two-photon induced fluorescence (TPIF) techniques at an excitation wavelength of 800 nm. The insertion of either protons or a metal ion into the macrocycle is shown not to significantly influence the sigma(2) of the porphyrins. Two-photon time-resolved fluorescence images of C6 glioma cells transfected with a free-base form of the BOPP have been obtained as a function of the porphyrin concentration. These studies reveal a maximum useful porphyrin concentration for fluorescence imaging purposes of approximately 30 microg mL(-1).


Bone morphogenetic protein receptor-II mutation Arg491Trp causes malignant phenotype of familial primary pulmonary hypertension.
A four-generation pedigree of familial primary pulmonary hypertension (FPPH) with 14 alive members was collected. In the family, three of the 14 alive familial members were diagnosed as FPPH. Mutations in bone morphogenetic protein receptor-II (BMPR-II) gene were screened by using sequencing analysis. A C-to-T transition at position 1471 in exon 11 of the BMPR-II gene was identified, resulting in an Arg491Trp mutation. We confirmed segregation of the mutation within the family and excluded the presence of the mutations in a panel of 240 chromosomes from normal individuals. No mutations were found in BMPR-II gene in other 10 patients with sporadic primary pulmonary hypertension. The Arg491Trp mutation is located in the kinase domain and predicted to disturb the kinase activity of BMPR-II. Total 7 familial members died at age 8-45 years with various symptoms, indicating other genetic or environmental modifiers involved in the modification of the clinical phenotype.


Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin.
The mainstay of therapy for RSV disease is supportive care, although aerosolized ribavirin has been used to treat infants and young children with severe lower respiratory tract infections. Aerosolized ribavirin has adverse effects, high cost and teratogenic potential. We report the case of a pediatric liver transplant recipient diagnosed with lower respiratory RSV infection, who was successfully treated with oral ribavirin.


Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells.
Thymalin is a polypeptide complex isolated from the thymus and regulating the functions of the immune system. Thymalin is effective in therapy of acute respiratory syndrome, chronic obstructive bronchitis, and other immunopathology. Thymalin increases functional activity of T lymphocytes, but the targeted molecular mechanism of its biological activity requires further study. We studied the influence of thymalin on differentiation of human hematopoietic stem cells (HSC) and expression of CD28 molecule involved in the implementation of antiviral immunity in COVID-19 infection. It was found that thymalin reduced the expression of CD44 (stem cell marker) and CD117 (molecule of the intermediate stage of HSC differentiation) by 2-3 times and increased the expression of CD28 (marker of mature T lymphocytes) by 6.8 times. This indirectly indicates that thymalin stimulated differentiation of CD117+ cells into mature CD28+T lymphocytes. It is known that in patients with severe COVID-19, the number of CD28+, CD4+, CD8+T lymphocytes in the blood decreased, which attested to a pronounced suppression of immunity. It is possible that the antiviral effect of thymalin consists in compensatory stimulation of HSC differentiation into CD28+T lymphocytes at the stage of immunity suppression in unfavorable course of viral infection. Thymalin can be considered as an immunoprotective peptide drug for the prevention of COVID-19.


A simple assay for the ribonuclease activity of ribonucleases in the presence of ethidium bromide.
The ribonuclease (RNase) activity of ribonucleases has been assayed by observing the change in fluorescence intensity of ethidium bromide on binding with yeast RNA. The binding of EtBr with RNA was monitored via UV-vis and fluorimetric methods. The degradation of RNA by RNase A was monitored by the change in fluorescence emission intensity of ethidium bromide at 600nm on excitation at 510nm. The ribonucleolytic activity of RNase A and angiogenin at various pH values was determined by this method. From this technique we have also determined the macroscopic pKa values of active site residues of these enzymes. This assay permits the evaluation of the catalytic efficiency of enzymatic proteins ranging from high ribonucleolytic activity to low ribonucleolytic activity toward the natural substrate RNA.


Infidelity of leafcutting ants to host plants: resource heterogeneity or defense induction?
Leafcutting ants have strong among- and within-plant preferences, and generally abandon plants long before they are completely defoliated. Two tropical deciduous forest tree species preferred by the leafcutting ant Atta colombica were studied to determine how variation in resource quality affects ant selectivity and partial defoliation of plants. Significant differences in palatability and leaf characteristics of Spondias mombin and Bursera simaruba were found among trees and among leaf types within trees, but not among branches within trees. No short-term responses to experimental defoliation of up to 50% of total canopy were found in either species. Leaf nutrient and poisture content were positively correlated, and phenolic content negatively correlated, with the palatability of Spondias mombin, a species containing hydrolyzable tannins. Leaf moisture and phenolic content were both positively correlated with the palatability of Bursera simaruba, which contains predominantly condensed tannins. The results suggest that variation in leaf quality among and within plants is at least a partial explanation for ant selectivity and partial defoliation of preferred species. There is no evidence that rapidly induced changes in plant chemistry affect ant decisions to abandon these plants. Instead, it appears likely that ants abandon plants once high-quality leaf patches are exhausted. Quantitative variation in leaf nutrients, moisture, and secondary chemicals all appear to contribute to ant preferences for individuals and tissues of highly palatable plants.


Large genome-wide association study identifies three novel risk variants for restless legs syndrome.
Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10-18), rs10068599-T (OR = 1.09, P = 6.9 × 10-10) and rs10769894-A (OR = 0.90, P = 9.4 × 10-14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.


Angiopoietin-1 therapy enhances fibrosis and inflammation following folic acid-induced acute renal injury.
The loss of interstitial capillaries is a feature of several experimental models of renal disease and this contributes to secondary kidney injury. Angiopoietin-1 is a secreted growth factor which binds to Tie-2 present on endothelia to enhance cell survival thereby stabilizing capillary architecture in-vitro. Previous studies showed that angiopoietin-1 prevented renal capillary and interstitial lesions following experimental ureteric obstruction. We tested here the effect of angiopoietin-1 treatment on capillary loss and associated tubulointerstitial damage known to follow recovery from folic acid-induced tubular necrosis and acute renal injury. We found that delivery of angiopoietin-1 by adenoviral vectors stabilized peritubular capillaries in folic acid nephropathy but this was accompanied by profibrotic and inflammatory effects. These results suggest that the use of endothelial growth factor therapy for kidney disease may have varying outcomes that depend on the disease model tested.


