Incorporating Exercise Efficiency to Evaluate the Accessibility and Capacity of Medical Resources in Tibet, China.
Accessibility and capacity of medical resources are key for the health care and emergency response, while the efficiency of the medical resources is very much limited by hypoxia in Tibet, China. Through introducing exercise efficiency, this study explores the accessibility of township residence to county-ship medical resources in Tibet using weighted mean travel time (WMT), and evaluates the medical capacity accordingly. The results show that: 1) the average travel time of township residence to county-level hospital is around 2 h by motor vehicle in Tibet. More than half of the population can not reach the county-ship hospital within 1 h, 33.24% of the population can not reach within 2 h, and 3.75% of the population can not reach within 6 h. 2) When considering the catchment of the medical resources and the population size, the WMT of the county-ship medical resources ranges from 0.25 h to 10.92 h. 3) After adjusted by travel time and exercise efficiency, the county-ship medical capacity became more unequal, with 38 out of 74 counties could not meet the national guideline of 1.8 medical beds per 1000. 4) In total, there are 17 counties with good WMT and sufficient medical resources, while 13 counties having very high WMT and low capacity of medical resources in Tibet. In the end, suggestions on medical resources relocation and to improve the capacity are provided. This study provides a method to incorporate exercise efficiency to access the accessibility and evaluate medical capacity that can be applied in high altitude ranges. Supplementary material is available in the online version of this article at 10.1007/s11769-022-1321-1.


Therapeutic Drug Monitoring and Nephrotoxicity of Teicoplanin Therapy in Chinese Children: A Retrospective Study.
This study aims to 1) describe the distribution characteristics of teicoplanin trough concentration (C min) and explore the related influencing factors and 2) evaluate the nephrotoxicity of teicoplanin in children. A cohort of children who were treated with teicoplanin intravenously were included in this retrospective study. Regression analysis was performed to explore the factors associated with the fluctuations of teicoplanin C min and the development of nephrotoxicity. Classification and regression tree analysis was used to identify the population at high risk for teicoplanin nephrotoxicity. A total of 269 plasma samples from 186 children were collected. Underexposure (C min < 10 mg/L) was documented in 52.7% of cases. The C min/dose after administering the loading dose was strongly associated with age (P = 0.008), weight (P = 0.039), and serum creatinine (P = 0.022). The C min/dose after administering the maintenance dose was strongly associated with gender (P = 0.014) and serum creatinine (P = 0.006). C min (P = 0.012) and the concomitant treatment with amphotericin B (P = 0.001) were the independent risk factors for teicoplanin-related nephrotoxicity. Children who were concomitantly treated by amphotericin B with teicoplanin C min > 9.81 mg/L or patients with teicoplanin C min > 21.94 mg/L were at high risk for nephrotoxicity. The fluctuations of teicoplanin C min could be affected by age, weight, gender, and serum creatinine. C min and concomitant treatment with amphotericin B were the independent risk factors for nephrotoxicity. We suggested that the therapeutic drug monitoring of teicoplanin should be performed in children.


Soil zinc content, groundwater usage, and prostate cancer incidence in South Carolina.
Prostate cancer (PrCA) incidence in South Carolina (SC) exceeds the national average, particularly among African Americans (AAs). Though data are limited, low environmental zinc exposures and down-regulation of prostatic zinc transporter proteins among AAs may explain, in part, the racial PrCA disparity. Age-adjusted PrCA rates were calculated by census tract. Demographic data were obtained from the 1990 census. Hazardous waste site locations and soil zinc concentrations were obtained from existing federal and state databases. A geographic information system and Poisson regression were used to test the hypothesis that census tracts with reduced soil zinc concentrations, elevated groundwater use, or more agricultural or hazardous waste sites had elevated PrCA risks. Census tracts with high groundwater use and low zinc concentrations had higher PrCA rate ratios (RR: 1.270; 95% confidence interval: 1.079, 1.505). This effect was not more apparent in areas populated primarily by AAs. Increased PrCA rates were associated with reduced soil zinc concentrations and elevated groundwater use, although this observation is not likely to contribute to SC's racial PrCA disparity. Statewide mapping and statistical modeling of relationships between environmental factors, demographics, and cancer incidence can be used to screen hypotheses focusing on novel PrCA risk factors.


Single polymer-based ternary electronic memory material and device.
A ternary polymer memory device based on a single polymer with on-chain Ir(III) complexes is fabricated by combining multiple memory mechanisms into one system. Excellent ternary memory performances-low reading, writing, and erasing voltages and good stability for all three states-are achieved.


Heavy metal accumulation (lead and cadmium) and ion exchange in three species of Sphagnaceae : I. Main principles of heavy metal accumulation in Sphagnaceae.
Three different species of Sphagnum mosses originating from a bog ("Hochmoor") were examined with respect to their behaviour of accumulation of heavy metal ions lead and cadmium. A strong bond of double charged Pb could be found independent of the Sphagnum species. When competitive reactions were performed in test solutions, with two ions (Pb2+ and one alkali or one earthalkali ion) or three (Pb2+ and one earthalkali and one alkali ion) Pb2+ was always accumulated too. This leads to a suppression of exchange of the other ions. Cadmium is by far less strongly bound than lead. Cadmium was tested in combination with two or three ions as was done for lead. The behaviour of cadmium adsorption is similar to that of calcium. For a number of ions typical tendencies were observed, which give insight in the quantity and strength of their binding to the exchanging material. The following series of accumulation was found: Pb2+>Cd2+≥Ca2+>Mg2+>K+>Na+≥NH inf4sup+ . (Accumulation was determined in test solutions containing each ion in the concentration 0.01N.) Differences in this series selectivity could not be found within the three Sphagnum species. But there exist typical differences in the total amount of adsorbed ions per unit dry weight. This species specific value corresponds with total capacities for ion exchange of the three species. Furthermore acid strength as well as pH-dependence of the ion exchanging Sphagnum material were investigated. Its physico-chemical behaviour may be described as that of a weak acid polyelectrolyte with variable charge, depending on ionic strength.


Nicotinic cholinergic normalization of amphetamine-induced loss of auditory gating in freely moving rats.
The impairment in normal sensory processing which is usually observed in schizophrenics has been demonstrated using a paired-stimulus paradigm. Normal individuals show a diminished midlatency evoked potential response to the second of a pair of clicks given at a 0.5-s interval. This phenomenon is termed auditory "gating". Schizophrenics routinely fail to suppress their response to the second click in this paradigm; thus, they do not gate. Heavy tobacco use is common among schizophrenics and it has recently been shown that nicotine causes a transient normalization of auditory gating in these individuals. Our laboratory has been utilizing animal models to investigate the sensory deficit observed in schizophrenia. In the present study, rats were administered amphetamine to produce a schizophrenia-like loss of auditory gating. They were then given nicotine, which resulted in a dose-dependent normalization of the amphetamine-induced loss of gating. This effect was blocked by concurrent central administration of d-tubocurarine. Neither nicotine nor d-tubocurarine had any effect on auditory gating when administered alone. These data are in agreement with the human studies showing normalization of auditory gating with nicotine administration and suggest a possible role for the nicotinic cholinergic receptor in the modulation of auditory gating in the rat model.


Inhibitory effect of a spicamycin derivative, KRN5500, on the growth of hepatic metastasis of human colon cancer-producing tissue polypeptide antigen.
The inhibitory effect of KRN5500, a spicamycin derivative, on the growth of hepatic metastasis of the tissue polypeptide antigen (TPA)-producing human colon cancer COL-1 was examined in severe combined immunodeficient (SCID) mice. Prior to this chemotherapeutic study, we confirmed the high correlation coefficient (r = 0.86, P < 0.01) between plasma TPA levels in athymic nude mice bearing COL-1 and tumor volume. In the chemotherapy of experimental hepatic metastasis induced by intrasplenic injection of COL-1 cells, KRN5500 at 12 mg/kg per day was administered i.v. three times at 4-day intervals. From the start of chemotherapy (day 1), plasma TPA levels in the mice were significantly decreased from 8332 U/l to a minimum of 494 U/l on day 16 and were within the range for intact SCID mice (409-634 U/l). The mean tumor weight was 4.87 g in the liver of untreated mice on day 19 and 0.74 g, in the liver of KRN5500-treated mice, a significant difference, representing a tumor growth inhibition rate of 85%. These results suggest the usefulness of TPA as a tumor marker in an experimental xenograft model. The chemotherapeutic efficacy of KRN5500 against experimental hepatic metastasis indicates that it may be a useful drug for the treatment of patients with hepatic metastases of colon cancer.


