Histone Deacetylase Inhibitors Sensitize Murine B16F10 Melanoma Cells to Carbon Ion Irradiation by Inducing G1 Phase Arrest.
Epigenetic processes, in addition to genetic abnormalities, play a critical role in refractory malignant diseases and cause the unresponsiveness to various chemotherapeutic regimens and radiotherapy. Herein we demonstrate that histone deacetylase inhibitors (HDACis) can be used to sensitize malignant melanoma B16F10 cells to carbon ion irradiation. The cells were first treated with HDACis (romidepsin [FK228, depsipeptide], trichostatin A [TSA], valproic acid [VPA], and suberanilohydroxamic acid [SAHA, vorinostat]) and were then exposed to two types of radiation (carbon ions and gamma-rays). We found that HDACis enhanced the radiation-induced apoptosis and suppression of clonogenicity that was induced by irradiation, having a greater effect with carbon ion irradiation than with gamma-rays. Carbon ion irradiation and the HDACi treatment induced G2/M and G0/G1 cell cycle arrest, respectively. Thus, it is considered that HDACi treatment enhanced the killing effects of carbon ion irradiation against melanoma cells by inducing the arrest of G1 phase cells, which are sensitive to radiation due to a lack of DNA homologous recombination repair. Based on these findings, we propose that pretreatment with HDACis as radiosensitizers to induce G1 arrest combined with carbon ion irradiation may have clinical efficacy against refractory cancer.


Extracellular Signal-Regulated Kinase 5 is Required for Low-Concentration H2O2-Induced Angiogenesis of Human Umbilical Vein Endothelial Cells.
Background. The aim of this study was to assess the effects of low concentrations of H2O2 on angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and explore the underlying mechanisms. Methods. HUVECs were cultured and stimulated with different concentrations of H2O2. Flow cytometric analysis was used to select an optimal concentration of H2O2 for the following experiments. Cell proliferation, migration, and tubule formation were evaluated by Cell Counting Kit-8 (CCK-8) assays, scratch wound assays, and Matrigel tubule formation assays, respectively. For gain and loss of function studies, constitutively active MEK5 (CA-MEK5) and ERK5 shRNA lentiviruses were used to activate or knock down extracellular signal-regulated kinase 5 (ERK5). Results. We found that low concentrations of H2O2 promoted HUVECs proliferation, migration, and tubule formation. ERK5 in HUVECs was significantly activated by H2O2. Enhanced ERK5 activity significantly amplified the proangiogenic effects of H2O2; in contrast, ERK5 knock-down abrogated the effects of H2O2. Conclusions. Our results confirmed that low concentrations of H2O2 promoted HUVECs angiogenesis in vitro, and ERK5 is an essential mediator of this process. Therefore, ERK5 may be a potential therapeutic target for promoting angiogenesis and improving graft survival.


Bimodal opioid regulation of cyclic AMP formation: implications for positive and negative coupling of opiate receptors to adenylyl cyclase.
A mu-selective opiate receptor agonist, sufentanil, can either increase or decrease the stimulated formation of cyclic AMP (cAMP) in the myenteric plexus. The direction of the opioid modulation of this second messenger depends on the concentration of opioid used. Low doses of opioid enhance, whereas higher concentrations inhibit, the magnitude of cAMP that is formed in response to electrical stimulation. Opioids exert this dual regulation on only stimulated cAMP formation. Basal levels are not affected. Opioid facilitation and inhibition of stimulated cAMP formation are blocked by naloxone, indicating mediation by opiate receptors. Because all experiments were conducted in the presence of a phosphodiesterase inhibitor, it is highly unlikely that opioid regulation of stimulated cAMP formation is due to changes in the rate of its degradation. Positive and negative coupling of mu-opiate receptors to adenylyl cyclase is the most plausible explanation for the bimodal opioid effects on cAMP content. The marked parallel between the current observations and the previously reported bimodal opioid regulation of evoked enkephalin release is consistent with the hypothesis that adenylyl cyclase is one biochemical substrate for the bimodal opiate receptor-coupled regulatory mechanism governing the stimulated release of this opioid peptide.


[Akt involved in diazoxide preconditioning against rat hippocampal neuronal apoptosis induced by anoxia-reoxygenation injury].
Investigate whether preconditioning with diazoxide (DZ), a mitochondrial ATP-sensitive potassium channel opener, could enhance Akt protein to up-regulate Bcl-2/Bax protein ratio against apoptosis. Cultured for 9 - 10 d in vitro, the hippocampal neurons of Sprague-Dawley rats were assigned to the following 5 groups randomly: Control (Group A), Anoxia (Group B), Anoxia + DZ100 micromol/L (Group C), Anoxia + DZ100 micromol/L + 5-hydroxydecanoate (Group D), Anoxia + DZ100 micromol/L + LY294002 50 micromol/L (Group E). Prior to oxygen deprivation, the hippocampal neurons were treated with DZ for 1 h per day and this treatment was persisted for 3 d. Each experiment was repeated for three times and each group contained 16 wells or 2 dishes of neurons for each time. Thereafter, neurons were derived of oxygen for 4 h. At 48 h of reoxygenation the neuronal optical density (A) were measured by MTT method, while the apoptotic rates were assayed by annexin V-FITC staining. The expressions of Akt, Bcl-2 and Bax proteins were detected and evaluated by Western blot. Compared with other pretreatment, DZ 100 micromol/L led to the elevation of A, whereas promoted the decrease of apoptotic rate (P < 0.05). Compared with those in other anoxic groups, the expressions of Akt protein and Bcl-2 protein in Group C were increased significantly (P < 0.05), whereas the Bax density were reduced significantly (P < 0.05). Preceding administration of 100 micromol/L DZ took protective effects on the neurons induced by anoxia-reoxygenation. DZ 100 micromol/L increased Akt protein to up-regulate Bcl-2/Bax protein ratio against apoptosis induced by anoxia-reoxygenation.


A Multi-institutional Analysis of Insurance Status as a Predictor of Morbidity Following Breast Reconstruction.
Although recent literature suggests that patients with Medicaid and Medicare are more likely than those with private insurance to experience complications following a variety of procedures, there has been limited evaluation of insurance-based disparities in reconstructive surgery outcomes. Using a large, multi-institutional database, we sought to evaluate the potential impact of insurance status on complications following breast reconstruction. We identified all breast reconstructive cases in the 2008 to 2011 Tracking Operations and Outcomes for Plastic Surgeons clinical registry. Propensity scores were calculated for each case, and insurance cohorts were matched with regard to demographic and clinical characteristics. Outcomes of interest included 15 medical and 13 surgical complications. Propensity-score matching yielded 493 matched patients for evaluation of Medicaid and 670 matched patients for evaluation of Medicare. Overall complication rates did not significantly differ between patients with Medicaid or Medicare and those with private insurance (P = 0.167 and P = 0.861, respectively). Risk-adjusted multivariate regressions corroborated this finding, demonstrating that Medicaid and Medicare insurance status does not independently predict surgical site infection, seroma, hematoma, explantation, or wound dehiscence (all P > 0.05). Medicaid insurance status significantly predicted flap failure (odds ratio = 3.315, P = 0.027). This study is the first to investigate the differential effects of payer status on outcomes following breast reconstruction. Our results suggest that Medicaid and Medicare insurance status does not independently predict increased overall complication rates following breast reconstruction. This finding underscores the commitment of the plastic surgery community to providing consistent care for patients, irrespective of insurance status.


Antifungal susceptibility and molecular typing of 115 Candida albicans isolates obtained from vulvovaginal candidiasis patients in 3 Shanghai maternity hospitals.
In our multicenter study, we studied the distribution of Candida species in vulvovaginal candidiasis patients and investigated antifungal susceptibility profile and genotype of Candida albicans in vaginal swab. A total of 115 Candida albicans strains were detected in 135 clinical isolates. Minimum inhibitory concentration determinations showed that 83% and 81% of the 115 Candida albicans strains were susceptible to fluconazole and voriconazole. Randomly amplified polymorphic DNA analysis (RAPD) was applied to identify clonally related isolates from different patients at the local level. All tested strains were classified into genotype A (77.4%), genotype B (18.3%), and genotype C (4.3%). Genotype A was further classified into five subtypes and genotype B into two subtypes.Candida albicans was the dominant pathogen of vulvovaginal candidiasis, the majority belonging to genotype A in this study. Exposure to azoles is a risk factor for the emergence of azole resistance among Candida albicans isolated from VVC patients.


An ecological momentary assessment investigation of complex and conflicting emotions in youth with borderline personality disorder.
Non-suicidal self-injury (NSSI) is a prevalent behaviour among people with borderline personality disorder (BPD) but many aspects of the emotional changes that trigger and maintain this behaviour are unknown. This study examines the relationships between NSSI and the number of negative ('negative complex') and opposing valence ('conflicting') emotions. One hundred and seven youth (aged 15-25 years) with first-presentation BPD were assessed using a combination of self-report and ecological momentary assessment to investigate trait levels of emotional acceptance and in vivo changes in the number of negative complex and conflicting emotions before and after self-injurious thoughts and behaviours. Multilevel modelling revealed that changes in the number of negative complex emotions mirrored distress levels before and after self-injurious thoughts and behaviours, approximating a quadratic curve. Increases in the number of negative complex emotions reported prior to self-injurious thoughts and behaviours were associated with lower acceptance of negative emotions. These findings indicate that the number of negative emotions experienced contributes to distress prior to engagement in NSSI. The relationship between non-acceptance of negative emotions and negative complex emotions prior to NSSI suggests that improved emotional awareness and acceptance should be a focus for early interventions aimed at reducing self-injury.


Morphologic diagnosis in neuronal ceroid lipofuscinosis.
Morphologic pathology in NCL is marked by two processes, the interaction of which has not yet been completely clarified: 1) degeneration of nerve cells, foremost in the cerebral cortex, resulting in considerable cerebral atrophy in early childhood forms, likely responsible for clinical and neuroradiological findings; 2) widespread accumulation of autofluorescent lysosomal lipopigments of varying ultrastructure, the demonstration of which is still largely responsible for diagnostic recognition of an individual patient's NCL. Numerous tissues and organs are available for biopsy, among them brain (historical), rectum (still favoured by some), skeletal muscle and peripheral nerves (largely by coincidence or "mistake"), skin and conjunctiva (the latter inferior to former in diagnostic yield) and, most easily retrievable, circulating lymphocytes. The distinct ultrastructure in the circulating lymphocytes permits a close cliniconeuropathological correlation which may only be surpassed by future genetic results. Diagnostic morphology of NCL variants and adult NCL, however, is still problematic, the former concerning autopsy studies of the brain, the latter concerning extracerebral biopsies.