Association of cholesteryl ester transfer protein (TaqIB) and apolipoprotein E (HhaI) gene variants with obesity.
Background The pathophysiology of obesity is known to be influenced by alterations in lipid levels. We aimed to evaluate association of cholesteryl ester transfer protein (CETP) and apolipoprotein (APO) E gene variants with asymptomatic obesity. Methods A total of 437 subjects, 159 asymptomatic obese (BMI = 29.29 +/- 3.76) and 278 non-obese (BMI = 23.38 +/- 1.71) individuals, were included in this case-control study. Lipid levels were estimated using standard protocols. Analysis of CETP (TaqIB) and APOE (HhaI) gene polymorphisms was done using PCR-RFLP. Results We found significant difference in blood pressure (systolic, P < 0.0001 and diastolic, P < 0.0001), total cholesterol (P < 0.0001), LDL-cholesterol (P < 0.0001), and HDL-cholesterol (P < 0.0001) in obese as compared to non-obese group. Homozygous APO E4E4 genotype was only observed in 5.7% of obese individuals and none in non-obese group. APO E4 allele carriers were also susceptible for obesity (P = 0.016, OR = 1.73; 95% CI = 1.12-2.68) than non-carriers. Higher blood pressure (Systolic, P = 0.001 and Diastolic, P = 0.004) and triglyceride levels (P = 0.029) were observed in obese subjects with APO E4 allele than individuals without APO E4. However, CETP B1 variant allele carriers did not show alteration in blood pressure and lipid profile in asymptomatic obese subjects. Conclusions APO E4 genotype and allele were found to be associated with asymptomatic obesity, whereas CETP Taq1B polymorphism showed no such association in North Indian subjects.


Probing the nature of black holes: Deep in the mHz gravitational-wave sky.
Black holes are unique among astrophysical sources: they are the simplest macroscopic objects in the Universe, and they are extraordinary in terms of their ability to convert energy into electromagnetic and gravitational radiation. Our capacity to probe their nature is limited by the sensitivity of our detectors. The LIGO/Virgo interferometers are the gravitational-wave equivalent of Galileo's telescope. The first few detections represent the beginning of a long journey of exploration. At the current pace of technological progress, it is reasonable to expect that the gravitational-wave detectors available in the 2035-2050s will be formidable tools to explore these fascinating objects in the cosmos, and space-based detectors with peak sensitivities in the mHz band represent one class of such tools. These detectors have a staggering discovery potential, and they will address fundamental open questions in physics and astronomy. Are astrophysical black holes adequately described by general relativity? Do we have empirical evidence for event horizons? Can black holes provide a glimpse into quantum gravity, or reveal a classical breakdown of Einstein's gravity? How and when did black holes form, and how do they grow? Are there new long-range interactions or fields in our Universe, potentially related to dark matter and dark energy or a more fundamental description of gravitation? Precision tests of black hole spacetimes with mHz-band gravitational-wave detectors will probe general relativity and fundamental physics in previously inaccessible regimes, and allow us to address some of these fundamental issues in our current understanding of nature.


Case Report of a Hemangioblastoma With Large Blood Vessels and Rare Vascular Anomalies: Is It Fibromuscular Dysplasia or Arteriovenous Malformation Association?
Hemangioblastoma is considered a benign neoplasm characterized by abnormal vasculature and stromal cells; several pathophysiological mechanisms have been proposed, such as genetic predisposition, hormonal factors, and arterial wall ischemia. Fibromuscular dysplasia is characterized by hyperplasia or thinning of the smooth muscle, elastic fibre destruction, fibrous tissue proliferation, and arterial wall disorganization. We present a cerebellar hemangioblastoma case not associated with Von Hippel Lindau syndrome. Histologically we evidenced big vessels with anomalies of the vascular walls corresponding to fibromuscular dysplasia, and those changes have not been described in these types of tumors. In this light, rare findings could be called vascular malformations or degenerative vascular changes, fibromuscular dysplasia or vascular anomalies. Arterio-venous malformation and hemangioblastoma pathology are rarely presented together. Notwithstanding, we could say that it is a stromal stem cell tumor in a varied stage of differentiation.


In memoriam Liv Hatle 1936-2023, pioneering echocardiologist.
Professor Liv Hatle died in June 2023. In Trondheim, Norway, in the mid-1970s she was the first cardiologist to be given access to a PEDOF Doppler ultrasound system for clinical examinations, which she used to investigate cardiovascular haemodynamics non-invasively. She went on to establish methods for estimating valve gradients, pulmonary arterial pressure, and left ventricular diastolic function, that are still used today in millions of patients worldwide.


Safety of buccal infiltration local anaesthesia for dental procedures.
To assess the safety of buccal infiltration local anaesthetic (LA) without additional factor replacement in patients with haemophilia (PWH) and association with clinical experience of the operator. A consecutive sample of participants with mild, moderate and severe haemophilia scheduled to have dental treatment were recruited from a comprehensive care centre in Ireland. Infiltration LA was administered using a standard technique. Safety was defined as any adverse event at time of administration, immediate postoperative, or postoperative period. Clinical experience was dichotomized into fewer or greater than three years clinical experience. N = 135 buccal infiltration LAs without additional factor replacement were provided to N = 71 participants with mild (n = 20; 28%) and moderate to severe haemophilia (n = 51; 72%). Successful local anaesthesia was achieved in n = 133 cases (99%). No (0%) adverse bleeding events were recorded for any participants at time of administration of LA or during follow-up. Three out of 135 (2.2%) LAs recorded superficial bleeding 30 seconds after administration of LA, all of which resolved within 2 minutes with application of pressure; 4 out of 135 (3%) LAs produced a superficial haematoma at the site of injection no greater than 2 mm all of which resolved at 4 minutes. There were no differences in bleeding rates between clinicians by level of experience (P = 0.435) or by severity of bleeding disorder (P = 1.0). Local anaesthetic is safe to administer via buccal infiltration for people with mild, moderate and severe haemophilia without additional factor cover. This finding holds true regardless of operator experience.


Characterisation of protein co-extracted together with LPS in Escherichia coli, Salmonella minnesota and Yersinia enterocolitica.
The porin proteins of Escherichia coli, Yersinia enterocolitica, and Salmonella minnesota were found to co-extract by the phenol-chloroform-petroleum ether method together with the R lipopolysaccharide of these strains. Lipopolysaccharide free protein recovered from the phenolic residue of the phenol-chloroform-petroleum ether extract migrated as a Mr 36-37,000 protein. We could demonstrate that the protein was extracted from bacteria as a high molecular weight protein-lipopolysaccharide complex. Once exposed to phenolic conditions, the protein was no longer soluble in the phenol-chloroform-petroleum ether extraction mixture, indicating a highly specific lipopolysaccharide-protein association.


A good catch: packaging the virus genome.
In tailed bacteriophages and herpesviruses, double-stranded DNA is packaged into a pre-existing protein shell, through a dedicated channel known as the portal. In a recent issue of Molecular Cell, Zheng et al. determined the structure of the bacteriophage P22 portal complex in pre- and postpackaging conformations, identifying structural changes that serve to retain the genome within the virus particle and prime it for injection into a new host.