High-temperature and stress response behavior of femtosecond laser pulses inscribed eccentric fiber Bragg gratings.
Eccentric fiber Bragg grating (EFBG) is inscribed in standard communication single-mode fiber using femtosecond laser pulses, and the temperature and strain sensing characteristics are experimentally demonstrated and analyzed. The EFBG exhibits strong thermal stability and good robustness in high-temperature measurement up to 1000 °C, and undergoes different thermal sensitivities during Bragg peak and the strong resonance coupled cladding spectral comb. The temperature sensitivity linearly increases with respect to the effective index of the resonant modes. Such a situation also occurs in axial strain measurement. These characteristics are of high interest for multiparametric sensing at high temperatures.


[Predictive factors for conversion of transurethral resection of the prostate to open prostatectomy].
To evaluate the factors for the conversion of transurethral resection of the prostate (TURP) to open prostatectomy and to provide clinical evidence for surgical options. From January 1997 to March 2005, we performed 1 086 TURP and made retrospective analyses of 11 risk factors concerning the demographics, clinical history, laboratory data, ultrasound results, and intraoperative complications of the patients. In addition, multivariate logistic regression was used to determine those variables predicting the conversion of TURP. Thirty-nine (3.59%) of the TURP cases required conversion, mostly because of uncontrollable hemorrhage (71.79%). Multivariate analyses showed that a prostate volume > 85.2 ml (OR = 2.568, P < 0.01), intraoperative slit of capsula prostatic (OR = 1.916, P < 0.01) and a second midstream bladder specimen (VB2) white blood cell count of the urine > 13.5/HP (OR = 1.486, P < 0.01) predicted the conversion to open prostatectomy. Benign prostatic hyperplasia (BPH) patients with a huge prostate and those with intraoperative slit of capsula prostatic undergoing TURP are more likely to be converted. And uncontrollable hemorrhage, huge prostate and poor endoscopic vision are the major reasons for the conversion.


Photosynthetic oxygen evolution from hydrogen peroxide.
A study was made of the interactions of flash-illuminated chloroplasts with hydrogen peroxide. We conclude: 1. The oxygen precursor system can be reduced beyond the S0 state to an S-1 state, which can be oxidized to S0 by a single flash. 2. In the dark, a two-electron donation by H2O2 takes place which reduces S2 to S0 and S1 to S-1. 3. At the same time, two-electron oxidations by H2O2 re-form, S2 from S0 and S1 from S-1. 4. The catalase-like activity due to this cyclic oxidation and reduction of the S enzyme is higher with the S2 in equilibrium S0 couple than with the S1 in equilibrium S-1 couple. Another process, however, is responsible for most of the O2 evolution from H2O2 in the light. Our evidence indicates that this process: (1) is independent of the S states and insensitive to Tris washing, (2) turns over rapidly in high concentrations of peroxide, (3) yields 1 O2 per electron passing through system II; (4) dismutates two H2O2 molecules, so that there is no net consumption of 'holes'.


Local delivery versus intracoronary infusion of abciximab in patients with acute coronary syndromes.
We investigated whether local abciximab delivery to the site of intracoronary thrombus is more effective than intracoronary bolus infusion in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention and downstream clopidogrel administration. The intracoronary route of administration does not allow an optimal contact between the plaque components and abciximab, which is rapidly washed out by the coronary flow. A total of 50 patients with ACS and a significant lesion in the culprit artery indicative of local thrombosis were randomly assigned to receive local intracoronary delivery of abciximab through a dedicated perfusion catheter or intracoronary infusion through the guiding catheter. The primary end point was the change in thrombus score after angioplasty by optical coherence tomography. After the intervention, the mean percentage change of the thrombus score was significantly higher among patients of the local delivery group compared with those of the intracoronary infusion group (33.8% vs. 3.9%, p = 0.002). Post-procedural corrected Thrombolysis in Myocardial Infarction frame count was shorter in the local delivery group compared with the intracoronary infusion group (15.3 ± 10.2 vs. 21.1 ± 9.9, p = 0.049). Procedure-related myocardial infarction was observed in 10% and 43% of patients in the local delivery and intracoronary infusion groups, respectively (p = 0.018). At 1 year, MACE were observed in 5.9% and 27.2% of patients in the local delivery and intracoronary infusion groups, respectively (p = 0.046). Local intracoronary delivery of abciximab by means of a dedicated perfusion catheter reduces thrombus burden with the potential to improve coronary microcirculation.


[Analysis of motor development within the first year of life: 3-D motion tracking without markers for early detection of developmental disorders].
Children with motor development disorders benefit greatly from early interventions. An early diagnosis in pediatric preventive care (U2-U5) can be improved by automated screening. Current approaches to automated motion analysis, however, are expensive, require lots of technical support, and cannot be used in broad clinical application. Here we present an inexpensive, marker-free video analysis tool (KineMAT) for infants, which digitizes 3‑D movements of the entire body over time allowing automated analysis in the future.Three-minute video sequences of spontaneously moving infants were recorded with a commercially available depth-imaging camera and aligned with a virtual infant body model (SMIL model). The virtual image generated allows any measurements to be carried out in 3‑D with high precision. We demonstrate seven infants with different diagnoses. A selection of possible movement parameters was quantified and aligned with diagnosis-specific movement characteristics.KineMAT and the SMIL model allow reliable, three-dimensional measurements of spontaneous activity in infants with a very low error rate. Based on machine-learning algorithms, KineMAT can be trained to automatically recognize pathological spontaneous motor skills. It is inexpensive and easy to use and can be developed into a screening tool for preventive care for children.


[Breast morphology in Turner's syndrome. A prospective multicentre clinical study about 21 cases].
The Turner's syndrome encompassed several conditions, of which monosomy X (absence of the entire sex chromosome X) is most common. It is a chromosomal abnormality in which all or part of the sex chromosomes X is absent. Typical females have two X chromosomes, but in Turner's syndrome, one of those sex chromosomes is missing or presents abnormalities. Patients show a shield shaped thorax with thick and bulging chest, breast hypotrophy and widely spaced nipples. The objective of this study was to characterize the breast abnormalities observed in Turnerian. We describe a prospective multicentric study (August 2007-March 2008) on 21 nullipar patients, ranging from 16 to 35 years old. Six were monosomic and 14 were Turner mosaic (in this case the chromosome is missing in some cells but not others), 19 were treated with estrogens and progestatives. This study was achieved through the use of clinical examinations including body, waist, hips (BWH) measurements and photography. The statistical method involved a descriptive analysis, linear correlation calculations and student test. The breast morphology appears to be quite closed to that of the general woman population, but with average thorax volume more bulky mainly in the anteroposterior zone, and with more reduced breast volumes. No specific abnormalities in the chest development were observed. No differences in the hypotrophy, hypertrophy, and normal breast volume repartition were observed between monosomic and mosaic patients. The self-satisfaction index on the breast look is quite low, patients mainly complain about breast hypotrophy. Nevertheless, these results are not representative of the whole turnerians, since this study address only to volunteer patients and we cannot exclude possible distortions. In contrast to common beliefs, we don't have observed any increase of the average of the internipple space; this observation is in good agreement with the most recent published literature works, which report only an apparent increase of this intermamelonary distance versus the thoracic width (in front view), probably caused to an optical distortion effect.


The feasibility of quantitative parameters of lymphoscintigraphy without significant dermal backflow for the evaluation of lymphedema in post-operative patients with breast cancer.
We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy. We evaluated 47 lymphoscintigraphies without dermal backflow in patients with lymphedema who received a mastectomy and axillary dissection or sentinel lymph node dissection for invasive ductal carcinoma of the breast. The quantitative asymmetry indices (QAIs) of both arms were calculated for each axilla, upper arm, forearm, and the whole arm. The QAI was defined as the radiopharmaceutical uptake ratio of the affected side to the unaffected side. Arm circumference was measured at four locations per arm to identify the maximal circumference difference (MCD) between affected and unaffected sides. The total and forearm QAIs of each side arm were significantly higher in the group with above moderate stage lymphedema compared with the mild stage group. Previous radiotherapy also had a significant effect on radiotracer retention expressed as QAI. The MCD was significantly correlated with QAI values of the forearm and the whole arm. The QAI of axillary areas was not significantly correlated with circumferential measurements of the arm. The QAIs have significant value for the diagnosis and severity of lymphedema and may therefore potentially be used as an objective tool for the assessment of lymphedema.