Oxygen therapeutics: oxygen delivery without blood.
Nearly 14 million units of packed red blood cells are transfused in the United States each year. According to the U.S. Department of Health and Human Services, in 1999, 6% of hospitals reported a shortage of blood, resulting in the cancellation or postponement of surgical procedures. The many limitations and risks of transfusions of packed red blood cells in critically ill patients have facilitated interest in developing alternative agents for oxygen delivery. Over the past few decades, safe and effective substitutes have been in development. However, no currently approved agent provides both oxygen transport and volume in place of packed red blood cells. Oxygen therapeutic products have several advantages compared with packed red blood cells, including a prolonged shelf-life, lack of a cross-matching requirement, and minimal infectious risks or concerns about immunogenicity. Hemoglobin-based oxygen carriers and perfluorocarbons are being developed. Two products are undergoing clinical trials. Polyheme is undergoing a phase III study in trauma patients, and Hemopure is being evaluated in a phase II study in patients undergoing cardiopulmonary bypass surgery. A third product (Hemolink) was being evaluated in a phase III study in patients undergoing coronary artery bypass grafting surgery; however, the trial was suspended. In addition, several other hemoglobin-based oxygen carriers are in the preclinical stages. Oxygen therapeutics have several potential clinical applications in the management of perioperative blood loss, trauma, acute normovolemic hemodilution, traumatic brain injury, and blood requirements in patients who refuse or have contraindications to transfusions of red blood cells.


Clinical correlations of motor and somatosensory evoked potentials in neuromyelitis optica.
Motor and somatosensory evoked potentials (MEPs and SSEPs) are sensitive tools for detecting subclinical lesions, assessing disease severity, and determining the prognosis for outcomes of patients with inflammatory neurological diseases such as multiple sclerosis. However, their roles in neuromyelitis optica (NMO), a severe inflammatory neurological disease that predominantly involves optic nerves and spinal cord, have not yet been clarified. Clinical symptoms and examination findings at relapses of 30 NMO patients were retrospectively reviewed. Abnormal MEPs were observed in 69.2% of patients. Patients with abnormal motor central conduction time (CCT) of the lower limbs had higher Kurtzke Expanded Disability Status Scale (EDSS) scores than those with normal responses (P = 0.027). Abnormal SSEPs were found in 69.0% of patients. Patients with abnormal lower limb sensory CCT had higher EDSS scores than those with normal responses (P = 0.019). In 28 patients followed up more than 6 months, only one of 11 patients (9.1%) with normal SSEPs of the lower limbs had new relapses within 6 months, whereas 8 of 17 patients (47.1%, P = 0.049) with abnormal SSEPs of the lower limbs had new relapses. These results indicate MEPs and SSEPs of the lower limbs are good indicators for the disability status at relapses of NMO. Lower limb SSEPs may be a good tool for reflecting the frequency of relapses of NMO.


Diagnostic Clinical Trials in Breast Cancer Brain Metastases: Barriers and Innovations.
Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is vital for early detection and effective treatment. In this study we explored the advances in trial for the diagnosis of BCBM, with review of the literature. On May 8, 2019, we searched ClinicalTrials.gov for interventional and diagnostic clinical trials involving BCBM, without limiting for date or location. Information on trial characteristics, experimental interventions, results, and publications were collected and analyzed. In addition, a systematic review of the literature was conducted to explore published studies related to BCBM diagnosis. Only 9 diagnostic trials explored BCBM. Of these, 1 trial was withdrawn because of low accrual numbers. Three trials were completed; however, none had published results. Modalities in trial for BCBM diagnosis entailed magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, nanobodies, and circulating tumor cells (CTCs), along with a collection of novel tracers and imaging biomarkers. MRI continues to be the diagnostic modality of choice, whereas CT is best suited for acute settings. Advances in PET and PET-CT allow the collection of metabolic and functional information related to BCBM. CTC characterization can help reflect on the molecular foundations of BCBM, whereas cell-free DNA offers new genetic material for further exploration in trials. The integration of machine learning in BCBM diagnosis seems inevitable as we continue to aim for rapid and accurate detection and better patient outcomes.


Detection of Circulating Tumor Cells Using Microfluidics.
Metastasis is the main cause of death in cancer patients worldwide. During metastasis, cancer cells detach from the primary tumor and invade distant tissue. The cells that undergo this process are called circulating tumor cells (CTCs). Studies show that the number of CTCs in the peripheral blood can predict progression-free survival and overall survival and can be informative concerning the efficacy of treatment. Research is now concentrated on developing devices that can detect CTCs in the blood of cancer patients with improved sensitivity and specificity that can lead to improved clinical evaluation. This review focuses on devices that detect and capture CTCs using different cell properties (surface markers, size, deformability, electrical properties, etc.). We also discuss the process of tumor cell dissemination, the biology of CTCs, epithelial-mesenchymal transition (EMT), and several challenges and clinical applications of CTC detection.


Clinical characteristics of familial generalized anxiety disorder.
The authors seek to determine whether the clinical characteristics of generalized anxiety disorder (GAD) differ in individuals with a high vs. low familial vulnerability to illness. We identified 486 personally interviewed female twins from a population-based register who had both an interviewed co-twin and a lifetime history of GAD using modified DSM-III-R criteria which required a one-month minimum duration of illness. We attempted to predict risk for GAD in the co-twin from the clinical features of the GAD in the proband twin using the Cox proportional hazard model, controlling for year of birth and zygosity. Only two variables uniquely predicted an increased risk for GAD in the co-twin: number of GAD symptoms endorsed and comorbidity with bulimia. Variables that did not uniquely predict risk of illness in the co-twin included age at onset, duration of the longest episode and number of episodes. The familial vulnerability to GAD can be meaningfully indexed by clinical features of the syndrome. These results suggest that if the syndrome of GAD is to be narrowed, it would, from a familial perspective, be more valid to increase the minimum number of required symptoms rather than to increase the minimum duration of illness.


Development of GFAP-positive cells and reactive changes associated with cystic lesions in HTX rat brain.
HTX rat, a congenital hydrocephalic strain, develops ventricular dilatation and cystic cavities in the cerebral white matter after birth. To investigate the reactive changes in glial cells around these cavities, immunohistochemical staining for glial fibrillary acidic protein (GFAP), a specific marker protein of astrocytes, and bromodeoxyuridine (BrdU), a thymidine analogue, was carried out on 107 Wistar and HTX rat brains from birth to postnatal day (P) 26. Animals were divided into three groups: Group A, Wistar rats as normal controls; Group B, HTX rats with a normal structure or only mild ventricular dilatation without any lesion in the white matter; and Group C, HTX rats with severe ventricular dilatation and cyst formation in the white matter. Group B rats showed similar development of GFAP-positive (GFAP+) cells to that in Group A rats, both morphologically and quantitatively. On the other hand, Group C rats showed definite structural changes in GFAP+ cells around the cystic cavities from P5. These included enriched cytoplasm and thickened cell processes with increased GFAP expression, and enveloped most cyst walls from P10. However, quantitative examination of the percentage of GFAP+ cells in Group C rats showed a similar developmental profile to those in Group A and B rats. Furthermore, the labeling index of BrdU-positive cells, indicating S-phase cells, in the white matter in Group C rats showed a similar decreasing pattern to that in Group A and B rats from P1 to P26.(ABSTRACT TRUNCATED AT 250 WORDS)


Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study.
Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients.


Congenital Hypothyroidism Long-Term Follow-up Project: Navigating the Rough Waters of a Multi-Center, Multi-State Public Health Project.
The Region 4 Midwest Genetics Collaborative, made up of seven regional states (Illinois, Indiana, Kentucky, Michigan, Minnesota, Ohio, and Wisconsin), brought together pediatric endocrinologists, state laboratory experts, public health follow-up specialists, and parents of children with congenital hypothyroidism (CH) to identify the three-year follow-up management and education patterns of primary care clinicians and pediatric endocrinologists in the care of children diagnosed with CH by state newborn screening (NBS) programs. Among a number of challenges, each state had different NBS methods, data systems, public health laws, and institutional review board (IRB) requirements. Furthermore, the diagnosis of CH was complicated by the timing of the NBS sample, the gestational age, weight, and co-morbidities at delivery. There were 409 children with CH identified through NBS in 2007 in the seven state region. The clinician of record and the parents of these children were invited to participate in a voluntary survey. Approximately 64 % of clinician surveys were collected with responses to questions relating to treatment, monitoring practices, educational resources, genetic counseling, and services provided to children with confirmed CH and their families. Nearly one-quarter (24 %) of parents surveyed responded to questions relating to treatment, education, genetic counseling, resources, and services they received or would like to receive. De-identified data from six of the seven states were compiled for analysis, with one state being unable to obtain IRB approval within the study timeline. The data from this collaborative effort will improve state follow-up programs and aid in developing three-year follow-up guidelines for children diagnosed with CH. To aid in the facilitation of similar public health studies, this manuscript highlights the challenges faced, and focuses on the pathway to a successful multi-state public health endeavor.


Effects of estrogen on the turnover rates of ornithine amino transferase in rat liver and kidney.
The turnover rates of ornithine aminotransferase in the liver and kidney of control rats and those treated with estrogen were determined by injecting L-[14C]leucine (U) and following the decay of specific radioactivity incorporated into immunoprecipitates from the partially purified enzymes. The half-life of the ornithine aminotransferase [EC 18.104.22.168] in the liver (t1/2=0.95 days) was significantly different from that of the kidney enzyme (t1/2=4.0 days). Studies on the incorporation of radioactive leucine into ornithine aminotransferase in the kidney under steady-state conditions showed that the rate of synthesis of this enzyme after treatment with estrogen was 5 to 6 times higher than that in untreated animals. The rate constant of degradation of kidney ornithine aminotransferase under steady-state conditions induced by estrogen treatment was not significantly different from that under control conditions. The results showed that the increase in the rate of biosynthesis, not to a decrease in the rate of degradation. No significant changes in the rates of biosynthesis and degradation of liver ornithine aminotransferase were observed after administration of estrogen.