Optimization and calibration of behavioural tests on different species of planaria for ecotoxicological studies.
Freshwater planarian are emerging as a valuable in vivo model for (eco) toxicological studies, but the lack of harmonization of procedures between laboratories remains a challenge. This study aimed to optimize, automate and select the best behavioural tests and analyse the potential of different planarian species as models for toxicological assessment. We implemented four tests: exploration, photomotor response, Tapping and Planarian Light Dark Test, on different planaria species using the DanioVision system. We conclude that the exploration assay performed in 24 well-plate at 10,000 lux is the one that is robust and reliable for toxicological studies with planaria. Dugesia japonica and Schmidtea mediterranea have proved to be sensitive models for toxicological screening of organophosphorus pesticides through behavioural analysis. Under necessary experimental conditions, the motility baseline in controls, for both species allowed the detection of behavioural changes, making both good models for behavioural testing in (eco) toxicological context.


Childhood exposure to war and adult onset of cardiometabolic disorders among older Europeans.
Childhood exposure to contexts of war is a common occurrence among current and recent cohorts of children in various parts of the world. It was also common among older cohorts across Europe. Utilizing the Survey of Health, Ageing, and Retirement in Europe (SHARE) the present study links early life course residential histories with detailed information on the timing and location of hostilities during WWII to address three questions: 1) is childhood exposure to war associated with earlier onset of cardiometabolic disease (cardiovascular disease, hypertension, high cholesterol, and diabetes)? 2) did this additional risk vary depending on the timing of first exposure? 3) did this additional risk manifest via different life course pathways depending on exposure timing? Results demonstrate that exposure to war is associated with increased lifetime risk of cardiovascular disease, diabetes, high cholesterol, and hypertension and that this association is strongly concentrated among cohorts exposed in utero or during early childhood (e.g., before age 8). The results also suggest that the impact of war exposure on cardiometabolic disorders are likely to be direct, operating through latent biological processes rather than through childhood hardship, stunting of adult socioeconomic attainment, or elevated risk-taking behaviors.


[Morphometry using computerized tomography of the wrist in idiopathic carpal tunnel syndrome. Comparison of pre- and postoperative findings].
Alteration of carpal morphometry after surgical release of the carpal tunnel was investigated in 22 patients with idiopathic carpal tunnel syndrome, using pre- and postoperative computed tomography. The morphometric evaluation showed an increase in carpal volume which was due to a palmar soft-tissue prolapse in 90% and to an increase of the carpal arch cross sectional area in about 10%. The carpal tunnel release caused a palmar opening of the canal most commonly at the pisiform bone. There was also a variation in form and an increase in volume of Guyon's canal. The results are discussed and related to the postoperative complaints.


A time sharing cross-sectional study of monolinguals and bilinguals at different levels of second language acquisition.
Several methodological factors associated with the concurrent activities (finger-tapping) paradigm were considered in a cross-sectional study investigating cerebral patterns of asymmetry in three groups of English-speaking non-Hispanic dextral males at three levels of second language (Spanish) acquisition and one control group of monolinguals. Results revealed the fluent bilinguals to be bilateral and significantly different from other groups for native language tasks in English. Moreover, a priori contrasts indicate that greater right- than left-hand disruption in concurrent tapping may be typical of monolinguals, but can be influenced by other factors. Monolingual reliability test-retest correlations were .77 and .47.


An inhibitor of the human UDP-GlcNAc 4-epimerase identified from a uridine-based library: a strategy to inhibit O-linked glycosylation.
The biological study of O-linked glycosylation is particularly problematic, as chemical tools to control this modification are lacking. An inhibitor of the UDP-GlcNAc 4-epimerase that synthesizes UDP-GalNAc, the donor initiating O-linked glycosylation, would be a powerful reagent for reversibly inhibiting O-linked glycosylation. We synthesized a 1338 member library of uridine analogs directed to the epimerase by virtue of substrate mimicry. Screening of the library identified an inhibitor with a K(i) value of 11 microM. Tests against related enzymes confirmed the compound's specificity for the UDP-GlcNAc 4-epimerase. Inhibitors of a key step of O-linked glycan biosynthesis can be discovered from a directed library screen. Progeny thereof may be powerful tools for controlling O-linked glycosylation in cells.


Passive UHF RFID-based Knitted Wearable Compression Sensor.
One of the major challenges faced by passive on-body wireless Internet of Things (IoT) sensors is the absorption of radiated power by tissues in the human body. We present a battery-less, wearable knitted Ultra High Frequency (UHF, 902-928 MHz) Radio Frequency Identification (RFID) compression sensor (Bellypatch) antenna and show its applicability as an on-body respiratory monitor. The antenna radiation efficiency is satisfactory in both free-space and on-body operations. We extract RF (Radio Frequency) sheet resistance values of three knitted silver-coated nylon fabric candidates at 913 MHz. The best type of fabric is selected based on the extracted RF sheet resistance. Simulated and measured performance of the antenna confirm suitability for on-body applications. The proposed Bellypatch antenna is used to measure the breathing activity of a programmable infant patient emulator mannequin (SimBaby) and a human subject. The antenna is highly sensitive to respiratory compression and relaxation. Fluctuations in the backscatter power level/Received Signal Strength Indicator (RSSI) in both cases range from 6 dB to 15 dB. The improved on-body read range of the proposed sensor antenna is 5.8 m, about 10 times higher than its predecessor wearable knitted strain sensing Bellyband antenna (0.6 m). The maximum simulated Specific Absorption Rate (SAR) on a human torso model is 0.25 W/kg, lower than the maximum allowable limit of 1.6 W/kg.


Anterior Chamber Angle and Anterior Chamber Volume in a 40- to 64-Year-Old Population.
To determine the distribution of the anterior chamber angle (ACA) and anterior chamber volume (ACV) in an Iranian population of 40- to 64-year-old people using the Pentacam. In this cross-sectional study, multistage sampling was used to select 300 clusters, including 6,311 individuals from the city of Shahroud. All selected participants underwent examinations in one place. Optometric examinations, including measurement of visual acuity and refraction, and ophthalmologic examinations, including slit-lamp examination, were performed for all participants. Moreover, all patients underwent imaging with the Pentacam. The mean ACA and ACV was 34.3° (95% confidence interval [CI]: 34.1°-34.5°) and 139 μL (95% CI: 137.7-140.3), respectively. In a multiple linear regression model, the ACA was inversely correlated with age (coefficient=-0.08), lens thickness (coefficient=-1.38), corneal diameter (coefficient=-0.36), and corneal curvature (coefficient=-1.43), and directly correlated with the anterior chamber depth (ACD) (coefficient=6.59). In another model, ACV was inversely correlated with age (coefficient=-0.37), central corneal thickness (coefficient=-0.04), and spherical equivalent (coefficient=-1.15), and directly correlated with the ACD (coefficient=85.67), lens thickness (coefficient=14.15), corneal diameter (coefficient=4.80), corneal curvature (coefficient=18.43), ACA (coefficient=0.65), and intraocular pressure (coefficient=0.23). The findings of this study could be used as a reference for diagnosis and treatment in Iran and the Middle East region. Increase in age and decrease in the ACD were important factors associated with decreased ACA and ACV, although the correlation of other biometric components was also evaluated. Some of these components, such as the corneal curvature and lens thickness, had a significant relationship with these two variables.