Amine metabolites and neuroendocrine responses related to depression and suicide.
5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the lumbar cerebrospinal fluid of 57 drug-free female patients with DSM-III diagnoses of major unipolar or bipolar depression (n = 14), schizophrenic disorder (n = 18), alcohol dependence (n = 13) and a group of other disorders (n = 12). Following lumbar punctures all patients received a dexamethasone suppression test. Fourteen patients had attempted suicide immediately before admission, 4 of them by violent methods. Severity of depression, independent of the diagnosis, was assessed in every patient on the 24-item Hamilton scale. No significant differences in means and variances of amine metabolite or postdexamethasone plasma cortisol concentrations were found among the diagnostic subgroups. Suicidal patients, and in particular those who used violent methods, tended to have lower 5-HIAA, but not HVA, in their CSF; they also more often had non-suppression of cortisol after dexamethasone. Since correlation matrices in the diagnostic subgroups were homogeneous, we calculated partial correlations for the total group: here suicide attempts but not depression, seemed to be significantly correlated with CSF 5-HIAA. Thyrotropin stimulation tests were administered to 6 patients: maximal TSH responses showed a borderline significant correlation with CSF 5-HIAA, and a significant correlation with severity of depression. Neither suicide nor postdexamethasone cortisol levels showed any relation to maximal TSH changes.


Solubilization and characterization of a ouabain-sensitive protein from transverse tubule membrane-junctional sarcoplasmic reticulum complexes (TTM-JSR) in cat cardiac muscle.
A new glycoprotein of 31,500 dalton, which has a high affinity for ouabain, and is independent of (Na+-K+)-ATPase, was solubilized from transverse tubule membrane and junctional sarcoplasmic reticulum complexes (TTM-JSR) of cat cardiac muscle. This protein could be extracted only in small amounts from sarcolemma-plasma membrane (SLM-PL) fragments, suggesting that it indeed originates from the TTM-JSR.


A real-world study of ART in France (REOLA) comparing a biosimilar rFSH against the originator according to rFSH starting dose.
Since the first launch of a biosimilar recombinant follicle stimulating hormone (rFSH), Bemfola®, in Europe in 2014, it has been possible to study in routine clinical care throughout France the effectiveness of a biosimilar rFSH including according to different rFSH starting doses. REOLA was a non-interventional, retrospective, real world study using anonymized data from 17 Assisted Reproductive Technology (ART) centres' data management systems across France including 2,319 ART ovarian stimulation cycles with Bemfola® and 4,287 ART ovarian stimulation cycles with Gonal-f®. For both products, four populations were studied according to starting dose of rFSH: < 150 IU, 150 - 224 IU, 225 - 299 IU and ≥ 300 IU. The primary endpoint was the cumulative live birth rate (cLBR) per commenced ART ovarian stimulation cycle including all subsequent fresh and frozen-thawed embryo transfers starting during a follow up period of at least 1 year following oocyte retrieval. A direct relationship of increasing rFSH starting dose with increasing age, increasing basal FSH, decreasing AMH and increasing body mass index was noted. No clinically relevant differences were seen in all outcomes reported, including the cLBR, between Bemfola® and Gonal-f®, but for both drugs, an association was seen with increasing rFSH starting dose and decreasing cLBR. The REOLA study demonstrates that the cLBR with Bemfola® is very similar to Gonal-f® across all patient subpopulations. The cLBR is inversely related to the rFSH starting dose irrespective of the drug used, and the REOLA study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting.


Parathyroid carcinoma in a 13-year-old girl with a long-term survival.
Parathyroid carcinoma as a cause of primary hyperparathyroidism in children is extremely rare. We report a case of parathyroid carcinoma which occurred in a 13-year-old girl who survived for more than 45 years after the first operation. A woman was admitted to our hospital for the treatment of recurrent parathyroid carcinoma in the neck. She had been diagnosed with primary hyperparathyroidism from a fibula fracture and underwent parathyroidectomy at 13 years old. She had no family history of multiple endocrine neoplasia or jaw tumor syndrome. Genetic testing was not performed, and the histopathological diagnosis of the tumor had been parathyroid adenoma at the time. At 22 years old, she showed hypercalcemia after a femur fracture. Pulmonary metastases of parathyroid carcinoma in the bilateral lungs were found and surgically removed. Regarding the clinical course, her diagnosis was corrected from parathyroid adenoma to parathyroid carcinoma. At 33 years old, re-resection of the lung metastases was performed. For 10 years, her serum calcium level stayed within the normal range. However, her serum calcium level and intact parathyroid hormone eventually began to increase. Two masses suspected of being parathyroid carcinoma recurrence were found in the neck when she was 57 years old. En bloc resection was performed. Pathologically, the tumors were diagnosed as parathyroid adenoma. The serum calcium level and intact parathyroid hormone did not decrease after the operation. A 99mTc-methoxy-isobutyl-isonitrile- and 18F-fluorodeoxyglucose-negative, 11C-methionine-positive tumor was detected at the right side of the trachea in the neck. The tumor was removed, along with the thyroid, muscle, and trachea that were involved. The pathological diagnosis was parathyroid carcinoma recurrence. The serum calcium level and intact parathyroid hormone decreased temporarily but had increased again 8 months later. Methionine-positive tumors were found at the right side of the trachea and suspected of being a recurrence. Denosumab reduced her serum calcium level, and radiation successfully suppressed the growth of the recurrent tumors. We have reported a rare case of parathyroid carcinoma in a child who has survived for over 40 years. Positron emission tomography of 11C-methionine was useful for detecting local recurrence. This patient's long-term survival has been attributed to multimodality treatment including repeated surgery, medication, and radiation.


Functional expression of Rhizopus oryzae lipase in Pichia pastoris: high-level production and some properties.
The mature lipase of the fungus Rhizopus oryzae (ROL) was functionally expressed and secreted in the methylotrophic yeast Pichia pastoris. In a batch cultivation, where methanol feeding was linked to the dissolved oxygen content in the cultivation solution, a lipase activity of 500,000 units per liter (60 mg active lipase per liter) of culture was achieved after initial glycerol feeding of the culture. Recombinant ROL lipase was purified to homogeneity by a simple two-step purification procedure and had a specific activity of 8571 U mg-1 (triolein, 30 degrees C, pH 8.1) which is comparable with the purified native enzyme. The properties of the recombinant lipase were similar to those reported both for the native lipase and for the enzyme expressed in Escherichia coli and refolded from inactive inclusion bodies.


Ataxia.
The approach to the child with ataxia requires a detailed history and careful general and neurological examination as well as selected blood work and brain imaging and increasingly available genetic testing for inherited ataxias that usually have an episodic or progressive presentation. The differential of acute and recurring ataxia covered in this chapter includes intoxication (e.g., antiepileptics, lead, alcohol), postinfectious cerebellitis, hemorrhage, ischemic stroke, tumor (posterior fossa or cerebellum), brainstem encephalitis, occult neuroblastoma, Miller Fisher syndrome, conversion reaction, multiple sclerosis, epileptic pseudoataxia, vasculitis (e.g., Kawasaki), metabolic etiologies (e.g., maple syrup urine disease, pyruvate dehydrogenase deficiency, ornithine transcarbamylase deficiency, biotinidase deficiency, Hartnup disease, and argininosuccinic aciduria), migraine, migraine equivalents (benign paroxysmal positional vertigo), autosomal dominant episodic ataxias (with seven types currently identified), and hypothyroidism. Cooperation with therapists and providers from other specialties including ophthalmology and genetics and metabolism is essential to caring for these children and their families.


SARS-CoV-2 variant detection with ADSSpike.
The SARS-CoV-2 coronavirus pandemic has been an unprecedented challenge to global pandemic response and preparedness. With the continuous appearance of new SARS-CoV-2 variants, it is imperative to implement tools for genomic surveillance and diagnosis in order to decrease viral transmission and prevalence. The ADSSpike workflow was developed with the goal of identifying signature SNPs from the S gene associated with SARS-CoV-2 variants through amplicon deep sequencing. Seventy-two samples were sequenced, and 30 mutations were identified. Among those, signature SNPs were linked to 2 Zeta-VOI (P.2) samples and one to the Alpha-VOC (B.1.17). An average depth of 700 reads was found to properlycorrectly identify all SNPs and deletions pertinent to SARS-CoV-2 mutants. ADSSpike is the first workflow to provide a practical, cost-effective, and scalable solution to diagnose SARS-CoV-2 VOC/VOI in the clinical laboratory, adding a valuable tool to public health measures to fight the COVID-19 pandemic for approximately $41.85 USD/reaction.