Short-term Effects of Static Stretching on Hamstring Passive Stiffness in Young and Older Women.
The objectives of this study were to assess the acute effects of static stretching on hamstring passive stiffness in young and older women. A secondary objective was to compare hamstring muscle size and quality measurements (cross-sectional area and echo intensity) between the two groups and to determine if these characteristics are related to passive stiffness at baseline. Fifteen young (23±4 years) and 15 older (73±5 years) women underwent two randomized conditions that included a control treatment and an experimental treatment of four, 15-s static stretches of the hamstrings. Passive stiffness was calculated before (pre-test) and after (post-test) each treatment using a passive knee extension test. Ultrasound imaging was used to measure hamstring muscle cross-sectional area and echo intensity. Passive stiffness collapsed across group decreased from pre- to post-test for the stretching treatment (P=0.001) but not for the control (P=0.467). The older women had lower cross-sectional area (P=0.033) and greater baseline (pre-test) passive stiffness (P=0.042-0.049) and echo intensity (P=0.022) than the young women. Moreover, baseline passive stiffness was significantly related to echo intensity (r=0.430, P=0.018) but not cross-sectional area (r=-0.014, P=0.943). An acute bout of static stretching decreased passive stiffness in both young and older women.


[Should the presence of Mycobacterium tuberculosis be demonstrated before the treatment of patients with suspected pulmonary tuberculosis?].
In Denmark, treatment of tuberculosis is generally only recommended if the diagnosis is confirmed bacteriologically, which may cause a delay in treatment. We investigated the duration of the treatment delay, and if the delay would cause any serious health problems for the individual or risk of contact infections by a retrospective examination of 324 cases of pulmonary tuberculosis. The mean treatment delay was longer in older age groups. Regarding death due to delay, we found no risk for the patients who are not weakened by old age or another disease. Only 11 (3.6%) above the age of ten years were treated without bacteriological confirmation (1% for Danes). The infection risk from the smear negative, but culture positive patients was minimal, as only one subject was definitely infected from a smear negative subject. In conclusion, we find the epidemiologic and individual risk sufficiently low to continue our rather restrictive treatment policy.


Comparative diagnostic accuracy of magnetic resonance imaging and immunoscintigraphy for detection of bone marrow involvement in patients with malignant lymphoma.
To compare the diagnostic accuracy of magnetic resonance imaging (MRI) and immunoscintigraphy (IS) for detection of bone marrow infiltration in malignant lymphoma. In 32 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), MRI of the axial skeleton and whole-body IS using technetium-99m (99mTc)-labeled monoclonal antibodies were reviewed and compared with iliac crest biopsies. Criterion for marrow infiltration was a positive biopsy or concordant positive results of MRI and IS. In 16 patients (50%), MRI, IS, and iliac crest biopsies were negative for marrow infiltration. Iliac crest biopsy showed infiltration in only four patients (13%). Infiltration was missed in two of 32 patients with IS and in one patient with MRI. In one additional patient, MRI was false-positive because of pelvic hematopoietic hyperplasia. A subset of nine patients (28%) with negative biopsies had bone marrow involvement according to MRI and IS with identical location and pattern of infiltration. In eight of these nine patients, diagnostic imaging indicated marrow involvement only in noncrest marrow. Subsequent biopsy confirmed infiltration in five patients. The clinical course suggested true-positive imaging results in the remaining four patients. Two patients (6%) remained equivocal. Overall concordance of MRI and IS for marrow infiltration was 88% (28 of 32 patients). Diagnostic imaging is essential for optimal staging in malignant lymphoma, as blind biopsies appear to have low sensitivity for bone marrow infiltration because of frequent involvement in noncrest marrow. both imaging modalities show a high rate of detection of bone marrow infiltration.


Fatty acid requirement of Treponema denticola and Treponema vincentii.
Treponema denticola and Treponema vincentii were cultured in a medium supplemented with either 0.2 or 0.4% (w/v) alpha globulin in place of serum. The active factor(s) in alpha globulin was stable at pH 7.0 to autoclaving and was nondialyzable. Extraction of lipids from alpha globulin showed that both protein and lipid, supplied by the alpha globulin, were required for maximal growth of these two oral treponemes. The lipid component was investigated by adding sodium salts of long-chain fatty acids to the basal medium supplemented with 0.4% delipified alpha globulin. The lipid component of alpha globulin was replaced by either oleic acid (cis-18:1(9)) or by elaidic acid (trans- 18:1 (9)0. No other saturated or unsaturated fatty acid tested could support good growth. Tween 80 (polysorbitan monooleate) was the only Tween compound able to support maximal growth of T. denticola. The cellular lipids of T. denticola, grown with oleate in broth supplemented with 0.4% delipified alpha globulin, were extracted and analyzed by gas chromatography. The principle fatty acids were myristic, pentadecanoic, and palmitic acids. Lesser amounts of oleic acid, eicosadienoic acid, and an unidentified fatty acid (retention time, 88 min) were also detected. Treponema denticola appears to be capable of limited synthesis of cellular fatty acids such as myristic, pentadecanoic, and palmitic acids from oleic acid.


[Tetanus in cats: 3 case descriptions].
Three cats with spasticity on one leg or on all four limbs were presented between 1996 and 1998 at the Department of clinical veterinary medicine, Section of neurology, Vetsuisse-Faculty of Bern. The presumptive diagnosis was tetanus. A focal form was present in two cases and generalised tetanus in one cat. All cats had a history of injury at the affected legs respectively at the neck. The first clinical signs were seen between two days and three weeks after injury. The bacteriologic examination of serous fluid from the site of injury revealed an infection with Clostridium. EMG in one cat during anaesthesia showed motor united potentials (MUPs) on the spastic leg. All patients received antibiotics (Penicillin, respectively Amoxicillin/Clavulanic acid and Metronidazol). Supportive aid were initially sedation, wound revision and in one cat nutrition through oesophageal sonde. In a second phase physiotherapy was performed. All three animals were significantly better after a couple of weeks, two cats were without symptoms after eight and five weeks respectively.


Paroxysmal nocturnal hemoglobinuria superimposed with preeclampsia.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by complement-mediated intravascular hemolysis. As maternal complication of PNH is already severe, it becomes much more complex when preeclampsia is superimposed. We present a case of PNH superimposed with severe preeclampsia in the third trimester. A 30-year-old, gravida 1, para 0, woman had PNH, diagnosed at the age of 17. Her PNH was stable under medication. In 2004, she conceived and had prenatal care at our hospital. At 35 weeks of gestation, preeclampsia with elevated blood pressure and proteinuria were superimposed and managed with close surveillance. A live male baby was delivered vaginally at 38 weeks of gestation. During parturition, her blood pressure increased to 180/100 mmHg. Thrombocytopenia, hyponatremia, hyperkalemia, hypoalbuminemia, elevated liver enzymes and lactate dehydrogenase were also noted. Preeclampsia continued to postpartum and eventually disappeared. The most frequent causes of PNH-related fetomaternal morbidity and mortality are hemolysis and thrombosis. The situation becomes even more complicated when PNH is superimposed with preeclampsia. Appropriate clinical surveillance, awareness of the potential risks of hemolysis and thrombosis, as well as evaluation of fetal wellbeing are essential.


Multimode optical waveguide enabling microbends with low inter-mode crosstalk for mode-multiplexed optical interconnects.
A vertical multimode waveguide enabling micro-bends is proposed for mode-multiplexed optical interconnect links. The multimode waveguide is designed to be singlemode in the lateral direction and support higher-order modes in the vertical direction. The characteristic analysis for an SOI (silicon-on-insulator)-based vertical multimode waveguide with a ~0.3μm × ~1.5μm cross section is given as an example. The theoretical pure bending loss is negligible for all the lowest eight modes when the bending radius is even less than 5μm. When light goes through the structure consisting of a straight section connected with a bent section, it is found that some inter-mode crosstalk is caused by the significant mode hybridization happening in the sharply bent multimode waveguide. For the designed SOI-based vertical multimode waveguide, the inter-mode crosstalk is lower than -20dB even when the bending radius is chosen as small as R = 10μm, which is one order smaller than that for the traditional lateral multimode waveguide (whose minimal bending radius is about 130μm). The inter-mode crosstalk can be even reduced to -30dB when choosing R = 30μm. Such a multimode optical waveguide microbend with low inter-mode crosstalk is promising for realizing compact mode-multiplexing links.


Particle-Hole Duality in the Lowest Landau Level.
We derive a number of exact relations between response functions of holomorphic, chiral fractional quantum Hall states and their particle-hole (PH) conjugates. These exact relations allow one to calculate the Hall conductivity, Hall viscosity, various Berry phases, and the static structure factor of PH conjugate states from the corresponding properties of the original states. These relations establish a precise duality between chiral quantum Hall states and their PH conjugates. The key ingredient in the proof of the relations is a generalization of Girvin's construction of PH-conjugate states to inhomogeneous magnetic field and curvature. Finally, we make several nontrivial checks of the relations, including for the Jain states and their PH conjugates.


Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis.
Paeoniflorin is an active ingredient derived from Paeonia, which has an anti-inflammatory effect. However, the potential role and basis of paeoniflorin in rheumatoid arthritis (RA) are indistinct. Cell viability, cycle distribution, migration, and invasion were evaluated via Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. The contents of inflammatory cytokines were examined using enzyme-linked immunosorbent assay (ELISA). RNA expression levels were determined via qRT-PCR and western blot. The targeting relationship between miR-671-5p and circ-FAM120A (hsa_circ_0003972) or murine double minute 4 (MDM4) was validated via dual-luciferase reporter assay. Paeoniflorin restrained proliferation, migration, invasion, and inflammation and accelerated cell cycle arrest in RA fibroblast-like synoviocytes (RA-FLSs). Circ-FAM120A was boosted in RA synovial tissues and RA-FLSs. Circ-FAM120A upregulation, miR-671-5p knockdown, or MDM4 augmentation reversed the repressive effect of paeoniflorin on RA-FLS progression. Moreover, paeoniflorin attenuated RA-FLS progression by regulating the circ-FAM120A/miR-671-5p/MDM4 axis. Paeoniflorin inhibited RA-FLS proliferation, mobility, and inflammation and triggered cell cycle arrest via mediating the circ-FAM120A/miR-671-5p/MDM4 pathway.