Malignant giant cell tumor of the skull base originating from clivus and sphenoid bone.
We present a case report of a giant cell tumor located in the skull base orginating from clivus and sphenoid bone treated by surgery and external beam radiotherapy (EBRT).


Effects of titanium surface anodization with CaP incorporation on human osteoblastic response.
In this study we investigated whether anodization with calcium phosphate (CaP) incorporation (Vulcano®) enhances growth factors' secretion, osteoblast-specific gene expression, and cell viability, when compared to acid etched surfaces (Porous®) and machined surfaces (Screw®) after 3 and 7days. Results showed significant cell viability for Porous and Vulcano at day 7, when compared with Screw (p=0.005). At the same time point, significant differences regarding runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and bone sialoprotein (BSP) expression were found for all surfaces (p<0.05), but with greater fold induction for Porous and Vulcano. The secretion of transforming growth factor β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) was not significantly affected by surface treatment in any experimental time (p>0.05). Although no significant correlation was found for growth factors' secretion and Runx2 expression, a significant positive correlation between this gene and ALP/BSP expression showed that their strong association is independent on the type of surface. The incorporation of CaP affected the biological parameters evaluated similar to surfaces just acid etched. The results presented here support the observations that roughness also may play an important role in determining cell response.


Influence of race and socioeconomic status on sleep: Pittsburgh SleepSCORE project.
To examine the independent and interactive effects of race and socioeconomic status (SES) on objective indices and self-reports of sleep. The sleep of 187 adults (41% black; mean age = 59.5 +/- 7.2 years) was examined. Nine nights of actigraphy and two nights of inhome polysomnography (PSG) were used to assess average sleep duration, continuity, and architecture; self-report was used to assess sleep quality. Psychosocial factors, health behaviors, and environmental factors were also measured. Blacks had shorter sleep duration and lower sleep efficiency, as measured by actigraphy and PSG, and they spent less time proportionately in Stage 3-4 sleep, compared with others (p < .01). Lower SES was associated with longer actigraphy-measured latency, more wake after sleep onset as measured by PSG, and poorer sleep quality on the Pittsburgh Sleep Quality Index (p < .05). Blacks and perhaps individuals in lower SES groups may be at risk for sleep disturbances and associated health consequences.


Adhesive Approach Using Internal Coping for Vertical Root Fractured Teeth with Flared Root Canals.
Vertical root fractures are often observed in teeth with endodontic treatment and post space preparation. Frequently, because such teeth have flared root canals with thin dentin walls, conventional treatments are disadvantageous in terms of adhesiveness, sealability and risk of refracture. Here we devised an intentional replantation method that uses internal resin coping, with a reinforcing effect on thin root canal dentin. In two patients treated with this method, satisfactory conditions have been maintained. This report suggests that an intentional replantation method in which an internal resin coping is employed may be a useful therapy for fractured teeth with flared root canals.


Streptavidin functionalized nickel nanowires: A new ferromagnetic platform for biotinylated-based assays.
Herein we present highly stable ferromagnetic nickel nanowires modified with streptavidin (NiNW-STR). This versatile functionalized nanomaterial works as an excellent biosensing platform for the immobilization of a wide range of biotinylated molecules. Moreover, these NWs can be employed in magnetic-based assays. Different proofs-of-concept such as streptavidin-biotin assays and capture of single and double stranded DNA were successfully carried out, corroborating NiNW-STR usefulness. Moreover, repeatability and stability studies were also effectively performed.


Somatic Mutations of PI3K in Early and Advanced Gallbladder Cancer: Additional Options for an Orphan Cancer.
Gallbladder cancer (GBC) is the second-leading cause of death from malignant tumors in Chilean women. The phosphatidylinositol 3-kinase (PI3K) pathway is involved in proliferation, cell survival, and growth. We investigated mutations in exons 9 and 20 of the PI3K gene in GBC. Mutations in exons 9 (E542K, E545G, E545K) and 20 (H1047L and H1047R) of PI3K were determined by direct sequencing in 130 cases of GBC. The patient group consisted of 110 women and 20 men, and mutations were found in 22 cases (16.9%). Of these, 14 cases had mutations in exon 9 (63.6%) (E542K, 64%; E545K, 29%; and E545G, 7%) and 8 in exon 20 (37.4%; H1047L, 50%; H1047R, 50%). No differences were noted in the frequency and type of mutations analyzed by sex, age, or histologic features. We observed mutations in 22% of the early-stage GBC and 14.6% of the advanced cases. In this series of GBC, 17% of cases were noted as having mutations in either exons 9 or 20 of PI3K. These results suggest that therapeutic testing of inhibitors of the PI3K/AKT pathway may be of benefit in advanced GBC patients.


Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments.
To identify the major aggrecanase- and matrix metalloproteinase (MMP)-generated aggrecan fragments in human osteoarthritis (OA) synovial fluid and in human OA joint cartilage. Aggrecan fragments were prepared by CsCl gradient centrifugation. Fragment distributions were compared with aggrecanase-1 (ADAMTS-4) and MMP-3 digested human aggrecan by analysis with neoepitope antibodies and an anti-G1 domain antibody, using Western immuno-blots. The overall fragment pattern of OA synovial fluid aggrecan was similar to the fragment pattern of cartilage aggrecan cleaved in vitro by ADAMTS-4. However, multiple glycosaminoglycan (GAG) containing aggrecanase and MMP-generated aggrecan fragments were identified in OA synovial fluid and some of these fragments were produced by the action of both types of proteinases. The synovial fluid content of large size aggrecan fragments with (374)ARGS- and (342)FFGV- N-terminals was about 107 and 40 pmoles per ml, respectively, out of a total concentration of aggrecan fragments of about 185 pmoles per ml. OA synovial fluid contained insignificant amounts of the G1-IPEN(341) fragment as compared to the G1-TEGE(373) fragment, while OA cartilage contained significant amounts of both fragments. OA cartilage contained several GAG-containing aggrecan fragments with N-terminals of G1- or (342)FFGV- but no fragments with an N-terminal of (374)ARGS-. The overall pattern of aggrecan fragments in human OA synovial fluid and cartilage supports an important role for aggrecanase in aggrecan degradation. However, the fragment patterns and their differential distribution between cartilage and synovial fluid are consistent with the existence of at least two proteolytic pathways for aggrecan degradation in human OA, generating both (342)FFGV- and (374)ARGS-fragments.


An endovascular approach to cardioembolic stroke prevention in atrial fibrillation patients.
This report is of a 62-year-old woman presenting with a 3-year history of chronic atrial fibrillation (AF) and unable to tolerate chronic warfarin therapy due to bleeding episodes and unstable INR values. Additional high risk factors for stroke are a history of congestive heart failure and previous embolic stroke. Percutaneous left atrial appendage transcatheter occlusion (PLAATO ) was performed to seal the LAA. A transesophageal echocardiography (TEE) at the 1- and 6-month follow-up showed no device migration and no new thrombus related to the implant. The patient has been doing well on postprocedure aspirin with no embolic events.