Mitochondrial DNA damage is a hallmark of chemically induced and the R6/2 transgenic model of Huntington's disease.
Many forms of neurodegeneration are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage, however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are primary events in the delayed onset observed in Huntington's disease (HD). We hypothesize that an age-dependent increase in mtDNA damage contributes to mitochondrial dysfunction in HD. Two HD mouse models were studied, the 3-nitropropionic acid (3-NPA) chemically induced model and the HD transgenic mice of the R6/2 strain containing 115-150 CAG repeats in the huntingtin gene. The mitochondrial toxin 3-NPA inhibits complex II of the electron transport system and causes neurodegeneration that resembles HD in the striatum of human and experimental animals. We measured nuclear and mtDNA damage by quantitative PCR (QPCR) in striatum of 5- and 24-month-old untreated and 3-NPA treated C57BL/6 mice. Aging caused an increase in damage in both nuclear and mitochondrial genomes. 3-NPA induced 4-6 more damage in mtDNA than nuclear DNA in 5-month-old mice, and this damage was repaired by 48h in the mtDNA. In 24-month-old mice 3NPA caused equal amounts of nuclear and mitochondrial damage and this damage persistent in both genomes for 48h. QPCR analysis showed a progressive increase in the levels of mtDNA damage in the striatum and cerebral cortex of 7-12-week-old R6/2 mice. Striatum exhibited eight-fold more damage to the mtDNA compared with a nuclear gene. These data suggest that mtDNA damage is an early biomarker for HD-associated neurodegeneration and supports the hypothesis that mtDNA lesions may contribute to the pathogenesis observed in HD.


Effect of glyburide on beta cell responsiveness to glucose in non-insulin-dependent diabetes mellitus.
Since the introduction of glyburide in 1984, many studies have evaluated the effects of this oral hypoglycemic agent on beta cell function in patients with non-insulin-dependent diabetes mellitus. The early studies, which were performed in patients receiving concomitant insulin therapy, may have underestimated the true effect of glyburide on insulin secretion. The more recent studies demonstrate that both short- and long-term glyburide therapy increase C-peptide levels in diabetic as well as nondiabetic subjects and that the effects of glyburide are comparable to those of the other second-generation sulfonylurea, glipizide. The effects of glyburide on insulin secretory rates calculated from plasma C-peptide levels were recently evaluated using individually derived C-peptide kinetic parameters and a validated open two-compartment model of peripheral C-peptide kinetics. Glyburide did not influence fasting insulin secretion (196 +/- 34 versus 216 +/- 23 pmol/min) but did cause an increase in the total amount of insulin secreted over a 24-hour period (447 +/- 58 versus 561 +/- 55 nmol). This increase in the production of insulin was generated by an increase in amplitude of secretory pulses occurring after lunch and dinner rather than by a greater number of pulses. The full effect of glyburide on the beta cell became evident when glucose concentrations were clamped at the hyperglycemic level of 300 mg/dL both before and during treatment for a 3-hour period. During that time, insulin secretion rates increased by 221 percent in response to glyburide. Glyburide did not, however, completely reverse the beta cell secretory defect characteristic of non-insulin-dependent diabetes mellitus. In the patients receiving glyburide, the sluggish insulin secretory response to breakfast persisted, and the insulin secretory response during the hyperglycemic clamping was less than the response normally seen in nondiabetic subjects. These experiments suggest that the primary effect of glyburide on the beta cell is to increase its responsiveness to glucose. Although the precise mechanism of action of glyburide at the cellular level is unclear, in vitro studies suggest that its effect is mediated through binding with specific receptors on the beta cell membrane, which in turn leads to alterations in the cellular efflux of potassium ions and influx of calcium ions.


Studies on the binding of amylopectin sulfate with gastric mucin.
Amylopectin sulfate, a sulfated polysaccharide that has an antipeptic property, was examined for its ability to bind gastric mucins. After chemically cross-linking the amylopectin sulfate into an insoluble gel, its binding with mucins isolated from antral and fundic mucosa of canine stomachs was studied with chromatography. A component present in both mucin fractions bound to the amylopectin sulfate gel below pH 4.5. This binding was reversible, and the complex dissociated above pH 5. Similar binding properties were found with soluble amylopectin sulfate. The component of the mucine which bound to amylopectin sulfate differed from the one which did not bind in its electrophoretic mobility and in its higher proportion of basic amino acids and a lower hexosamine, serine, and threonine content. This study suggests that amylopectin sulfate may bind to gastric mucins only under conditions of low pH.


Cross-Sectional Analysis of Paronychias in the National Electronic Injury Surveillance System 1999-2018.
Paronychia is the most common hand infection. Prior paronychia studies were limited by small patient numbers. We conducted a national-level analysis over two decades, analyzing demographics, etiologies, and trends in paronychia cases. We conducted a retrospective analysis of paronychia cases in the 1999-2018 National Electronic Injury Surveillance System database. Sex, race, age, and cause were recorded and compared using χ2, ANOVA, and t tests. Multivariable linear regression analysis assessed changes in age, weight, and sex over time. We analyzed a total of 2,512 cases, with an average age of 27.6 ± 20.6 years, 45.5% females, and 25.6% white and 28.6% black patients. In multivariable linear regression, both age and weight significantly increased over time. Manicuring was the most common etiology (30.9%), increasing in incidence over time and with a higher frequency in adults (p < 0.0001) and females (p < 0.0001). There was a significant decrease in pediatric paronychia cases over time, particularly in 0- to 4-year-olds. Possible limitations include missed paronychia cases or additional non-paronychia cases due to improper coding, infrequent race reporting, and inability to analyze treatments or distinguish between paronychia subtypes. Paronychia cases were associated with increased age and weight over time with different presentations by age. Manicuring represents the largest growing paronychia etiology.


Managing medical emergencies in mental health settings using an interprofessional in-situ simulation training programme: A mixed methods evaluation study.
In the UK, people with severe mental illness die up to 20years earlier than the general population, prompting increased focus on physical health in mental illness. However, training for mental health inpatient staff to meet patients' physical health needs has not received the same attention, with physical health training often being reactive and lacking evidence of effectiveness. To evaluate an interprofessional, in situ, simulation training intervention for managing medical deterioration in mental health settings. Investigating the impact of training on: 1. Participants' knowledge, confidence, and attitudes towards managing medical deterioration; and 2. Incident reporting, as an objective index of incident management. Participants' perceptions of the impact on their practice were qualitatively explored. This evaluation employed a mixed-methods pre-post intervention design. Fifty-three healthcare professionals participated including: mental health nurses, psychiatrists, healthcare assistants, and activity co-ordinators from two busy psychiatric triage wards in South London, UK. The intervention comprised eight half-day sessions delivered weekly across two wards. Structured surveys assessed participants' knowledge, confidence, and attitudes towards medical deterioration pre and post training. Participants' experience of training was qualitatively captured through post-course surveys and focus groups three months post training. Incident reporting rates for seven-month periods pre and post training were compared. Following training, participants showed significant improvement in knowledge (p<0.001), confidence (p<0.001), and attitudes towards (p<0.02) managing medical deterioration. Incident reporting increased by 33% following training. Participants' reported improved confidence in managing medical deterioration, better understanding of effective communication, improved self-reflection and team working, and an increased sense of responsibility for patients' physical health. Interprofessional, in situ simulation training for medical deterioration yielded promising outcomes for individuals and teams. Simulation is an under-used training modality in mental health, offering a holistic training approach with the potential to provide educational and clinical benefits while supporting workforce resilience.


Plasmonic luminescent core-shell nanocomposites-enhanced chemiluminescence arising from the decomposition of peroxomonosulfite.
A core-shell structure of plasmonic luminescent nanocomposite, Ni@SiO2@FITC@SiO2 (NSFS) combining the stable luminescence of fluorophore with the excellent plasmonic property of metal nanomaterials, has been synthesized through layer-by-layer assembly. The effect of NSFS on the ultraweak chemiluminescence (CL) reaction of hydrogen peroxide (H2O2) and sodium bisulfite (NaHSO3) was explored for the first time. It was found that the CL intensity from the decomposition of peroxomonosulfite was significantly enhanced by NSFS. The mechanism of the nanocomposite-enhanced CL was revealed as the coupling of chemically induced excited states of fluorescein isothiocyanate (FITC) with surface plasmons of Ni nanoparticles based on studies of CL emission spectra, electron spin resonance spectra, extinction spectra and fluorescence spectra. The work sheds new light on the characteristics of the versatile materials and gives us new insight into the optical properties of fluorophores.


Ultrasound-Assisted Lipid Extraction from Chlorella sp.: Taguchi Design and Life Cycle Assessment.
The present study delved into the enhancement of essential oil (EO) extraction process from Chlorella sp. through the implementation of ultrasound-assisted extraction. The Taguchi method was instrumental in determining the ideal parameters for the extraction process, which encompassed ultrasonic amplitude, reaction duration, hexane/ethanol (HE/EtOH) ratio, and processing temperature. The empirical findings indicated that optimal EO yield was realized at an ultrasonic amplitude of 80%, a reaction timeframe of 15 min, a HE/EtOH proportion of 3:1, and a temperature setting of 40 °C. These optimal conditions were further substantiated through additional experimentation, resulting in an EO yield of 18.8 ± 0.2%. A fatty acid profile analysis disclosed that the extracted EO predominantly consisted of long-chain fatty acids (C14-C20), with Palmitic, Heptadecanoic, Oleic, and Linoleic acids featuring as the main components. Nevertheless, a high unsaturation rate of 37.9% in the EO could potentially render it vulnerable to oxidative deterioration during storage, consequently affecting the quality of the ensuing biodiesel. A life cycle assessment of the sonication technique utilized for biodiesel production from Chlorella sp. highlighted that lipid extraction was the principal contributor to global warming and ecotoxicity, as per the CML and TRACI methods. Hence, the ultrasound-assisted extraction of EO from Chlorella sp. appears to be a promising and ecologically viable substitute to conventional techniques employed for biodiesel production.