[Preparation and in vivo evaluation of pH and time dependent Yuchangning tablets for colon-specific delivery].
Taking Chinese compound medicine Yuchangning as a research model, prepared the pH and time dependent Yuchangning tablets for colon-specific delivery (PT-YT-CSD), and evaluated the releasing property in vitro. The coating prescription is filtered by the release extent of matrine and oxymatrine in vitro and the wicking rate of the tablet, which including the category and proportion of film forming agent and porogen, the sort and dosage of fluidizing agent, the increment of weight after coating and so on. The releasing property of the preparation is evaluated by the dissolution tests in vitro through measuring the content of matrine and oxymatrine content. The preparation method of the PYTCSD: After prepared plain tablets, the 95% alcoholic solution of EC and Eudragit II are mixed in a 7:3 EC: Eudragit II ratio and then added in DEP up to 10% of the coating amount, reduced the alcohol concentration to 4% by diluting with ethonal. Tablet was coated by the alcohol solution and the weight of the plain tablet was increased by 3%. The dissolution tests in vitro indicated that matrine and oxymatrine were not dissolved in the simulated gastric juice after 2 h. The accumulative quantities of matrine and oxymatrine were less than 10% in the simulated intestinal juice after 4 h. The quantities of matrine and oxymatrine are 75.7% and 76.8% in the simulated colon juice after 1 h. The PYTCSD was prepared and the preparation could fulfil the aim of delivering in the specific colon in vitro.


TAT-mediated transcellular activation of HIV-1 long terminal repeat directed gene expression by HIV-1-infected peripheral blood mononuclear cells.
We have previously shown evidence of Tat-mediated transcellular activation of the HIV-1 long terminal repeat (LTR) in vitro by using a laboratory-adapted strain of HIV-1. To examine the biologic significance of this observation, we asked whether primary PBMCs from HIV-1-infected individuals will transactivate the HIV-1 LTR transcellularly in suitable indicator cells. In cultures of PBMCs isolated from HIV-1-infected patients at various clinical stages, with either HIV-1 LTR-transfected Jurkat T cells or nonfusigenic HIV-1 LTR-transfected murine fibroblasts, transcellular activation was readily detected. Transactivation of the LTR in cocultured cells with HIV-1-infected PBMCs is detectable 1 to 2 wk before the onset of significant virus production and at ratios as low as 1 infected cell to 10(6) surrounding cells. Addition of the Tat inhibitor RO5-3335 substantially decreases transcellular activation, even at low concentrations (0.01 microM) that do not affect virus levels. In contrast, addition of the antiretroviral agent zidovudine has no effect on transcellular activation. These data suggest that Tat-mediated transcellular activation of the HIV-1 LTR occurs independently of cellular infection, and provides a mechanism that can promote the spread of HIV-1 in susceptible cell populations.


Effect of nitrogen concentration of the nutrient solution on the volatile constituents of leaves of Salvia fruticosa Mill. in solution culture.
Essential oils from hydroponically cultivated Salvia fruticosa were analyzed by GC-MS techniques. Three different levels of nitrogen (100, 150, and 200 mg/L) were used in the nutrient solution for the cultivation, using the nutrient film technique. A total of 79 compounds were identified, and qualitative and quantitative differences have been observed between the samples collected at full bloom (flowering stage) and at the end of the seed formation stage. 1,8-Cineole, beta-caryophyllene, and viridiflorol were the predominant constituents in most cases. 13-epi-Manool was identified by using GC parameters and mass spectrum fragmentation pattern, whereas labd-7,13-dien-15-ol, a labdane type diterpene, was identified for the first time in the genus Salvia, using GC parameters and an authentic sample. The results obtained from GC-MS analyses were submitted to chemometric analysis.


Spatial Connectivity and Temporal Dynamic Functional Network Connectivity of Musical Emotions Evoked by Dynamically Changing Tempo.
Music tempo is closely connected to listeners' musical emotion and multifunctional neural activities. Music with increasing tempo evokes higher emotional responses and music with decreasing tempo enhances relaxation. However, the neural substrate of emotion evoked by dynamically changing tempo is still unclear. To investigate the spatial connectivity and temporal dynamic functional network connectivity (dFNC) of musical emotion evoked by dynamically changing tempo, we collected dynamic emotional ratings and conducted group independent component analysis (ICA), sliding time window correlations, and k-means clustering to assess the FNC of emotion evoked by music with decreasing tempo (180-65 bpm) and increasing tempo (60-180 bpm). Music with decreasing tempo (with more stable dynamic valences) evoked higher valence than increasing tempo both with stronger independent components (ICs) in the default mode network (DMN) and sensorimotor network (SMN). The dFNC analysis showed that with time-decreasing FNC across the whole brain, emotion evoked by decreasing music was associated with strong spatial connectivity within the DMN and SMN. Meanwhile, it was associated with strong FNC between the DMN-frontoparietal network (FPN) and DMN-cingulate-opercular network (CON). The paired t-test showed that music with a decreasing tempo evokes stronger activation of ICs within DMN and SMN than that with an increasing tempo, which indicated that faster music is more likely to enhance listeners' emotions with multifunctional brain activities even when the tempo is slowing down. With increasing FNC across the whole brain, music with an increasing tempo was associated with strong connectivity within FPN; time-decreasing connectivity was found within CON, SMN, VIS, and between CON and SMN, which explained its unstable valence during the dynamic valence rating. Overall, the FNC can help uncover the spatial and temporal neural substrates of musical emotions evoked by dynamically changing tempi.


Aeromonas species in septicemia: laboratory characteristics and clinical observations.
We retrospectively analyzed clinical and epidemiological data on and laboratory characteristics of 53 cases of aeromonas septicemia. Only four Aeromonas genomospecies (species defined by DNA relatedness) were associated with the 53 cases, with Aeromonas hydrophila (sensu stricto) predominating (47%). Nearly 60% of all Aeromonas isolates from blood fell into one of four somatic groups: serogroups O:11, O:16, O:18, and O:34. Unlike Aeromonas-associated gastroenteritis, septicemia did not peak in frequency during the warmer months but rather was most common in January through March, when approximately 40% of cases occurred. In vitro tests of the pathogenicity of 20 selected blood isolates of Aeromonas indicated that resistance to complement-mediated lysis, elevated levels of protease and hemolysin activity, and the ability to elaborate siderophores correlated with higher virulence. Species and serogroup designations also correlated with the degree of virulence. Susceptibility studies of 50 strains indicated that A. hydrophila was the most drug-resistant species and that Aeromonas veronii was the most susceptible. Susceptibility to first- and second-generation cephalosporins and carbenicillin was species-associated.


Intracranial Efficacy of Systemic Therapy in Patients with Asymptomatic Brain Metastases from Lung Cancer.
There has been controversy over whether to radiologically follow up or use local treatment for asymptomatic small-sized brain metastases from primary lung cancer. For brain tumors without local treatment, we evaluated potential factors related to the brain progression and whether systemic therapy controlled the tumor. We analyzed 96 patients with asymptomatic small-sized metastatic brain tumors from lung cancer. These underwent a radiologic follow-up every 2 or 3 months without local treatment of brain metastases. The pathologies of the tumors were adenocarcinoma (n = 74), squamous cell carcinoma (n = 11), and small cell carcinoma (n = 11). The primary lung cancer was treated with cytotoxic chemotherapy (n = 57) and targeted therapy (n = 39). Patients who received targeted therapy were divided into first generation (n = 23) and second or third generation (n = 16). The progression-free survival (PFS) of brain metastases and the overall survival (OS) of patients were analyzed depending on the age, tumor pathology, number, and location of brain metastases, the extent of other organ metastases, and chemotherapy regimens. The median PFS of brain metastases was 7.4 months (range, 1.1-48.3). Targeted therapy showed statistically significant PFS improvement compared to cytotoxic chemotherapy (p = 0.020). Especially, on univariate and multivariate analyses, the PFS in the second or third generation targeted therapy was more significantly improved compared to cytotoxic chemotherapy (hazard ratio 0.229; 95% confidence interval, 0.082-0.640; p = 0.005). The median OS of patients was 13.7 months (range, 2.0-65.0). Univariate and multivariate analyses revealed that the OS of patients was related to other organ metastases except for the brain (p = 0.010 and 0.020, respectively). Three out of 52 patients with brain recurrence showed leptomeningeal dissemination, while the recurrence patterns of brain metastases were mostly local and/or distant metastases (94.2%). Of the 52 patients who relapsed, 25 patients received local brain treatment. There was brain-related mortality in two patients (2.0%). The intracranial anti-tumor effect was superior to cytotoxic chemotherapy in the treatment of asymptomatic small-sized brain metastases with targeted therapy. Consequently, it becomes possible to determine the optimal timing for local brain treatment while conducting radiological follow-up for these tumors, which do not appear to increase brain-related mortality. Furthermore, this approach has the potential to reduce the number of cases requiring brain local treatment.


A loaf of bread: Price and value.
In the Western world, the basic staple of nutrition is bread. It evolved, from Neolithic times in Mesopotamia and the Levant, from flour made from natural hybrids of emmer and einkorn. Its form has changed from that of a dark, coarse and heavy loaf, baked in the ashes, to the enriched artistic breads of the late twentieth century. Its variety of forms conferred status on those who ate its refined and whitened form. The wheel of fashion and nutrition has turned full circle to the quality-controlled, vitamin and mineral-enriched wholemeal loaf of the new millennium to come. Bread has changed from a staple not simply of nutrition itself, but to that of a 'functional food' whose fibre confers protection against preventible disease. The bread of the new century thus will be both a food and a medicine. So fundamental to Western life is bread, that its price has long been the last item to remain controlled, when all else is left to the dictates of a free market economy. Bread is the fundamental unit of exchange and forms the last link in a chain of commodities which starts from items of luxury to those of survival itself. The price of bread can thus be used as a currency datum. As such, the price of a loaf of bread, and the minutes of labour needed to produce it, can be used to measure the economy, and to give a measured perspective of its influence on a community's history. Costs, throughout history, can be expressed in 'bread units'. As such, the latter forms an absolute index of the worth of other items, particularly a person's labour. As such, bread and its value forms a partly independent measure of inflationary and other social influences. Bread remains a fundamental part not only of nutrition, but of life itself.