Evaluation of Inappropriate Positioning of Dosimeters in Medical Workers Based on Dose Equivalent Hp(10).
This report presents a new method to characterize the inappropriate positioning of dosimeters based on the dose equivalent Hp(10). The Hp(10) values of medical workers were measured monthly for 12 mo using two personal dosimeters. Using the ratio between the values of Hp(10) recorded from dosimeters worn over and under protective aprons [Hp(10) over and Hp(10) under , respectively], 670 pairs of dosimeter readings were categorized into a proper use group [Hp(10) over /Hp(10) under ≥ 5] and a misuse group [Hp(10) over /Hp(10) under < 5]. Following personal interviews, the readings in the misuse group were classified into the following six subgroups: "reversed," "sometimes reversed," "both under," "both over," "without apron," and "not specified." Ultimately, the scatter plot of "Hp(10) over - Hp(10) under " vs. Hp(10) over was identified as the most promising tool for clarifying the misuse patterns of dosimeters, as individual readings were mapped to the locations of the corresponding subgroups in the obtained graphs. Our results are expected to facilitate efficient and accurate usage of dosimeters by medical workers.


Low birth weight is not associated with clinically overt thyroid disease: a population based twin case-control study.
In recent years low birth weight has been proposed as a risk factor for the development of several chronic diseases in adult life, including diabetes and subclinical autoimmune thyroid disease. The association could, however, also be due to genetic or environmental factors affecting both birth weight and adverse health outcomes in adult life. Moreover, it is at present unknown whether or not low birth weight is associated with an increased risk of developing clinically overt thyroid disease. The aim of the present study was to investigate the impact of birth weight and several other birth characteristics on the development of clinically overt thyroid disease. A twin case-control study of same sex twin pairs. One hundred and thirty-one same sex twin pairs (262 twin individuals) discordant for clinically overt thyroid disease, ascertained from a population based nation-wide twin register. Information about birth weight, birth length, birth order (first vs. second born), and prematurity was obtained from the original midwife records. Forty-nine twin pairs were discordant for clinically overt autoimmune thyroid disease (Graves' disease = 35 and Hashimoto's thyroiditis = 14) and 82 pairs were discordant for overt nonautoimmune thyroid disease (Simple goitre = 79 and toxic nodular goitre = 3). Overall, there was no difference in birth weights between probands and the healthy co-twins in monozygotic (MZ, n = 39) or in dizygotic (DZ, n = 92) pairs (MZ: mean +/- SE: 2619 +/- 93 g vs. 2553 +/- 89 g, P = 0.40; DZ: 2576 +/- 45 g vs. 2585 +/- 49, P = 0.86). By means of logistic regression, the impact of other birth characteristics such as birth length, birth order (first vs. second born), and prematurity was tested. None of the variables reached statistical significance. Subdividing the twin pairs into those discordant for clinically overt Graves' disease, Hashimoto's thyroiditis, and nonautoimmune thyroid disease did not change the results. This is the first study of the effect of birth weight and other birth characteristics on the subsequent development of clinically overt thyroid disease in which maternal, socioeconomic, and to a high degree, genetic factors have been controlled for. Our study did not show any effect of birth weight or any of the other birth characteristics on the risk of developing clinically overt autoimmune or nonautoimmune thyroid disease.


The impact of parental drinking on children's use of health care.
While a significant body of literature documents the health problems of children caused by and/or associated with parental alcohol misuse, little research has been conducted on the relationship between parental problem drinking and children's use of health care. We should expect to see an increase in children's health care if alcohol-misusing parents were responsive to their children's higher physical and mental health needs. Contrarily, it would decrease (conditional on health status) if alcohol-misusing parents were irresponsive to those needs. Analyzing a nationally representative sample of parents and children, we find a positive and significant association between parental high intensity drinking and pediatric visits for their children.We also find evidence linking parental drinking to more emergency room use. These findings suggest that the impact of parental drinking on child wellbeing should be considered when assessing the full costs of alcohol misuse.


[Psychiatric examination of accused for the "United Nations International Tribunal for the prosecution of persons responsible for serious violations of International Humanitarian Law committed in the territory of the former Yugoslavia" (ICTY)].
Psychiatric examination of accused for the International Tribunal is a new and challenging task for expert medical witness and forensic psychiatry. After a brief description of a case report relevant aspects of psychiatric evaluation of persons responsible for war crimes are outlined and possible implications for forensic research are discussed.


A new preprocessing parameter estimation based on geodesic active contour model for automatic vestibular neuritis diagnosis.
The diagnostic of the vestibular neuritis (VN) presents many difficulties to traditional assessment methods This paper deals with a fully automatic VN diagnostic system based on nystagmus parameter estimation using a pupil detection algorithm. A geodesic active contour model is implemented to find an accurate segmentation region of the pupil. Hence, the novelty of the proposed algorithm is to speed up the standard segmentation by using a specific mask located on the region of interest. This allows a drastically computing time reduction and a great performance and accuracy of the obtained results. After using this fast segmentation algorithm, the obtained estimated parameters are represented in temporal and frequency settings. A useful principal component analysis (PCA) selection procedure is then applied to obtain a reduced number of estimated parameters which are used to train a multi neural network (MNN). Experimental results on 90 eye movement videos show the effectiveness and the accuracy of the proposed estimation algorithm versus previous work.


Painful thumb carpometacarpal joint osteoarthritis: Results of a novel treatment approach.
Pain reduction as well as preservation and improvement in range of motion remain the main aims in the treatment of thumb carpometacarpal (CMC) osteoarthritis (OA). We performed a retrospective outcome analysis of patients with symptomatic stage II-III thumb CMC joint arthritis treated with denervation, joint lavage and capsular imbrication. 73 patients with stage II to III OA of the thumb CMC-joint underwent the described technique. A total of 42 patients complied with follow-up assessment and were included in this study. Mean follow-up was 41.2 (range 12-81) months. Mean operative time was 28.4 (±6.5) minutes. The follow-up assessments showed a significant decrease in pain (preoperative Numerical Rating Scale (NRS): 7.5 - postoperative NRS: 1.1) (p < 0.0001) and a significant improvement in function of the thumb (preoperative DASH-Score: 46.8; Cooney-Wrist-Score: 35.4; Krimmer-Wrist-Score: 38.3 - postoperative DASH-Score: 18.1; Cooney-Wrist-Score: 73.7; Krimmer-Wrist-Score: 80.0) (p < 0.0001). The findings of our study indicate that the presented treatment approach could be a good alternative to more invasive surgical options in patients with stage II-III CMC OA of the thumb, without impairing more invasive surgical options like trapeziectomy or arthroplasty for the future.