A simple clinical maneuver to reduce laparoscopy-induced shoulder pain: a randomized controlled trial.
To estimate the efficacy of a simple clinical maneuver that facilitates removal of residual abdominal carbon dioxide (CO2) after laparoscopic surgery to reduce shoulder pain. A total of 116 female outpatients who were scheduled for elective gynecologic laparoscopic surgery were randomly allocated to either the current standard (control group) or to additional efforts to remove residual CO2 at the end of surgery. In the control group, CO2 was removed by passive deflation of the abdominal cavity through the cannula. In the intervention group, CO2 was removed by means of Trendelenburg position (30 degrees) and a pulmonary recruitment maneuver consisting of five manual inflations of the lung. Postoperative shoulder pain was assessed before discharge and 12, 24, 36, and 48 hours later using a visual analog scale (VAS, 0-100). In addition, positional characteristics of the shoulder pain and incidence of postdischarge nausea and vomiting were recorded until 48 hours after discharge. Pain scores in the control and intervention groups were 30.3+/-4.5 compared with 15.6+/-3.0, 25.7+/-4.7 compared with 10.8+/-2.4, and 21.7+/-4.3 compared with 9.1+/-2.5 at 12, 24 and 36 hours after discharge, respectively (all P<.05). The intervention reduced positional pain from 63% to 31% (P<.05) and the incidence of postoperative nausea and vomiting from 56.5% to 20.4% (P<.001). This simple clinical maneuver at the end of surgery reduced shoulder pain as well as postoperative nausea and vomiting after laparoscopic surgery by more than half. www.clinicaltrials.gov, ClinicalTrials.gov, NCT00575237 I.


The maternal pheromone of the rat: testing some assumptions underlying a hypothesis.
Herein we report four experiments relating to the maternal pheromone of the rat that show (a) preweanling young consume pheromone-containing feces most conspicuously between 14 and 27 days; (b) they consume those feces preferentially; (c) such feces contain high levels of deoxycholic acid; and (d) preweanling young are deficient in deoxycholic acid. The data of these experiments lend support to the hypothesis that in responding to the pheromone the young ingest deoxycholic acid, a steroid believed to promote gut immunocompetence and brain myelination.


A plate holder for non-destructive testing of mesophase crystallization assays.
Here, we describe a goniometer holder to mount standard 96-well crystallization plates directly onto the goniometer head of an oscillation camera. This attachment was designed to check crystallization conditions straight from the crystallization plates under X-rays, and was proven to be useful for checking small crystals and solutions that destabilize monoolein-based lipidic cubic phase (LCP) crystallization experiments. A quick procedure for setting up LCP assays employing commercially available instruments is also reported.


Exercise and Neuropathy: Systematic Review with Meta-Analysis.
Peripheral neuropathies are a prevalent, heterogeneous group of diseases of the peripheral nervous system. Symptoms are often debilitating, difficult to treat, and usually become chronic. Not only do they diminish patients' quality of life, but they can also affect medical therapy and lead to complications. To date, for most conditions there are no evidence-based causal treatment options available. Research has increased considerably since the last review in 2014 regarding the therapeutic potential of exercise interventions for patients with polyneuropathy. Our objective in this systematic review with meta-analysis was to analyze exercise interventions for neuropathic patients in order to update a systematic review from 2014 and to evaluate the potential benefits of exercise on neuropathies of different origin that can then be translated into practice. Two independent reviewers performed a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria according to the PICOS approach were: neuropathic patients, exercise interventions only, an inactive or non-exercising control group, and solely randomized controlled trials with the following outcome parameters: neuropathic symptoms, balance parameters, functional mobility, gait, health-related quality of life, and HbA1c (glycated hemoglobin). A total of 41 randomized, controlled trials met all inclusion criteria, 20 of which could be included in the quantitative analysis. Study quality varied from moderate to high. Current data further support the hypothesis that exercise is beneficial for neuropathic patients. This is best documented for patients with diabetic peripheral neuropathy (DPN) (27 studies) as well as for chemotherapy-induced peripheral neuropathy (CIPN) (nine studies), while there are only few studies (five) on all other causes of neuropathy. We found standardized mean differences in favor of the exercise group of 0.27-2.00 for static balance, Berg Balance Scale, Timed-up-and-go-test, nerve conduction velocity of peroneal and sural nerve as well as for HbA1c in patients with DPN, and standardized mean differences of 0.43-0.75 for static balance, quality of life, and neuropathy-induced symptoms in patients with CIPN. For DPN, evidence-based recommendations can now be made, suggesting a combination of endurance and sensorimotor training to be most beneficial. For patients with CIPN, sensorimotor training remains the most crucial component. For all other neuropathies, more high-quality research is needed to derive evidence-based recommendations. Overall, it seems that sensorimotor training has great potential to target most neuropathies and combined with endurance training is therefore currently the best treatment option for neuropathies. (PROSPERO 2019 CRD42019124583)/16.04.2019.


StructAlign, a Program for Alignment of Structures of DNA-Protein Complexes.
Comparative analysis of structures of complexes of homologous proteins with DNA is important in the analysis of DNA-protein recognition. Alignment is a necessary stage of the analysis. An alignment is a matching of amino acid residues and nucleotides of one complex to residues and nucleotides of the other. Currently, there are no programs available for aligning structures of DNA-protein complexes. We present the program StructAlign, which should fill this gap. The program inputs a pair of complexes of DNA double helix with proteins and outputs an alignment of DNA chains corresponding to the best spatial fit of the protein chains.


Shape control of mesoporous silica nanomaterials templated with dual cationic surfactants and their antibacterial activities.
Mesoporous silica nanomaterials of different shapes (film, platelet, sphere, rod) were synthesized simply by tuning the mole ratio of dual cationic surfactant templates, cetyltrimethylammonium bromide (CTAB) and tetrabutylammonium iodine (TBAI). The film showed the most potent antibacterial activity against mycobacteria.


Ultrastructural features of a brain injury model in cat. I. Vascular and neuroglial changes and the prevention of astroglial swelling by a fluorenyl (aryloxy) alkanoic acid derivative (L-644,711).
We present qualitative and quantitative ultrastructural observations on the changes induced in neuroglia and blood vessels of gray matter of cat brain by an experimental acceleration-deceleration injury which, when used alone, causes negligible morbidity and mortality, but, when combined with systemic hypoxia, leads to coma and delayed death in approximately 50% of experimental subjects. An increase in the proportion of neuropil occupied by astrocytic cytoplasm is detectable qualitatively in layer Vb of pericruciate cortex 20 min after injury without hypoxia, and is maximal (22%, as measured morphometrically, vs 11.4% in controls) 40 min afterward. Near-normal values (14.1%) are obtained 100 min following the insult. If trauma is succeeded 40 min later by a 60-min period of hypoxia, there is prolongation of astrocytic edema and other neuroglial accompaniments of the traumatic lesion, such as aggregation of nuclear nucleoprotein granules and, in astrocytes, fusion of rosette ribosomes and enlargement of mitochondria. A decrease in luminal area occurs in capillaries 40 min after trauma applied alone. Hypoxia without trauma leads to a significant increase in capillary luminal area, which, however, is abolished when trauma precedes the hypoxic interlude. Intravenous injection of a non-diuretic, fluorenyl derivative (L-644,711) of (aryloxy)alkanoic acid loop diuretics, completely prevents the astrocytic swelling ordinarily present 40 min after acceleration-deceleration injury. Also, L-644,711 improves mortality and morbidity scores in cats subjected to trauma with hypoxia. We suggest that astroglial swelling may be a critical step in the evolving pathology of this head injury model and its prevention, as by L-644,711 administration, may have relevance to the treatment of cerebral edema in human head injury and other clinical disorders accompanied by astrocytic swelling.