Cryosurgery by tetrafluoroethane: An answer to black gums.
To highlight the effect of 1,1,1,2 tetrafluoroethane (TFE), a new material for cryosurgery of gingival melanin pigmentation (GMP). Five patients were treated using a TFE-cooled swab and the pre- and post-treatment photographs were compared. Complete keratinization took place in 3-4 weeks after application without any trace of pigmentation. During the follow-up period, no side effects were observed and the improved esthetics were maintained upto 1 year.


Acute thiamine deficiency in diabetic ketoacidosis: Diagnosis and management.
Persistent encephalopathy in a patient with diabetic ketoacidosis is often feared as a sign of cerebral edema. Although thiamine deficiency is a rare diagnosis in children, marginal nutritional status and osmotic diuresis may be risk factors. The objective was to describe a heretofore unreported cause of encephalopathy in a child with diabetic ketoacidosis and review the mechanisms and pathophysiology of thiamine deficiency in this clinical scenario. Case report and review of the literature. Pediatric intensive care unit of a tertiary care pediatric hospital. A 13-yr-old girl. Treatment of dehydration and hyperglycemia, osmotherapy, and intravenous thiamine administration. The patient presented with new-onset diabetes mellitus, severe diabetic ketoacidosis, and significant encephalopathy. Despite biochemical improvement with treatment of dehydration and hyperglycemia, her encephalopathy persisted. Computed tomography did not show cerebral edema and she showed no response to osmotherapy. Quantitative and functional assays revealed severe thiamine deficiency. The patient showed an immediate and dramatic response to intravenous thiamine administration. The clinical improvement as well as lab investigations suggests that thiamine deficiency was the cause of this child's encephalopathy. Because potential mechanisms exist for thiamine deficiency in diabetes mellitus and institution of insulin and glucose therapy may stress thiamine body stores, thiamine deficiency should be considered in children with diabetic ketoacidosis whose encephalopathy does not improve with improvement of biochemical status.


[Secondary injury to the spine due to static insufficiency in thigh amputees (author's transl)].
On the basis of a study of the literature, our own investigation as well as clarification of the mobility of the pelvis and spine in thigh amputees, it was established that secondary alterations occur in the spine which represent a degeneration in terms of vocational fittness. In spite of numerous publication by various researchers, this recognition has not yet been widely accepted. Reference is made to the significance of the small vertebral joint mechanism. Additional basic research is required here.


Localized tracheobronchial amyloidosis: A rare case presentation and tailored management approaches.
Localized tracheobronchial amyloidosis (TBA) is a rare manifestation of pulmonary amyloid disease, and can result in central airway obstruction. The nature of presentation is variable and there may be a delayed diagnosis. TBA has a variable prognosis and the most commonly used strategy for management is airway recanalization. Here, we describe the tailored management approach for a 64-year-old Caucasian female presenting with localized TBA of the left main bronchus. Pulmonary function testing, computed tomography and positron emission tomography results are detailed. Rigid bronchoscopy was utilized for diagnostic and therapeutic intervention, which involved debulking and stent insertion. Amyloid deposition and localized inflammation were identified through histopathology. Focal external beam radiation therapy was administered following multidisciplinary discussion and review of the literature, with no evidence of active disease at 6 months follow-up.


Preferential solvation within hydrophilic nanocavities and its effect on the folding of cholate foldamers.
The conformations of three cholate foldamers and one molecular basket were studied by fluorescence and NMR spectroscopy. In nonpolar solvents (e.g., hexane/ethyl acetate or ethyl acetate) mixed with a small amount of a polar solvent (e.g., alcohol or DMSO), the cholate oligomer folded into a helix with the hydrophilic faces of the cholates turned inward. Folding created a hydrophilic nanocavity preferentially solvated by the entrapped polar solvent concentrated from the bulk. This microphase separation of the polar solvent was critical to the folding process. Folding was favored by larger-sized polar solvent molecules, as fewer such molecules could occupy and solvate the nanocavity, thus requiring a smaller extent of phase separation during folding. Folding was also favored by smaller/acyclic nonpolar solvent molecules, probably because they could avoid contact with the OH/NH groups within the nanocavity better than larger/cyclic nonpolar solvent molecules.


Quantitative autoradiographic localization of [125I]insulin-like growth factor I, [125I]insulin-like growth factor II, and [125I]insulin receptor binding sites in developing and adult rat brain.
Insulin-like growth factors I and II (IGF I and IGF II) and insulin itself, which are structurally related polypeptides, play an important role in regulating brain growth and development as well as in the maintenance of its normal functions during adulthood. In order to provide a substrate for the better understanding of the roles of these growth factors, we have investigated the anatomical distribution as well as the variation in the density of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites in developing and adult rat brain by in vitro quantitative autoradiography. The distributional profile of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites showed a widespread but selective regional localization throughout the brain at all stages of development. The neuroanatomic regions which exhibited relatively high density of binding sites with each of these radioligands include the olfactory bulb, cortex, hippocampus, choroid plexus, and cerebellum. However, in any given region, receptor binding sites for IGF I, IGF II, or insulin are concentrated in anatomically distinct areas. In the cerebellum, for example, [125I]IGF II receptor binding sites are concentrated in the granular cell layer, [125I]insulin binding sites are localized primarily in the molecular layer, whereas [125I]IGF I receptor binding sites are noted in relatively high amounts in granular as well as molecular cell layers. The apparent density of sites recognized by each radioligand also undergoes remarkable variation in most brain nuclei, being relatively high either during late embryonic (i.e., IGF I and IGF II) or early postnatal (i.e., insulin) stages and then declining gradually to adult levels around the third week of postnatal development. These results, taken together, suggest that each receptor-ligand system is regulated differently during development and thus may have different roles in the process of cellular growth, differentiation, and maintenance of the nervous system. Furthermore, the localization of [125I]IGF I, [125I]IGF II, and [125I]insulin receptor binding sites over a wide variety of physiologically distinct brain regions suggests possible involvement of these growth factors in a variety of functions associated with specific neuronal pathways.


The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and reduction in PARP activity in vivo.
ABT-888 is a potent, orally bioavailable PARP-1/2 inhibitor shown to potentiate DNA damaging agents. The ability to potentiate temozolomide (TMZ) and develop a biological marker for PARP inhibition was evaluated in vivo. Doses/schedules that achieve TMZ potentiation in the B16F10 syngeneic melanoma model were utilized to develop an ELISA to detect a pharmacodynamic marker, ADP ribose polymers (pADPr), after ABT 888 treatment. ABT-888 enhanced TMZ antitumor activity, in a dose-proportional manner with no observed toxicity (44-75% tumor growth inhibition vs. TMZ monotherapy), but did not show single agent activity. Extended ABT-888 dosing schedules showed no advantage compared to simultaneous TMZ administration. Efficacy correlated with plasma/tumor drug concentrations. Intratumor drug levels correlated with a dose-proportional/time-dependent reduction in pADPr. Potentiation of TMZ activity by ABT-888 correlated with drug levels and inhibition of PARP activity in vivo. ABT-888 is in Phase 1 trials using a validated ELISA based on the assay developed here to assess pharmacological effect.


Pain assessment in a children's A&E: a critical analysis.
In this particular children's A&E department it is evident that pain assessment is a high priority among the nursing staff. Pain is routinely assessed on every child during triage, so analgesia is given as soon as possible and children are not left suffering pain for an unnecessary length of time. However, because pain is not routinely reassessed it is often unknown whether the pain has been fully relieved. It appears that not all the resources available for assessing a child's pain are utilised, resulting in the possibility that not all aspects of a child's pain are assessed. Pain is assessed using the child's self reports or nurses' observations. It has been shown that these are not always appropriate and there is need to use a number of different tools for assessing a child's pain. There is also the need for a validated tool to assess pain in younger children. When referring back to McGrath and Unruh's (1987) definitions of pain measurement and pain assessment, it could be concluded that nurses in the children's A&E department measure pain, but, due to the lack of emphasis which is placed on the different aspects of pain and the limited range of tools which are used, they do not assess pain effectively. In order for pain assessment to be improved, nurses need to be made aware of the different aspects of pain and different tools which are available to assess them in children. This could be initiated by implementing the RCN (1999) guidelines for pain recognition and assessment in children.


"You Needed to Accept the Situation": Resilience of Nursing Home Residents in Times of COVID-19.
The restrictive measures taken by nursing homes during the COVID-19 outbreak in 2020 (e.g., quarantine) may have been important stressors for which residents needed resilience to safeguard their well-being. Based on 30 semi-structured interviews with nursing home residents and close relatives, this study explored the lived experiences with respect to the restrictive measures. The data were collected in psychogeriatric, somatic, and mixed wards in The Netherlands and Flanders, Belgium. The restrictive measures were important stressors for residents, indicated by feelings of loneliness, sadness, and powerlessness. To deal with these measures, residents used various resources, which were determined by factors in the individual (e.g., health), interactional (e.g., possibilities for social interactions) and contextual (e.g. nursing home policy) domains. Because the lived experiences with respect to the restrictive measures seemed to relate to the resilience of nursing home residents, it is crucial to reinforce resources in the individual, interactional, and contextual domains.