Endevouridae, a review with description of four new species (Crustacea, Amphipoda, Lysianassoidea).
The family Endevouridae is reviewed and four new species from the two genera, Endevoura and Ensayara, are described from Australian and Japanese waters. All species are diagnosed and the type species of Endevoura (End. mirabilis Chilton, 1921) and Ensayara (Ens. ramonella J.L. Barnard, 1964), respectively, are redescribed and illustrated. A key to the 19 known world species of Endevouridae is provided.


[What can machines do?]
With increasing computing and storage capacity, the application of big data and artificial intelligence (AI) is almost inexorably finding its way into medicine. The main areas of application so far have been in radiology and pathology, as well as in other areas such as genome sequencing and psychiatry. By evaluating ever larger amounts of data, patterns are sought that can make physicians' work easier by making a preselection. In addition, efforts are being made to uncover previously unrecognized connections. Large amounts of data are recorded by the patients themselves using so-called wearables. How can this data be used meaningfully? What are the dangers? Efforts are also being made in urology to improve the treatment of urinary tract infections and kidney stones, for example, through the use of networked computer systems. Great progress can be expected in the next few years in the field of big data and AI. An enormous expansion of the areas of application is going to come; as such, we are only at the beginning of the development.


Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy.
In this study we performed a step-wise optimization of biologically active IL-2 for delivery using E. coli Nissle 1917. Engineering of the strain was coupled with an in vitro cell assay to measure the biological activity of microbially produced IL-2 (mi-IL2). Next, we assessed the immune modulatory potential of mi-IL2 using a 3D tumor spheroid model demonstrating a strong effect on immune cell activation. Finally, we evaluated the anticancer properties of the engineered strain in a murine CT26 tumor model. The engineered strain was injected intravenously and selectively colonized tumors. The treatment was well-tolerated, and tumors of treated mice showed a modest reduction in tumor growth rate, as well as significantly elevated levels of IL-2 in the tumor. This work demonstrates a workflow for researchers interested in engineering E. coli Nissle for a new class of microbial therapy against cancer.


Behavior of strip footing rested on undrained clay using consistency limits-based constitutive law.
The behavior of undrained clay was extensively studied by many earlier researchers. A lot of constitutive models were developed to describe the behavior of undrained clay based on its mechanical properties. The aim of this research is to present an innovative constitutive model for undrained clay based on its consistency limits and water content. The main concept of this model is to estimate the mechanical properties of clay using earlier correlations with consistency limits, then implement the estimated mechanical properties in a hyperbolic model and calibrate the hyperbolic parameters to match the failure criteria of the undrained clay. To verify the validity of the developed constitutive model, it was applied on a standard problem which is a strip footing rested on undrained clay layer, the results confirmed the ability of the model to simulate the nonlinear behavior of undrained clay up to ultimate condition. The main advantage of this constitutive model is the ability to capture the reduction of mechanical properties of clay with the increase in its water content, which makes it ideal to study the impact of seepage on shallow foundation.


N-Benzyl-p-toluene sulphonamide allows the recording of trains of intracellular action potentials from nerve-stimulated intact fast-twitch skeletal muscle of the rat.
In skeletal muscle, the intracellular recording of trains of action potentials is difficult owing to the movement of the muscle upon stimulation. A potential tool for the removal of muscle movement is the cross-bridge cycle blocker, N-benzyl-p-toluene sulphonamide (BTS), although the effects of BTS on the passive and active membrane properties of intact muscle fibres are not known. Rat extensor digitorum longus (EDL) muscle was used to show that 50 mum BTS reduced tetanic force to approximately 10% of control force, without markedly altering muscle excitability. Incubation with BTS did not alter intracellular K+ content or Na+-K+ pump activity, but produced minor decreases in intracellular Na+ content (7%), resting 22Na+ influx (14%) and excitation-induced 22Na+ influx (29%). Despite these alterations to Na+ fluxes, BTS did not impair muscle excitability, since membrane conductance, resting membrane potential (RMP), rheobase current and the amplitude, overshoot and maximum rate of depolarization of the action potential were all unaltered. However, BTS did induce a small (8%) decrease in the maximum rate of repolarization of the action potential and an increase in the refractory period. The minor effects of BTS on muscle membrane properties did not compromise the ability of the muscle to propagate action potentials, even during tetanic stimulation. In conclusion, BTS can be used successfully to reduce contractility, allowing the intracellular recording of action potentials during both twitch and tetanic contraction of nerve-stimulated muscle, thus making it an excellent tool for the study of electrophysiology in fast-twitch skeletal muscle.


An integrating averager of microspectrofluorometric signals.
Optical signals are used to measure a variety of cell events; in particular, ratiometric fluorescent dyes offer diverse applications, but bring with them the difficult analytical problem of obtaining optical signals at rapidly alternating wavelengths. An improved method for using a computer to record these optical signals is described, and an example record of a Ca+2 transient given. A second technical problem is that ultraviolet (UV) light is required to excite many fluorescent dyes; many common lenses cannot transmit UV light. This article describes the tests needed to measure and optimize the optical path taken by light through a microscope and provides examples with sample lenses.


Paraganglia of the bladder.
Normal paraganglia containing high amounts of catecholamines are a constant feature of the wall of the bladder in elderly men. The paraganglia in this location might give rise to pheochromocytomas. The importance of the local endocrine effects in the regulation of the muscular tone in the bladder is discussed.


[Linkage disequilibrium analysis of the single nucleotide polymorphisms in the PRKCZ gene].
To search for the disease-associated haplotype in the PRKCZ gene, a susceptibility gene for type 2 diabetes in Han population of North China, by case-control study and linkage disequilibrium (LD) analysis using single nucleotide polymorphisms (SNPs). SNPs located in the PRKCZ gene were chosen from public SNP domain by bioinformatic methods and single base extension (SBE) method was used to genotype the loci in 173 sporadic type 2 diabetes patients and 152 normal individuals to perform case-control study and LD analysis. Haplotype block were constructed in these populations. Several SNPs in the PRKCZ gene were found to be associated with the disease. The SNPs formed different haplotype block pattern in case and control groups. The frequencies of the haplotypes formed by 5 SNPs were statistically different between the two groups. The haplotype formed by 5 SNPs in the PRKCZ gene may be associated with type 2 diabetes in Han population of China, which is confirmed from statistics to be a susceptibility gene for the disease.


Spectroscopic Properties, Conformation and Structure of Difluorothiophosphoryl Isocyanate in the Gaseous and Solid Phase.
Difluorothiophosphoryl isocyanate, F2P(S)NCO was characterized with UV/vis, NMR, IR (gas and Ar-matrix), and Raman (liquid) spectroscopy. Its molecular structure was also established by means of gas electron diffraction (GED) and single crystal X-ray diffraction (XRD) in the gas phase and solid state, respectively. The analysis of the spectroscopic data and molecular structures is complemented by extensive quantum-chemical calculations. Theoretically, the Cs symmetric syn-conformer is predicted to be the most stable conformation. Rotation about the P-N bond requires about 9 kJ mol-1 and the predicted existence of an anti-conformer is dependent on the quantum-chemical method used. This syn-orientation of the isocyanate group is the only one found in the gas phase and contained likewise in the crystal. The overall molecular structure is very similar in gas and solid, despite in the solid state the molecules arrange through intramolecular O⋅⋅⋅F contacts into layers, which are further interconnected by S⋅⋅⋅N, S⋅⋅⋅C and C⋅⋅⋅F contacts. Additionally, the photodecomposition of F2P(S)NCO to form CO, F2P(S)N, and F2PNCO is observed in the solid Ar-matrix.