Sex- and age-related variations in the in vitro heparin-releasable lipoprotein lipase from mononuclear leukocytes in blood.
An in vitro heparin release of lipoprotein lipase (LPL) from whole blood, mainly from monocytes, was demonstrated by (1) the time-course of lipolytic activity with the presence of 10 U/ml heparin at 37 degrees C, (2) the distribution of LPL activity in monocyte and lymphocyte fractions, (3) an immuno-inactivation with anti-LPL immunoglobulin (IgG) and (4) responses to various compounds such as NaCl, protamine sulfate, heparin, and serum activator. The in vitro heparin-releasable LPL activity from blood correlated well with the LPL activity of postheparin plasma obtained from both normolipidemic and hyperlipidemic rabbits. Studies in humans revealed sex- and age-related variations in the in vitro heparin-releasable LPL from monocytes in the blood of 134 normal subjects and 24 hypertriglyceridemic subjects: The mean LPL activity was significantly higher in normal females over the age of 30, than in the corresponding males. In the hypertriglyceridemic group, the LPL activity was also higher in females than in males, but it was not significant. The in vitro heparin-releasable LPL activity from monocytes in blood was comparable to the LPL activity derived from adipose tissue and postheparin plasma, and thus it reflects lipoprotein metabolism.


Effects of renal autotransplantation on ureteral peristalsis.
The ureteral peristalsis following autotransplantation is being investigated. It seems surprising that denervation does not cause more detectable changes in peristaltic pattern.


CYP450 polymorphisms and clinical pharmacogenetics of ibuprofen after lower third molar extraction.
This study hypothesized that drugs accumulate in the bloodstream of poor-metabolizing patients and may have more adverse effects and different pain perceptions and aimed to investigate the influence of CYP450 polymorphisms on acute postoperative pain, swelling, and trismus controlled by ibuprofen (600 mg) in 200 volunteers after dental extraction. In addition, surgical outcomes can determine pain, edema, and trismus and indicate inflammatory reactions after oral surgeries. Genetic sequencing was performed to identify CYP450 polymorphisms and the surgical parameters evaluated: pre and postoperative swelling, trismus, and temperature; self-reported postoperative pain with visual analog scale (VAS); rescue medication consumed; and severity of adverse reactions. A multiple linear regression model with independent variables [single nucleotide polymorphisms (SNPs), BMI (body mass index), duration, and difficulty of surgery] and dependent variables [postoperative pain by sum of pain intensity difference (SPID), trismus, and swelling] was used for analysis. The duration of surgery was a predictor for pain at 8 h and 96 h after surgery, and BMI was a predictor for both swelling and trismus on the 2nd postoperative day. When evaluating CYP2C8 and C9 genotyped SNPs, it was observed that normal metabolizers showed higher pain levels than the intermediate/poor metabolizers on the postoperative periods as compared with time 0 h. In another analysis, the poor metabolizers for CYP2C8 and C9 presented lower levels of postoperative pain after 8 h and used rescue medication earlier than normal metabolizers. Ibuprofen 600 mg was very effective in controlling inflammatory pain after lower third molar surgeries, without relevant adverse reactions; although in a very subtle way, patients with poor metabolism had higher levels of pain in the first hours, and no longer after 8 h, and used pain relief medication earlier. The study was registered with ClinicalTrials.gov ID (NCT03169127), on March 16th, 2017.


Adolescents' and young adults' experiences of childhood cancer: descriptions of daily life 5 years after diagnosis.
Survivors of childhood cancer are a growing population in society. These young people have a high risk of developing chronic health problems with a potential strong impact on their lives. How a childhood cancer experience affects survivors in adolescence has been studied to a limited extent; an increased understanding of this young group is needed to improve follow-up care. The aim of this study was to gain a deeper understanding of how childhood cancer affects the lives of survivors by exploring adolescents' and young adults' views of what it is like living with this experience. Fifty-nine 11- to 22-year-olds were interviewed a median of 5 years after a cancer diagnosis (response rate, 66%). Data were collected through telephone interviews and were analyzed using qualitative content analysis techniques. Three groups of informants were identified according to their descriptions of the influence of cancer treatment on their daily life: "feeling like anyone else" (informants who described that the cancer experience had almost no influence on current life) (49%), "feeling almost like others" (those who described some influence) (44%), and "feeling different" (those describing a great influence on current life) (7%). Most of the adolescents and young adults appear to get along well, although many informants described that life was affected to some extent by having had cancer. Follow-up care is needed that can identify those young survivors of childhood cancer having trouble with daily life and offer them support to strengthen their resources in managing difficulties in relation to having had cancer.


Vaginal microbiota signatures in healthy and purulent vulvar discharge sows.
Purulent vulvar discharges, primarily caused by genito-urinary tract infections, are an important source of economic loss for swine producers due to sow culling and mortality. However, the agents that compose the vaginal microbiota of sows and their changes during infections are not well understood. The first goal of this study was to characterize and compare the vaginal bacterial content of healthy (HE, n = 40) and purulent vulvar discharge sows (VD, n = 270) by a culture-dependent method and MALDI-TOF MS identification. Secondly, we performed 16S rRNA targeted metagenomic approach (n = 72) to compare the vaginal microbiota between these groups. We found a wide variety of bacteria, with Proteobacteria, Firmicutes, and Bacteroidota being the most abundant phyla in both groups, as well as Escherichia-Shigella, Streptococcus, and Bacteroides at the genus level. Most agents identified in the sequencing method also grew in the culture-dependent method, showing the viability of these bacteria. Alpha diversity did not differ between HE and VD sows, regarding sample richness and diversity, but a beta-diversity index showed a different microbiota composition between these groups in two tested herds. ANCOM analysis revealed that Bacteroides pyogenes were more abundant in VD females and can be a marker for this group. Other agents also require attention, such as the Streptococcus dysgalactiae and Staphylococcus hyicus found in remarkably greater relative abundance in VD sows. Network analysis revealed important positive correlations between some potentially pathogenic genera, such as between Escherichia-Shigella, Trueperella, Streptococcus, Corynebacterium, and Prevotella, which did not occur in healthy sows. We conclude that the alteration of the vaginal microbiota between healthy and purulent vulvar discharge sows, although not extreme, could be due to the increase in the relative abundance of specific agents and to associations between potentially pathogenic bacteria.


Complementary chimeric isoforms reveal Dscam1 binding specificity in vivo.
Dscam1 potentially encodes 19,008 ectodomains of a cell recognition molecule of the immunoglobulin (Ig) superfamily through alternative splicing. Each ectodomain, comprising a unique combination of three variable (Ig) domains, exhibits isoform-specific homophilic binding in vitro. Although we have proposed that the ability of Dscam1 isoforms to distinguish between one another is crucial for neural circuit assembly, via a process called self-avoidance, whether recognition specificity is essential in vivo has not been addressed. Here we tackle this issue by assessing the function of Dscam1 isoforms with altered binding specificities. We generated pairs of chimeric isoforms that bind to each other (heterophilic) but not to themselves (homophilic). These isoforms failed to support self-avoidance or did so poorly. By contrast, coexpression of complementary isoforms within the same neuron restored self-avoidance. These data establish that recognition between Dscam1 isoforms on neurites of the same cell provides the molecular basis for self-avoidance.


RADIOIODINE THERAPY FOR DIFFERENTIATED THYROID CARCINOMA : INHS ASVINI EXPERIENCE.
During last 17 years, 175 patients of carcinoma thyroid were treated in this centre. Hundred patients (57%) of papillary carcinoma formed majority. Fifty four patients (31%) were follicular carcinoma and 15 (8.5%) were mixed variety. Two (1.3%) were medullary carcinoma, 3 (1.7%) anaplastic type and 1 (0.5%) hurthle cell carcinoma. After surgery these patients were assessed for radio iodine uptake, residual thyroid tissue and distant metastasis which determined the dose of radioiodine for ablation. Fifty two per cent (91) patients presented as multi nodular goitre, 22.3 per cent (39) as solitary nodule, 13.7 per cent (24) had lymph node metastasis, 5.7 per cent (10) bone metastasis, 2.5 per cent (4) had lung metastasis and 3.8 per cent (7) presented as thyrotoxicosis. Average number of therapy for complete ablation in papillary carcinoma was 1.5, follicular 1.78 and mixed variety 1.5. 72.6 per cent cases (127) needed single dose for ablation, 14.9 per cent (26) needed 2 doses and 5.7 per cent (10) required 3 doses. Only 6.8 per cent (12) cases needed 4 to 8 doses. Average dose of I-131 administered for ablation was 157 mci in males and 124 mci in females of papillary carcinoma thyroid. Males in follicular variety required 204 mci and females needed only 120 mci. In mixed variety males required 177 mci and females required 62.5 mci for complete ablation. 144 patients (82.3%) were followed up to 5 years and remaining patients from 6 to 17 years. These patients are followed up once in a year or alternate years. Follow-up and medical record keeping for defence personnel is done with meticulous care, therefore followup results are very encouraging.


Campylobacter enteritis and bloody stools in the neonate.
Within 72 hours of birth three babies had loose stools containing fresh blood, mucus, and Campylobacter jejuni/coli. Campylobacter enteritis should be considered in newborn babies passing blood per rectum.


Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of sympathetic nervous system.
The relationship between interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. We found in the present study that intrathecal (i.t.) injection of IL-1β increased pain behavior. In addition, i.t. IL-1β injection caused an elevation of the blood glucose level. The time-course study showed that maximal blood glucose level was observed 30 and 60 min after i.t. IL-1β administration. Furthermore, i.t. injection of IL-1β enhanced the blood glucose level when mice were orally fed with d-glucose. The i.t. administration of IL-1β antagonist (AF12198) inhibited the hyperglycemia and pain behaviors induced by IL-1β. We found in the present study that adrenal tyrosine hydroxylase (TH) mRNA level was also increased by i.t. IL-1β injection. Furthermore, intraperitoneal (i.p.) pretreatment with phentolamine (an α(1)-adrenergic blocker) or yohimbine (an α(2)-adrenergic blocker) significantly attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. However, the blood glucose level and pain behavior were not affected by butoxamine (a β(2)-adrenergic blocker), whereas metoprolol (a β(2)-adrenergic blocker) enhanced IL-1β-induced blood glucose level and pain behavior in mice fed with d-glucose. However, its effect was not statistically significant. Our results suggest that IL-1β administered i.t. increases the blood glucose level via an activation of α adrenergic nervous system.


Placobdelloides sirikanchanae sp. nov., a new species of glossiphoniid leech and a parasite of turtles from lower southern Thailand (Hirudinea, Rhynchobdellida).
Abstract A new species of glossiphoniid leech, Placobdelloides sirikanchanae sp. nov., is reported in the Asian leaf turtle (Cyclemys dentata) and the dark-bellied leaf turtle (C. enigmatica) from Songkhla Province, southern Thailand. The examination of morphological characters revealed that this new species is similar to P. siamensis (Oka, 1917), a common turtle leech species found in Thailand. Placobdelloides sirikanchanae sp. nov. demonstrates distinct morphological characters, with an elongated, narrow body, 13-17 well-developed knob papillae on each annulus, dark brown to greenish dorsal color with a crimson median line, the absence of a scarlet dot, different male and female gonopore distributions, a rough posterior sucker with a random pit distribution, and 104-115 eggs per clutch. The phylogenetic relationships of COI-ND1 genes were clarified and shown to be distinct from those of P. siamensis. Additionally, habitat preferences tended toward low oxygen conditions such as puddles or water patches on rubber plantations.


Toxic metal (Cd, Hg, Mn, Pb) partition in the maternal/foetal unit: A systematic mini - review of recent epidemiological studies.
The aim of this study was to summarise the available information regarding the partition of toxic metal (Cd, Hg, Mn, Pb) levels in the maternal/foetal unit from large epidemiological studies. We performed a systematic search of PubMed/MedLine, EMBASE, and ISI Web of Science for papers on Cd, total Hg, Mn or Pb levels in the maternal/cord blood that were published in English (n > = 200; 2010-2017). Data on year of publication, sample size, location, year of survey, and main results were extracted. We found a total of 35 papers. Most studies included large convenience samples of healthy pregnant women. The maternal/cord blood was properly used as a biomarker of prenatal exposure to toxic metals. The partition of these toxic metal levels in the maternal/foetal unit was metal-specific. Cd median levels (IQR) in cord blood reported worldwide were much lower [∼ 70 % < LOD = ± 0.11 μg/L] than those found in maternal blood [0.23 μg/L (0.15-0.35), ∼ 65 % > LOD]. Considering that Cd was under LOD in 70 % of the cord blood, Cd cord:maternal ratio as well as Cd cord proportion were not provided. Total Hg median levels (IQR) in cord blood [0.75 μg/L (0.40-1.19), ∼30 % < LOD = ±0.35 μg/L] were usually higher than in maternal blood [0.55 μg/L (0.40-0.85), ∼ 10 % < LOD = ±0.15 μg/L]. Hg cord:maternal ratio was 1.34 (1.00-1.91), and infants born would have Hg cord:(cord + maternal) proportion ranged from 0.50 to 0.63. Mn was the only metal that was detected in 100 % in both maternal (LOD : ±0.50 μg/L) and cord (LOD = ±0.2 μg/L) blood. Mn median levels (IQR) in cord blood [32.96 μg/L (26.90-40.10)] were 2 times higher than in maternal blood [14.01 μg/L (11.50-17.58)]. Mn cord:maternal ratio was 2.35 (1.09-3.80), and infants born would have Mn proportion ranged from 0.52 to 0.79. Pb median levels (IQR) in cord blood [5.79 μg/L (4.34-8.38), ∼ 5% < LOD : ±2.07 μg/L] were usually equal to or lower than those reported in maternal blood [8.07 μg/L (5.79-10.76), ∼ 1% < LOD = ±1.03 μg/L]. Pb cord:maternal ratio was 0.71 (0.59-0.96), and infants born would have Pb proportion ranged from 0.37 to 0.49. Globally, the results indicate that total Hg and Mn levels were lower in maternal blood but higher in cord blood. However, much greater variability was seen with Cd and Pb. At delivery, total Hg and Pb levels in maternal blood were strong predictors of cord blood levels. Our findings empty that understanding the partition, levels and correlations of toxic metals in the maternal/cord blood may help to elucidate the adverse effects of these metals on foetuses and neonates.


Transferrin-derived synthetic peptide induces highly conserved pro-inflammatory responses of macrophages.
We examined the induction of macrophage pro-inflammatory responses by transferrin-derived synthetic peptide originally identified following digestion of transferrin from different species (murine, bovine, human N-lobe and goldfish) using elastase. The mass spectrometry analysis of elastase-digested murine transferrin identified a 31 amino acid peptide located in the N2 sub-domain of the transferrin N-lobe, that we named TMAP. TMAP was synthetically produced and shown to induce a number of pro-inflammatory genes by quantitative PCR. TMAP induced chemotaxis, a potent nitric oxide response, and TNF-alpha secretion in different macrophage populations; P338D1 macrophage-like cells, mouse peritoneal macrophages, mouse bone marrow-derived macrophages (BMDM) and goldfish macrophages. The treatment of BMDM cultures with TMAP stimulated the production of nine cytokines and chemokines (IL-6, MCP-5, MIP-1 alpha, MIP-1 gamma, MIP-2, GCSF, KC, VEGF, and RANTES) that was measured using cytokine antibody array and confirmed by Western blot. Our results indicate that transferrin-derived peptide, TMAP, is an immunomodulating molecule capable of inducing pro-inflammatory responses in lower and higher vertebrates.


Responses of human sensory characteristics to 532 nm pulse laser stimuli.
Lasers are advantageous in some applications to stimulate a small target area and is used in various fields such as optogenetic, photoimmunological and neurophysiological studies. This study aims to implement a non-contact sense of touch without damaging biological tissues using laser. Various laser parameters were utilized in safety range to induce a sense of touch and investigate the human responses. With heat distribution simulation, the amount of changes in the temperature and the tendency in laser parameters of sensory stimulation were analyzed. The results showed the identified tactile responses in safety range with various laser parameters and temperature distribution for the laser stimulus was obtained through the simulation. This study can be applied to the areas of sensory receptor stimulation, neurophysiology and clinical medicine.


Effect of colestimide on the concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dizenzofurans, and polychlorinated biphenyls in blood of Yusho patients.
Oral colestimide was reported to lower the concentration of PCDDs, PCDFs, and PCB in the blood of humans. A pilot study showed that the arithmetic mean total TEQ concentrations of PCDDs, PCDFs, and PCBs in the blood of subjects after the trial decreased approximately 20 % compared to pre-trial levels, suggesting that colestimide could decrease human dioxin levels. We designed the current clinical trial study based on this information. In this study, we examined whether colestimide could reduce the individual congener concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients. Out of the 36 Yusho patients who participated in the clinical trial, 26 patients self-administered colestimide 3 g/day orally for 6 months. The concentrations of PCDDs, PCDFs and PCBs in the blood of 26 Yusho patients before the trial were compared with those after the trial. The arithmetic mean total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of the 26 Yusho patients before and after the clinical trial were 42-303 (mean: 130, median: 120) and 43-283 (mean: 132, median: 118) pg TEQ/g lipid, respectively. The sums of the concentrations of 58 PCB congeners measured in the blood of Yusho patients before and after the trial were 321-2643 (mean: 957, median: 872) and 286-2007 (mean: 975, median: 806) ng/g lipid, respectively, indicating that the concentrations of PCDDs, PCDFs, and PCBs after the trial were almost the same as those before the trial. Among congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs, most congeners of these compounds did not show a statistically significant decrease after the trial. Colestimide may not be beneficial in reducing the high blood levels of dioxin-like compounds in Yusho patients.