Preconception care: advancing from 'important to do and can be done' to 'is being done and is making a difference'.
There is a growing evidence base for preconception care--the provision of biomedical, behavioral and social interventions to women and couples before conception occurs. Firstly, there is evidence that health problems, problem behaviours and individual and environmental risks contribute to poor maternal and child health outcomes. Secondly, there are biomedical, behavioural and social interventions that when delivered beforeconception occurs, effectively address many of these health problems, problem behaviours and risk factors.And thirdly, there is emerging experience of how to deliver these interventions in low and middle income countries (LMIC).The preconception care interventions delivered and whom they are delivered to, will need to be tailored to local realities. The package of preconception care interventions delivered in a particular setting will depend on the local epidemiology, the interventions already being delivered, and the resources in place to deliver additionalinterventions. Although a range of population groups could benefit from preconception care, prioritization based on need and feasibility will be needed.There are both potential benefits and risks associated with preconception care. Preconception care could result in large health and social benefits in LMIC. It could also be misused to limit the autonomy of women and reinforce the notion that the focus of all efforts to improve the health of girls and women should be at improving maternal and child health outcomes rather than at improving the health of girls and women as individuals in their own right.There are challenges in delivering preconception care. While the potential benefits of preconception care programmes could be substantial, extending the traditional Maternal and Child Health package will be both a logistic and financial challenge.We need to help countries set and achieve pragmatic and meaningful short term goals. While our longterm goal for preconception care should be for a full package of health and social interventions to be delivered to all women and couples of reproductive age everywhere, our short-term goals must be pragmatic. This is because countries that need preconception care most are the ones least likely to be able to afford them and deliver them.If we want these countries to take on the additional challenge of providing preconception care while they struggle to increase the coverage of prenatal care, skilled care at birth etc., we must help them identify and deliver a small number of effective interventions based on epidemiology and feasibility.


[Effects of hepatic growth factor on c-kit+Lin- cell proliferation in mouse bone marrow].
To determine the optimal cytokine combinations with hepatic growth factor (HGF) that results in the most significant simultaneous in vitro expansion of cc-kit(+)Lin(-) cells derived from the bone marrow. C-kit(+)Lin(-) cells were isolated from mouse bone marrow using a high-gradient magnetic cell sorting system (MACS) and expanded in the presence of stem cell factor (SCF), FLt-3 ligand (FL), leukemia inhibitor factor (LIF) thrombopoietin (TPO) and different concentrations of HGF for 7days in a liquid culture system. The total cell number and Annexin-V-positive cell number were counted, and the antigen expressions were studied with fluorescence-activated cell sorting (FACS). In each group, c-kit(+)Lin(-) cells were expanded effectively and rapidly by 2 to 8 folds. Addition of 10 ng/ml HGF into SCF+FL+LIF+TPO resulted in the most significant expansion of c-kit(+)Lin(-) and total cells by 8.00 and 45.43 folds, respectively, with cell apoptosis rate of 17.42 %. But as the concentration of HGF increased, the c-kit(+)Lin(-) cells and the apoptosis rate decreased. HGF at10 ng/ml shows optimal synergistic effect with SCF, FL, LIF and TPO in expansion of c-kit(+)Lin(-) cells, and excessive HGF may induce cell differentiation.


Juxtaglomerular apparatus tumor: a rare, surgically correctable cause of hypertension.
Although uncommon, presentation of juxtaglomerular cell tumor is distinct and should allow a correct preoperative diagnosis in most patients. Typical clinical presentations include headaches, polyuria, or isolated, asymptomatic, severe hypertension. The diagnosis of a juxtaglomerular apparatus (JGA) tumor typically results from identification of plasma renin levels two- to sevenfold greater than the normal value. Although JGA tumors are considered benign, with no reports of metastases or recurrence, they are potentially lethal if left untreated. Surgical excision is curative.


Promoter- and cell-specific transcriptional transactivation by the Kaposi's sarcoma-associated herpesvirus ORF57/Mta protein.
The Kaposi's sarcoma-associated herpesvirus (KSHV) Mta protein, encoded by open reading frame 57, is a transactivator of gene expression that is essential for productive viral replication. Previous studies have suggested both transcriptional and posttranscriptional roles for Mta, but little is known regarding Mta's transcriptional function. In this study, we demonstrate that Mta cooperates with the KSHV lytic switch protein, Rta, to reactivate KSHV from latency, but Mta has little effect on reactivation when expressed alone. We demonstrate that the Mta and Rta proteins are expressed with similar but distinct kinetics during KSHV reactivation. In single-cell analyses, Mta expression coincides tightly with progression to full viral reactivation. We demonstrate with promoter reporter assays that while Rta activates transcription in all cell lines tested, Mta's ability to transactivate promoters, either alone or synergistically with Rta, is cell and promoter specific. In particular, Mta robustly transactivates the nut-1/PAN promoter independently of Rta in 293 and Akata-31 cells. Using nuclear run-on assays, we demonstrate that Mta stimulates transcriptional initiation in 293 cells. Rta and Mta physically interact in infected cell extracts, and this interaction requires the intact leucine repeat and central region of Rta in vitro. We demonstrate that Mta also binds to the nut-1/PAN promoter DNA in vitro and in infected cells. An Mta mutant with a lesion in a putative A/T hook domain is altered in DNA binding and debilitated in transactivation. We propose that one molecular mechanism of Mta-mediated transactivation is a direct effect on transcription by direct and indirect promoter association.


FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis.
We have shown previously that fibrin(ogen) binds fibroblast growth factor 2 (FGF-2) and potentiates stimulation of endothelial-cell (EC) proliferation. We have now used 2 FGF-2 mutants differing only in the 5 residues constituting the binding site to characterize the importance of this interaction in angiogenesis. The nonbinding (2212) and binding (221*2) mutants stimulated EC proliferation by 2.2 +/- 0.4-fold and 2.9 +/- 0.3-fold over control, respectively, and both were similar to wild-type (wt) FGF-2 (2.5 +/- 0.3-fold). Proliferation was augmented by fibrinogen to 5.3 +/- 1.2-fold and 4.8 +/- 0.8-fold with wtFGF-2 and 221*2, whereas no augmentation occurred with 2212 and fibrinogen. Using a placental explant model in a fibrin matrix, wtFGF-2 resulted in 2.6 +/- 0.9-fold more growth over control, and 221*2 increased growth 3.3 plus or minus 0.9-fold. Vessel outgrowth with 2212 was minimal and comparable to control. Similarly, fibrinogen potentiated wtFGF-2 or 221*2-mediated angiogenesis in the chicken chorioallantoic membrane model. In a mouse Matrigel implant model, fibrinogen significantly increased angiogenesis with either wtFGF-2 or 221*2, whereas there was no augmentation with 2212. These results demonstrate that binding of FGF-2 to fibrin(ogen) mediated by the 5-residue FGF-2-fibrin(ogen) interactive site is required for augmented angiogenesis.


Myofibroma of mandibular alveolus: A case report.
Phenotypic heterogeneity has been a complex phenomenon lately, fetching attention in tumour pathology. Myofibroblastic differentiation is one such example and, besides, functional heterogeneity contributes to the biological behaviour of the tumours. Myofibroma is a distinctive neoplasm of myofibroblasts with a low incidence rate in the oral cavity. A case of myofibroma in mandibular alveolus in an adult patient is reported here for its rarity and diagnostic dilemma.


Cervical partial hydatidiform molar pregnancy.
Cervical hydatidiform molar pregnancy is an exceedingly rare occurrence that has been reported only twice before. We report a 25-year-old, G4P1D&C2 woman with a positive pregnancy test and vaginal bleeding. A cervical pregnancy with hydatidiform mole was detected on transvaginal ultrasound and color Doppler examinations. Magnetic resonance imaging was used to localize the lesion. Dilatation and curettage was performed and bleeding that was initially brisk ceased after bimanual pressure. Histopathological examination revealed a partial hydatidiform molar pregnancy. Serial beta-hCG measurements showed a decline without need for adjuvant chemotherapy. Conservative fertility-sparing management was successful in this potentially fatal rare case.


[Space-time analysis of over-limit of sodium nitrite in cooked meat products from Hunan Province in 2010-2014].
To determine over-limit status of sodium nitrite in cooked meat products in Hunan Province, and to provide scientific evidence for making health supervision. Methods: In accordance with the national standards for sampling and testing, data were analyzed by classical and spatial statistic methods. Results: The total over-limit rate of sodium nitrite was 5.5% in 731 samples. The relative higher sodium nitrite over-limit rates were Xiangxi Tujia and Miao autonomous prefecture and Zhangjiajie. October and February were the main months in nitrite over-limit. Five regions with over-limit of sodium nitrite in cooked meat products were detected in Hunan. Conclusion: With obvious space-time clustering, over-limit of sodium nitrite in cooked meat products is a common problem particularly in northwest Hunan and Zhuzhou City. Supervision in October should be further strengthened in above-mentioned areas to guarantee the consumers health.


Evaluation of sorption of uranium onto metakaolin using X-ray photoelectron and Raman spectroscopies.
Metakaolin prepared from a natural clay mineral ore of aluminium kaolinite is a promising low cost and high activity aluminosilicate material that has been investigated for studying the sorption behavior of uranium. Here, metakaolin was characterized using X-ray photoelectron spectroscopy (XPS) and the effects of pH, contact time and initial metal ion concentration on its sorption behavior were studied. The sorption process was found to initially be rapid (approximately 60% at time 0 min) but became slower with time; equilibrium was established within 24 h (approximately 80% sorption). The data were applied to study the kinetics of the sorption process. The Langmuir and Dubinin-Radushkevich (D-R) sorption isotherms were used to describe partitioning behavior for the system at room temperature. The binding of metal ions was found to be pH dependent, with optimal sorption occurring at pH 5. The retained metal ions were eluted with 5 mL of 0.1 M HNO(3). Raman spectroscopy and XPS were used to evaluate the sorption mechanism of U(VI).


Does Molecular and Structural Evolution Shape the Speedy Grass Stomata?
It has been increasingly important for breeding programs to be aimed at crops that are capable of coping with a changing climate, especially with regards to higher frequency and intensity of drought events. Grass stomatal complex has been proposed as an important factor that may enable grasses to adapt to water stress and variable climate conditions. There are many studies focusing on the stomatal morphology and development in the eudicot model plant Arabidopsis and monocot model plant Brachypodium. However, the comprehensive understanding of the distinction of stomatal structure and development between monocots and eudicots, especially between grasses and eudicots, are still less known at evolutionary and comparative genetic levels. Therefore, we employed the newly released version of the One Thousand Plant Transcriptome (OneKP) database and existing databases of green plant genome assemblies to explore the evolution of gene families that contributed to the formation of the unique structure and development of grass stomata. This review emphasizes the differential stomatal morphology, developmental mechanisms, and guard cell signaling in monocots and eudicots. We provide a summary of useful molecular evidences for the high water use efficiency of grass stomata that may offer new horizons for future success in breeding climate resilient crops.