Interimplant femoral fractures: risk factors, treatment and evolution.
The aim of this study is to determine the risk factors involved in the development of these fractures and analyze the treatments used as well as their influence on the clinical and functional prognosis of patients. We made an observational, retrospective case-control study, with a sample of 38 patients (40 femoral bones) operated in our hospital, who had two femoral ipsilateral implants, proximal and distal. We found 10 cases of interimplant fracture and 28 patients who had not suffered a fracture (2 of them had bilateral implants). We analyzed the influence of different variables, such as age, gender, comorbidities, radiological variables, type of treatments employed, clinical evolution, etc. RESULTS: the female sex was predominant in both groups, 80.7 was the average age. Osteoporosis was statistically significant (P=.007) for the development of these fractures. We did not find statistical significance in the radiological variables. Surgical treatment was the most frequent, and the plate of osteosynthesis the most employed option. We found a death rate of 40% at 4 years. Although all fractures healed, the survivors' ambulation ability was reduced. interimplant fractures are predominant in elderly women. Osteoporosis is a statistically significant risk factor. Despite optimal treatment and fracture healing, functional outcomes were decreased. Specific classification systems and therapeutic algorithms are necessary to improve the management and prognosis of these patients.


An integrated platform for directly widely-targeted quantitative analysis of feces part I: Platform configuration and method validation.
Direct analysis is of great importance to understand the real chemical profile of a given sample, notably biological materials, because either chemical degradation or diverse errors and uncertainties might be resulted from sophisticated protocols. In comparison with biofluids, it is still challenging for direct analysis of solid biological samples using high performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Herein, a new analytical platform was configured by online hyphenating pressurized liquid extraction (PLE), turbulent flow chromatography (TFC), and LC-MS/MS. A facile, but robust PLE module was constructed based on the phenomenon that noticeable back-pressure can be generated during rapid fluid passing through a narrow tube. TFC column that is advantageous at extracting low molecular analytes from rushing fluid was employed to link at the outlet of the PLE module to capture constituents-of-interest. An electronic 6-port/2-position valve was introduced between TFC column and LC-MS/MS to fragment each measurement into extraction and elution phases, whereas LC-MS/MS took the charge of analyte separation and monitoring. As a proof of concept, simultaneous determination of 24 endogenous substances including eighteen steroids, five eicosanoids, and one porphyrin in feces was carried out in this paper. Method validation assays demonstrated the analytical platform to be qualified for directly simultaneous measurement of diverse endogenous analytes in fecal matrices. Application of this integrated platform on homolog-focused profiling of feces is discussed in a companion paper.


Photoisomerization spectrum of urocanic acid in human skin and in vitro: effects of simulated solar and artificial ultraviolet radiation.
Ultraviolet (UV) irradiation of trans-urocanic acid (UCA), a major UV absorbing component of the epidermis, leads to the formation of cis-UCA, which mediates immunosuppressive effects. In this study, the net yield of cis-UCA was measured after the photoisomerization of urocanic acid by narrow UV wavebands (spectral range 295-405 nm), with the irradiation doses related to solar irradiance at sea level. The formation of cis-UCA in Caucasian skin (in vivo), as well as in aqueous solution (in vitro), was determined by HPLC analysis. The same irradiation conditions were met in both components of the study. The in vivo experiments showed high efficiency of cis-UCA formation in the spectral region of 305-341 nm, whereas high efficiency in vitro was found at 305 and 326 nm. At 350 and 363 nm, cis-UCA was formed in vivo, but not in vitro. At longer test wavelengths up to 405 nm, no significant formation of cis-UCA was detectable. The established partition between UVB and UVA at 320 nm is not relevant for the isomerization pattern of UCA. Additional studies revealed substantial cis-UCA formation in human skin by UVA phototherapy lamps. Furthermore, raised levels of 295 nm irradiation doses, a possible effect of stratospheric ozone depletion, were found to increase the cis-UCA yield. Our results demonstrate that the formation of cis-UCA in the skin with common exposures takes place over a broad spectrum range of UVB and UVA, up to at least 363 nm. These findings emphasize the potency of UVA to isomerize UCA, and they may contribute to further elucidation of the effects of phototherapy and sunbathing.


Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters.
Several of the ATP-binding cassette (ABC) transporters confer resistance to anticancer agents and/or antiviral agents when overexpressed in drug-sensitive cells. Recently a MRP1 (ABCC1) tricyclic isoxazole inhibitor, LY475776 was shown to be a glutathione-dependent photoaffinity label of human MRP1 and showed poor labeling of murine mrp1, an ortholog that does not confer anthracycline resistance. In the present study, the specificity of LY475776 was examined for its ability to modulate or photolabel orthologs of MRP1 and several other drug efflux transporters of the ABC transporter family. LY475776 modulated MRP1 and Pgp-mediated resistance (MDR, ABCB1) in, respectively, HeLa-T5 and CEM/VLB(100) cells to both vincristine and doxorubicin. LY475776 photolabeled 170kDa Pgp and was inhibited by the potent Pgp inhibitor LY335979 (Zosuquidar.3HCl). The labeling of the 190kDa MRP1 protein in membranes of HeLa-T5 cells was inhibited by substrates of MRP1 such as leukotriene C(4), vincrisine, and doxorubicin and by the inhibitor, MK571. LY475776 did not photolabel human MRP2 (ABCC2), MRP3 (ABCC3), MRP5 (ABCC5) or breast cancer resistance protein (ABCG2). Because LY475776 photolabels murine mrp1 less well than human MRP1 and binds to a region believed important for anthracycline binding, studies were conducted with monkey and canine MRP1 which also show a reduced ability to confer resistance to anthracyclines. Unlike murine mrp1, both orthologs were photolabeled well by LY475776. These studies indicate that the specificity of LY475776 is fairly limited to Pgp and MRP1 and further studies will help to define the binding regions.


Intramedullary brain stem cyst and trapped IV ventricle after infection with Listeria monocytogenes.
We present the rare case of a girl surviving intrauterine listeria brain stem meningoencephalitis, who subsequently developed hydrocephalus, a trapped IV ventricle and an intramedullary cyst. Such cases have been reported only infrequently, and in earlier cases modern imaging studies were not available. Magnetic resonance imaging has been helpful in our patient to delineate the lesions and plan further treatment.