Fadrozole reverses cardiac fibrosis in spontaneously hypertensive heart failure rats: discordant enantioselectivity versus reduction of plasma aldosterone.
Reversal of cardiac fibrosis is a major determinant of the salutary effects of mineralocorticoid receptor antagonists in heart failure. Recently, R-fadrozole was coined as an aldosterone biosynthesis inhibitor, offering an appealing alternative to mineralocorticoid receptor antagonists to block aldosterone action. The present study aimed to evaluate the effects of R- and S-fadrozole on plasma aldosterone and urinary aldosterone excretion rate and to compare their effectiveness vs. the mineralocorticoid receptor antagonist potassium canrenoate to reverse established cardiac fibrosis. Male lean spontaneously hypertensive heart failure (SHHF) rats (40 wk) were treated for 8 wk by sc infusions of low (0.24 mg/kg.d) or high (1.2 mg/kg.d) doses of R- or S-fadrozole or by potassium canrenoate via drinking water (7.5 mg/kg.d). At the high dose, plasma aldosterone levels were decreased similarly by R- and S-fadrozole, whereas urinary aldosterone excretion rate was reduced only by S-fadrozole. In contrast, whereas at the high dose, R-fadrozole effectively reversed preexistent left ventricular interstitial fibrosis by 50% (vs. 42% for canrenoate), S-fadrozole was devoid of an antifibrotic effect. The low doses of the fadrozole enantiomers did not change cardiac fibrosis or plasma aldosterone but similarly reduced urinary aldosterone excretion rate. In conclusion, R-fadrozole may possess considerable therapeutic merit because of its potent antifibrotic actions in the heart. However, the observed discordance between the aldosterone-lowering and antifibrotic effects of the fadrozole enantiomers raises some doubt about the mechanism by which R-fadrozole diminishes cardiac collagen and about the generality of the concept of lowering aldosterone levels to treat the diseased heart.


[A plea for a chronobiological approach to diabetes mellitus].
Diabetes mellitus is, in most patients, a multi-metabolic condition disease under fixed standardized conditions. We develop here the advantages of a chronobiological approach, exploring nycthemeral variations in blood pressure, variations in insulin resistance, postprandial changes in blood glucose and postabsorptive variations in blood lipids. Such information can help improve our understanding of the disease, better identify risk and prognosis, and enlighten therapeutic options.


Smoothing things over: the transition from pediatric to adult care for kidney transplant recipients.
Transition is a planned movement of adolescents with chronic physical and medical conditions from child-centered to adult-oriented healthcare systems as opposed to a purely administrative event. To evaluate the transition of pediatric kidney transplant recipients to the adult service at Guy's Hospital between 2000 and 2001 as compared with best practice from the literature, and to establish client satisfaction with the process. Data were collected by means of a retrospective review of case notes, clinician interview, and a patient satisfaction questionnaire, and analyzed by a single reviewer. Sixteen cases were analyzed with respect to their progress over the period of 1 year before and 1 year after transfer by looking at markers of adherence; a clinician's subjective assessment of overall graft stability before, during, and after transfer; and whether subjects chose to attend the transitional clinic. There was no qualitative difference in adherence or control among the patients who experienced the transitional clinic and those who did not. Patients who were considered stable and adherent before transition were not necessarily the same following transfer and vice versa. Patients who experienced the transitional clinic were not more satisfied as a group, although 9 of 11 thought their transition was "OK" or better. This is an extremely challenging area of pediatric nephrology; all patients need a high level of support. Services cannot be targeted to high-risk groups.


Postural Control in Deaf Children.
This cross-sectional study aimed to determine the reliability of static control evaluation with Synapsys Posturography System (SPS, Marseille, France) and to compare the static postural control of deaf children with typically developing children. This study was conducted in 2 phases on 81 children of 7 to 12 years old in Tehran schools. The first phase examined the reliability of static balance evaluation with SPS. In this phase, a total of 12 children with typical development were evaluated and then do a re-test 1 week later. In the second phase, 30 children with profound sensorineural hearing loss (SNHL) and high risk in their balance (selected from Baghcheban Schools for the Deaf) as the experimental group, and 37 children with typical development (selected randomly from 2 primary schools for girls and boys in District 12 of Tehran Department of Education) as control group were enrolled in the study. They were all placed under sensory organization test evaluation. Based on the results of intraclass correlation coefficient (ICC), the unilateral random effects model, test-retest reliability in different sensory conditions, the moderate to excellent results were obtained (ICC between 0.68 and 0.94). Also, the mean displacement of pressure center in all sensory conditions, the limits of stability (LOS) area, the overall balance scores, and scores for balance sensory ratio (except the somatosensory ratio) of children with typical development were better than the deaf peers (P˂0.05). The SPS has acceptable reliability to evaluate static posture in children between the ages of 7 and 12 years. Furthermore, deaf children as compared to children with typical development had a lower static postural control in all sensory conditions. This finding confirms the need to examine the postural control for identifying the extent of sensory deficit that has caused poor balance function, and also the need for early intervention to address the balance deficit in deaf children.


Proliferation of arterial smooth muscle: glucocorticoid effect.
Tritiated thymidine radioautography was employed to study the effect of glucocorticoids on smooth muscle proliferation in rabbit arteries. In the aorta and pulmonary artery of rabbits with cholesterol atherolsclerosis, labelled cell counts showed that these steroids decrease the deoxyribonucleic acid synthesis in the intimal plaques. The inhibitory effect on thymidine uptake was found to be dose dependent and closely related to the antiinflammatory potency of the steroid tested. In another set of experiments the smooth muscle proliferation occurring in the rabbit carotid artery after disendothelization was studied. In these normolipemic animals the inhibition of DNA synthesis was particularly evident in the medial smooth muscle cell; concomitantly, in steroid-treated animals the myointimal thickening in the denuded area was less prominent. It is concluded that very likely the glucocorticoid effect on the artery is due to a direct interaction of the steroid with smooth muscle cells.


The effect of troglitazone on plasma homocysteine, hepatic and red blood cell S-adenosyl methionine, and S-adenosyl homocysteine and enzymes in homocysteine metabolism in Zucker rats.
We studied the effect of troglitazone on the plasma concentrations of homocysteine (tHcy), the erythrocyte and hepatic concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and the hepatic activities of cystathionine-beta-synthase (C beta S) and methylenetetrahydrofolate reductase (MTHFR) in lean and fatty Zucker rats (a model of insulin resistance). Four groups of female Zucker rats were studied. Troglitazone (200 mg/kg) was administered by gavage daily for 3 weeks to lean and fatty Zucker rats. The other 2 groups served as controls. The blood parameters were determined at days 0, 10, and 21. The hepatic SAM and SAH concentrations and MTHFR and C beta S were measured in the 3-week liver samples. Plasma homocysteine fell significantly in all troglitazone-treated animals from a mean +/- SD of 7.6 +/- 1.5 micromol/L to 4.5 +/- 1.1 micromol/L (P <.02) but not in control animals (5.7 +/-1.8 micromol/L to 5.9 +/- 1.8 micromol/L). The decreases induced by troglitazone in homocysteine were seen in both the lean and the fatty Zucker rats. This was accompanied by significant rises in the hepatic concentrations of SAH and SAM + SAH. In addition, a significant decline in the hepatic SAM/SAH ratio was observed. The mean +/- SD hepatic C beta S (expressed as nmol of cystathionine formed at 37 degrees C) in the troglitazone-treated rats was 1,226 +/- 47 nmol/h/mg protein, which was significantly higher than that in the control group (964 +/- 64 nmol/h/mg protein; P =.03). We conclude that troglitazone lowers plasma homocysteine in insulin-resistant animals. The homocysteine-lowering effects of troglitazone may be mediated in part by a shift in the concentrations of tHcy and its related metabolites from the blood to the liver as well as by an upregulation of hepatic C beta S activity. These data support the hypothesis that insulin may regulate homocysteine metabolism through regulation of hepatic C beta S activity, although activity of other hepatic enzymes not studied here may also contribute to these observations.


Hyperuricemia and tumor lysis syndrome in children with non-Hodgkin's lymphoma and acute lymphoblastic leukemia.
This study aimed to examine the incidence, clinical characteristics, and outcome of hyperuricemia and tumor lysis syndrome (TLS) in children with non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL). This retrospective study included data from 327 patients (113 NHL and 214 ALL). Hyperuricemia occurred in 26.5% and 12.6% of the patients with NHL and ALL, respectively. The corresponding figures for TLS were 15.9% and 0.47% (p=0.001). All hyperuricemic NHL patients had advanced disease and renal involvement was present in 53%. All hyperuricemic ALL patients had a leukocyte count >50,000 mm3 at the time of diagnosis. Among the hyperuricemic NHL and ALL patients, 96.6% and 66.6% had LDH ≥500 UI/L, respectively. Treatment consisted of hydration and allopurinol; none of the patients received urate oxidase. Among the patients that developed TLS, 26.3% had laboratory TLS, 42.1% had grade I or II TLS, and 31.6% had grade III or IV TLS. Uric acid levels returned to normal after a mean period of 3.5±2.5 and 3.05±0.8 d in NHL and ALL groups, respectively. In all, 7% of the patients with hyperuricemia required hemodialysis. None of the patients died. In this series the factors associated with a high-risk for TLS were renal involvement in NHL and high leucocyte count in ALL. Management with allopurinol and hydration was effective in this group of patients with high tumor burden.


Endovascular treatment of chronic mesenteric ischemia.
Endovascular procedure is frequently used as an alternative to surgical bypass in aortic atherosclerotic lesions. Two rare cases of chronic mesenteric ischemia treated with a stent implantation are reported. The patients were a 72-year-old woman and a 57-year-old woman. They presented with severe abdominal pain after meals, repeatedly. Angiography revealed severe stenosis and occlusion of the super mesenteric artery (SMA). Endovascular treatment was initially and technically successful in both patients. A Palmaz stent was deployed in the ostium lesion of the SMA for both cases. Completion angiography showed successful recanalization of the SMA without any complication and with satisfactory distal flow. The patients' symptoms were alleviated. They remained asymptomatic after stent implantation. Primary stenting may be considered a viable alternative to conventional surgery in carefully selected patients with chronic mesenteric ischemia due to SMA stenosis.


Marginal Maternal Zinc Deficiency Produces Liver Damage and Altered Zinc Transporter Expression in Offspring Male Rats.
The aim of this study was to investigate how zinc deficiency and supplementation affect liver markers including autotaxin, kallistatin, endocan, and zinc carrier proteins ZIP14 and ZnT9 in rats exposed to maternal zinc deficiency. Additionally, the study aimed to assess liver tissue damage through histological examination. A total of forty male pups were included in the research, with thirty originating from mothers who were given a zinc-deficient diet (Groups 1, 2, and 3), and the remaining ten born to mothers fed a standard diet (Group 4). Subsequently, Group 1 was subjected to a zinc-deficient diet, Group 2 received a standard diet, Group 3 received zinc supplementation, and Group 4 served as the control group without any supplementation. Upon completion of the experimental phases of the study, all animals were sacrificed under general anesthesia, and samples of liver tissue were obtained. The levels of autotaxin, kallistatin, endocan, ZIP 14, and ZnT9 in these liver tissue samples were determined using the ELISA technique. In addition, histological examination was performed to evaluate tissue damage in the liver samples. In the group experiencing zinc deficiency, both endocan and autotaxin levels increased compared to the control group. With zinc supplementation, the levels of endocan and autotaxin returned to the values observed in the control group. Similarly, the suppressed levels of kallistatin, ZIP14, and ZnT9 observed in the zinc deficiency group were reversed with zinc supplementation. Likewise, the reduced levels of kallistatin, ZIP14, and ZnT9 seen in the zinc deficiency group were rectified with zinc supplementation. Moreover, the application of zinc partially ameliorated the heightened liver tissue damage triggered by zinc deficiency. This study is the pioneering one to demonstrate that liver tissue dysfunction induced by a marginal zinc-deficient diet in rats with marginal maternal zinc deficiency can be alleviated through zinc supplementation.


Process Evaluation of an Application-Based Salt Reduction Intervention in School Children and Their Families (AppSalt) in China: A Mixed-Methods Study.
Salt reduction is a cost-effective, and rather challenging public health strategy for controlling chronic diseases. The AppSalt program is a school-based multi-component mobile health (mhealth) salt reduction program designed to tackle the high salt intake in China. This mixed-methods process evaluation was conducted to investigate the implementation of this program across sites, identify factors associated with the implementation, and collect evidence to optimize the intervention design for future scale-up. Mixed methods were used sequentially to collect data regarding five process evaluation dimensions: fidelity, dose delivered, dose received, reach, and context. Quantitative data were collected during the intervention process. Participation rate of intervention activities was calculated and compared across cities. The quantitative data was used for the selection of representative intervention participants for the qualitative interviews. Qualitative data were collected in face-to-face semi-structured interviews with purposively selected students (n = 33), adult family members (n = 33), teachers (n = 9), heads of schools (n = 9), key informants from local health, and education departments (n = 8). Thematic analysis technique was applied to analyze the interview transcripts using NVivo. The qualitative data were triangulated with the quantitative data during the interpretation phase. The total number of families recruited for the intervention was 1,124. The overall retention rate of the AppSalt program was 97%. The intervention was implemented to a high level of fidelity against the protocol. About 80% of intervention participants completed all the app-based salt reduction courses, with a significant difference across the three cities (Shijiazhuang: 95%; Luzhou: 73%; Yueyang: 64%). The smartphone app in this program was perceived as a feasible and engaging health education tool by most intervention participants and key stakeholders. Through the interviews with participants and key stakeholders, we identified some barriers to implementing this program at primary schools, including the left-behind children who usually live with their grandparents and have limited access of smartphones; perceived adverse effects of smartphones on children (e.g., eyesight damage); and overlooked health education curriculum at Chinese primary schools. This process evaluation demonstrated the feasibility and acceptability of using smartphone applications delivered through the education system to engage families in China to reduce excessive salt intake. The AppSalt study was registered at www.chictr.org.cn, identifier: ChiCTR1800017553. The date of registration is August 3, 2018.


Nonlinear X waves in second-harmonic generation: experimental results.
X waves, spatiotemporal generalization of the monochromatic Bessel- (or Durnin-) type beams, are known in linear acoustic, microwave and optics for their unique property of defeating both spatial and temporal spreadings. Recently, we brought to the attention that X-type waves are also the key to understand the spatiotemporal dynamics observed in the nonlinear (high intensity) regime. Indeed, X waves represent the normal-propagation mode for a wide class of parametric interactions described by hyperbolic nonlinear models featuring spatial self-focusing and temporal self-broadening. Here, we provide a complete and detailed description of the experiment in which the spontaneous appearance of X waves has been observed. The experiment concerns frequency doubling of a 170-fs, 50-microm standard laser wave packet in a 22-mm lithium triborate crystal, tuned for second-harmonic generation with positive phase mismatch, positive group-velocity dispersion, and large group-velocity mismatch. Conventional beam-profile and autocorrelation measurements at the crystal output face show evidence of spatiotemporal self-trapping. The characterization of the free-space propagation reveals sub-Gaussian diffraction and pulse broadening, consistent with the presence of angular dispersion. Space-resolved autocorrelations indicate the generation of an X-type profile.


Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis.
A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone.


Physical heterogeneity increases biofilm resource use and its molecular diversity in stream mesocosms.
Evidence increasingly shows that stream ecosystems greatly contribute to global carbon fluxes. This involves a tight coupling between biofilms, the dominant form of microbial life in streams, and dissolved organic carbon (DOC), a very significant pool of organic carbon on Earth. Yet, the interactions between microbial biodiversity and the molecular diversity of resource use are poorly understood. Using six 40-m-long streamside flumes, we created a gradient of streambed landscapes with increasing spatial flow heterogeneity to assess how physical heterogeneity, inherent to streams, affects biofilm diversity and DOC use. We determined bacterial biodiversity in all six landscapes using 16S-rRNA fingerprinting and measured carbon uptake from glucose and DOC experimentally injected to all six flumes. The diversity of DOC molecules removed from the water was determined from ultrahigh-resolution Fourier Transform Ion Cyclotron Resonance mass spectrometry (FTICR-MS). Bacterial beta diversity, glucose and DOC uptake, and the molecular diversity of DOC use all increased with increasing flow heterogeneity. Causal modeling and path analyses of the experimental data revealed that the uptake of glucose was largely driven by physical processes related to flow heterogeneity, whereas biodiversity effects, such as complementarity, most likely contributed to the enhanced uptake of putatively recalcitrant DOC compounds in the streambeds with higher flow heterogeneity. Our results suggest biophysical mechanisms, including hydrodynamics and microbial complementarity effects, through which physical heterogeneity induces changes of resource use and carbon fluxes in streams. These findings highlight the importance of fine-scale streambed heterogeneity for microbial biodiversity and ecosystem functioning in streams, where homogenization and loss of habitats increasingly reduce biodiversity.


Utilization of the nitrate reductase enzymatic pathway to reduce enteric pathogens in chickens.
Previous reports have shown that some bacteria, including Salmonella, use a dissimilatory nitrate reductase enzyme pathway (NREP) in anaerobic environments. This enzyme reduces nitrate to nitrite and has been shown to cometabolize chlorate to cytotoxic chlorite. The present investigations were performed to evaluate the susceptibility of a competitive exclusion culture (CE) to the experimental chlorate product (ECP). A commercially available CE product was evaluated for its nitrate reductase activity and therefore its chlorate sensitivity. Individual isolates (in triplicate) were cultured in 10 mL of Viande Levure broth containing 5 mM sodium nitrate or 10 mM sodium chlorate. Bacterial growth (optical density at 625 nm) was measured and 1-mL aliquots were removed concurrently for colorimetric determination of nitrate content at 0, 3, 6, and 24 h. Of the 15 different facultative strains, 11 had slight NREP utilization, 3 had moderate NREP utilization, and the remainder were NREP negative (with slight and moderate NREP utilization: >0.1 to <1.0 mM and >1.0 mM nitrate used within 6 h, respectively). Of the obligate anaerobes evaluated, 3 had slight NREP utilization and the remainder were NREP negative. In vivo studies utilizing both products (CE and ECP) in a horizontal transmission challenge model (seeders + contacts) showed significant reductions in Salmonella from 5.37 to 1.76 log10 cfu/g and 3.94 to 0.07 log10 cfu/g, respectively. The combined effect of the CE culture and an ECP are effective in killing these food-borne pathogens.


[Light-chain deposition disease is a hematologic problem].
To analyze clinical and laboratory data and treatment results in patients with light-chain deposition disease (LCDD). Nine patients with LCDD and kidney injury were examined. The diagnosis was based on the results of light and immunofluorescence microscopy of renal biopsy specimens. All the patients received bortezomib, cyclophosphamide, and dexamethasone (VCD) induction therapy. Six patients were diagnosed with multiple myeloma; in 3 patients LCDD was considered within monoclonal gammopathy manly involving the kidney. By the initiation of therapy, all the patients were diagnosed as having chronic kidney disease (Stage III (n=2), Stage IV (n=2), and dialysis-related renal failure (n=5)). After the VCD treatment, 7 of 9 patients achieved a hematologic response. Second-line therapy with lenalidomide proved to be effective in the other 2 cases. Five patients achieved complete remission; 3 had a very good partial remission. Thereafter, 2 patients received high-dose melphalan chemotherapy and autologous hematopoietic stem cell transplantation. Better renal function was noted in only 2 cases. Despite the high efficiency of therapy aimed to reduce monoclonal light chains; improved renal function was observed in only 2 (22%) patients. Such low rates of a renal response were due to the late initiation of therapy.