Ultrastructural features of diffuse malignant mesotheliomas.
The distinction of malignant mesothelioma from tumors metastatic to the serosal membranes can often be made based on the results of histochemical or immunohistochemical studies. However, in some cases, these techniques are inadequate to make a firm diagnosis. In these instances, electron microscopic studies with the observation of a constellation of characteristic ultrastructural findings may permit an unequivocal diagnosis of mesothelioma.


MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells.
Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis. MiR-32 has been shown to be upregulated in CRC. In this study, we identified the potential effects of miR-32 on some important biological properties of CRC cells, and clarified the regulation of PTEN by miR-32. The effect of miR-32 on PTEN expression was assessed in CRC cell lines with miR-32 mimics/inhibitor to increase/decrease miR-32 expression. Furthermore, the roles of miR-32 in regulating CRC cells biological properties were analyzed with miR-32 mimics/inhibitor-transfected cells. The 3'-untranslated region (3'-UTR) of PTEN combined with miR-32 was verified by dual-luciferase reporter assay. Gain-of-function and loss-of-function studies showed that overexpression of miR-32 promoted SW480 cell proliferation, migration, and invasion, reduced apoptosis, and resulted in downregulation of PTEN at a posttranscriptional level. However, miR-32 knock-down inhibited these processes in HCT-116 cells and enhanced the expression of PTEN protein. In addition, we further identified PTEN as the functional downstream target of miR-32 by directly targeting the 3'-UTR of PTEN. Our results demonstrated that miR-32 was involved in tumorigenesis of CRC at least in part by suppression of PTEN.


Assessment of cardiomyopathy in fetuses of women with false positive oral glucose loading test.
To evaluate fetal asymmetric septal hypertrophy in women with a false positive oral glucose loading test (OGL). OGL was applied to 79 pregnant women at gestational age between 24 and 28 weeks. The first study group consisted of patients with a normal OGL. Cases having glucose levels above 130 mg/dL after 50 g OGL but a normal 100g oral glucose tolerance test (OGTT) formed a second group. M-mode echocardiography was then performed. Fetal septal and left ventricular posterior wall (LVPW) thicknesses in Group 1 and Group 2 were compared. Mean septal and LVPW thickness was slightly higher in the second group but there was no statistically significant difference between the two groups. Although statistically not significant, there is some increase in septal and ventricular wall thickness in cases with high OGL but normal OGTT. The study also provides evidence of the absence of prominent septal and ventricular thickening in these cases with minimal glucose intolerance.


In vitro steatosis hepatic cell model to compare the lipid-lowering effects of pomegranate peel polyphenols with several other plant polyphenols as well as its related cholesterol efflux mechanisms.
This study was aimed to compare the relative activities of the purified pomegranate peels polyphenols (PPPs) with some other plant polyphenols including punicalagin, ellagic acid, gallic acid, phlorizin, and epigallocatechin gallate (EGCG) on the lipid metabolism regulation, and the cholesterol efflux mechanisms of PPPs and punicalagin were also investigated. In this paper, a convenient and accurate in vitro HL7702 steatosis hepatic cell model was applied to evaluate the lipid-lowering effects of the tested polyphenols. The results showed that PPPs possessed the strongest lipid-lowering effects. Prevention group (treated with polyphenols when establishing of steatosis model) was more effective than treatment group (treated with polyphenols after establishment of steatosis model). Punicalagin displayed the strongest lipid-lowering effects among all the tested components of pomegranate peel polyphenols. Moreover, PPPs and punicalagin (10, 20, 40 μg/mL) significantly increased the mRNA expression of LXRα (Liver X receptor alpha) and its target genes-ABCA1 (ATP-binding cassette transporter A1) in a dose-dependent manner in HL7702 steatosis hepatic cells. The high mRNA expression of LXRα and ABCA1, next to lovastatin, was observed in cells treated with 40 μg/mL of PPPs. These in vitro findings suggested that PPPs might have great potential in the clinic treatment of hyperlipemia.


Correlation between performance and quantity/variability of leg exploration in a contingency learning task during infancy.
Quantity and quality of motor exploration are proposed to be fundamental for infant motor development. However, it is still not clear what types of motor exploration contribute to learning. To determine whether changes in quantity of leg movement and/or variability of leg acceleration are related to performance in a contingency learning task, twenty 6-8-month-old infants with typical development participated in a contingency learning task. During this task, a robot provided reinforcement when the infant's right leg peak acceleration was above an individualized threshold. The correlation coefficient between the infant's performance and the change in quantity of right leg movement, linear variability, and nonlinear variability of right leg movement acceleration from baseline were calculated. Simple linear regression and multiple linear regression were calculated to explain the contribution of each variable to the performance individually and collectively. We found significant correlation between the performance and the change in quantity of right leg movement (r = 0.86, p < 0.001), linear variability (r = 0.71, p < 0.001), and nonlinear variability (r = 0.62, p = 0.004) of right leg movement acceleration, respectively. However, multiple linear regression showed that only quantity and linear variability of leg movements were significant predicting factors for the performance ratio (p < 0.001, adjusted R2 = 0.94). These results indicated that the quantity of exploration and variable exploratory strategies could be critical for the motor learning process during infancy.


Nonsurgical treatment of pelvic rhabdomyosarcoma: a case report.
A 2 1/2-year-old male child with rhabdomyosarcoma of the prostate was treated with radiation of the pelvis, consisting of 5,600 rads in 7 1/2 weeks, and combination chemotherapy of Vincristine and Actinomycin D. Surgery had been refused. The child is alive and disease-free more than 5 years after diagnosis, and over 2 years following the cessation of all therapy. Recent advances in radiotherapy and adjuvant chemotherapy have significantly improved the outlook in this aggressive childhood neoplasm and have made a less aggressive and less mutilating surgical approach often desirable. This, in turn, holds out the prospect of improved quality of survival in children so afflicted.


Lidocaine 20% patch vs lidocaine 5% gel for topical anaesthesia of oral mucosa.
Topical anaesthetics are important to provide pain control at dental injection. The aim was to evaluate the effectiveness of the intraoral topical anaesthetics lidocaine 20% patch (DentiPatch) and lidocaine 5% gel. The randomized unblinded cross-over study included 31 patients (ten boys, 21 girls) aged 13.5 +/- 2.5 years. Application of lidocaine patch or gel was randomly used at first and second visit in the upper premolar region. Heart rate was measured before and at each needle insertion after 2.5, 5, and 15 min and at injection after 15 min. Discomfort and pain were expressed in visual analogue scales (VAS). Paired t-test and Mann-Whitney U-test were used for statistic analyses. Heart rate at buccal injection decreased more when the patch was used (P = 0.0149). Heart rate was lower at the second visit (P = 0.0287). Patients expressed less discomfort when the patch was used on both buccal (P = 0.0150) and palatal (P = 0.0391) site. Boys had lower heart rate and VAS pain scale ratings than girls. Good pain control can reduce the patients' anxiety level--expressed in heart rate--at the second appointment. The patch and gel seem to provide similar pain reduction at needle stick and injection of local anaesthetics.