Uptake of [3H]serotonin in the abdominal ganglion of Aplysia californica. Further studies on the morphological and biochemical basis of presynaptic facilitation.
Sensitization of the gill-withdrawal reflex in Aplysia california is mediated, in part, by a group of identified neurons, the L29 cells, which produce presynaptic facilitation of transmitter release from siphon sensory neurons. Physiological and pharmacological studies have provided indirect evidence that the L29 cells are serotonergic. In the present study we have used the specific uptake [3H]serotonin ([3H]5-HT) and electron-microscopic autoradiography in combination with horseradish peroxidase-labeling of identified neurons to characterize the fine structure of Aplysia serotonergic terminals and to examine more directly the transmitter biochemistry of the L29 neurons. Abdominal ganglia were incubated for 2 h in 10(-6) M [3H]5-HT and thick and thin plastic sections examined with the light and electron microscope. L29 varicosities, identified by labeling with HRP, were found to accumulate [3H]5-HT. In addition, [3H]-5-HT was localized to unidentified varicosities within the neuropil as well as to vesicle-filled terminals that formed axosomatic contacts in the cortical regions of the ganglion. The processes that accumulated [3H]5-HT contained conspicuous dense core vesicles identical in morphology to those previously described for L29. Some processes were found to make contact with HRP-labeled varicosities of sensory neurons. Comparison with results obtained from ganglia exposed to [3H]5-HT in the presence of either non-radioactive 5-HT or non-radioactive dopamine indicate that the uptake process is transmitter-specific. These studies provide additional evidence that the L29 cells are serotonergic and are consistent with the notion that aminergic neurons may be preferentially involved in modulatory synaptic actions.


Methods for preliminary determination of pemetrexed in macromolecular drug-carrier systems.
Pemetrexed (PMX) is an antifolate drug utilized in the treatment of non-small cell lung cancer. For studies of potential macromolecular carriers for PMX, fast and precise methods were developed to determine the bound and free drug contained in investigated conjugate preparations. The analysis of the total amount of PMX in conjugates was based on absorption spectrophotometry. The linearity was found in the range of 4.697-46.97 μmol L(-1) PMX. The limit of quantitation was 1.070 μmol L(-1). The method for the analysis of unbound PMX was based on size-exclusion chromatography and detection at 225 nm. This method shows linear range of 2.230-223.0 μmol L(-1). LOQ was 0.539 μmol L(-1). The proposed methods can be used both for the characterization of the polysaccharide based conjugates of PMX and for the determination of conjugate drug release profiles.


Association of residual inflammatory risk with stroke recurrence in patients with acute ischaemic stroke or transient ischaemic attack.
The aim was to explore the association of residual inflammatory risk (RIR) with stroke recurrence after an index acute ischaemic stroke or transient ischaemic attack. This study was based on the Third China National Stroke Registry. A total of 5840 patients with two high sensitivity C-reactive protein (hsCRP) measurements at baseline and at 3 months were included in the analysis. High RIR was defined as an hsCRP ≥3 mg/l. Patients were divided into four groups: persistent high RIR (first high then high hsCRP), attenuated RIR (first high then low hsCRP), increased RIR (first low then high hsCRP) and persistent low RIR (first low then low hsCRP). The primary outcome was new stroke onset during the 1-year follow-up. Secondary outcomes included composite vascular events, all-cause mortality and poor functional outcome (modified Rankin Scale score 3-6). During the 1-year follow-up, 523 (9.0%) patients had stroke recurrence. Patients with persistent high RIR had an increased risk of stroke recurrence (hazard ratio with 95% confidence interval 1.39, 1.08-1.78), compared with those with persistent low RIR. Similar results were found for the outcome of composite vascular events, mortality and poor functional outcome. An increased risk of stroke recurrence was further found in patients with persistent high RIR and intracranial artery stenosis or large-artery atherosclerosis stroke subtype. In patients with acute ischaemic stroke or transient ischaemic attack, persistent high RIR increased the risks of 1-year stroke recurrence, especially in those with intracranial artery stenosis or large-artery atherosclerosis subtype, composite vascular events, mortality and poor functional outcome.


Dynamic Change of Sedimental Microbial Community During Black Bloom-an In Situ Enclosure Simulation Study.
Black bloom is a worldwide environmental problem. Sediment microbes play important roles in the process of black bloom. The dynamic change of sedimental microbial community and their potential link between taste and odor compounds during black bloom was investigated in an in situ black bloom enclosure simulation experiment. Through high-throughput sequencing and analysis, pronounced shifts of sedimental microbial community were observed on the 3rd and 7th day in the black bloom group. Microbes in Cyanobacteria, Verrucomicrobia, Planctomycetes, and Actinobacteria were obviously increased, while microbes from the phyla OP8, Chloroflexi, and Acidobacteria were decreased significantly. RDA analysis revealed that the concentrations of chlorophyll a (Chla), total phosphorus (TP), and turbidity (NTU) in the water and the TP, TN concentrations in the sediment were the main environmental factors that affect the microbial community in the sediment. Correlation analysis revealed that microbes Dechloromonas sp. (OTU003567 and OTU000093), Desulfococcus sp. (OTU000911), Chromatiaceae (OTU001222), and Methanosaeta sp. (OTU004809) were positively correlated with the taste and odor substances in the sediment, such as dimethyl sulfide (DMS), β-ionone, β-cyclocitral and geosmin. The sedimental microbial community gradually recovered in the late phase of black bloom, indicating the stability and self-recovery ability of the sedimental microbial community during black bloom. Noteworthily, we observed many possible pathogens increased significantly during the black bloom, which alerts us to keep away from contaminated sediment when black bloom occurred.


[Iodine concentration in cooking salt consumed in Lubumbashi and the iodine status of vulnerable people: case study of pregnant women living in underprivileged areas].
Consumption of low iodine salt can cause different types of disorders associated with iodine deficiency. This study aims to determine iodine content in table salt consumed in Lubumbashi and iodine status of pregnant women who are the main target of iodine deficiency. aAdescriptive cross-sectional study was devoted to an iodometric iodine analysis of 739 salt samples collected from the households and the markets of Lubumbashi in 2014. Previously, urinary iodine concentrations were determined in 225 pregnant women received for consultation from 15 March 2009 to 25 April 2011 by mineralization technique using ammonium persulphate. Our survey found that 47.5% of the cooking salt samples were adequately iodized (from 15 to 40 ppm), 36,9% of the samples had low iodine levels, 7,4% of the samples had too much iodine and 8,1% of the samples were not iodized. Iodine concentration in the analyzed cooking salt reached an overall average of 54,9%, being clearly below the WHO Standards (90%). By measuring urinary iodine concentration of pregnant women, iodine deficiency (urinary iodine <150 µg/l) was observed in 52%. The low availability of iodine from consumed salt in Lubumbashi could be responsible for a large proportion of the observed iodine deficiency in pregnant women, exposing them to the major risks for disorders associated with iodine deficiency.


A small number of residual teeth after the mandibular resection of oral cancer is associated with titanium reconstruction plate exposure.
Reconstruction plates are used to treat patients with a segmental mandibular defect after oral cancer surgery. Reconstruction plate failure analysis has rarely focused on occlusion, which conducts a mechanical force to the mandible and the plate. To determine the prognostic factors, we retrospectively evaluated patients who underwent reconstruction of a mandibular segmental defect with a reconstruction plate and assessed the number of residual paired teeth. From among 390 patients with oral cancer who visited University of Tsukuba Hospital (Tsukuba, Japan) between 2007 and 2017, we selected and analyzed the data of 37 patients who underwent segmental resection of the mandible and reconstruction with reconstruction plates. Prognostic factors evaluated were patient age, sex, TNM classification, plate manufacturer, treatment with radiotherapy or chemotherapy, whether the patient had diabetes or smoked, and whether the patient had a small number of residual paired teeth, plate length, and use of a fibular-free flap. Among these 37 patients, eight reconstruction plates had intraoral or extraoral exposure and were removed in 5 years. Kaplan-Meier and log-rank analyses revealed that the prognosis for the 5-year plate exposure-free rate was significantly poorer for patients with a small number of residual teeth than for patients with no teeth or those with a large number of residual teeth (.01). Univariate Cox regression analysis revealed that a small number of residual teeth was a significant prognostic factor in the loss of a reconstruction plate (hazard ratio: 5.63; 95% confidence interval [1.10, 25.85]; .04). A small number of residual teeth after the segmental resection of oral cancer is significantly involved in reconstruction plate survival and may be important in predicting reconstruction plate prognosis.


NeuroD1 Dictates Tumor Cell Differentiation in Medulloblastoma.
Tumor cells are characterized by unlimited proliferation and perturbed differentiation. Using single-cell RNA sequencing, we demonstrate that tumor cells in medulloblastoma (MB) retain their capacity to differentiate in a similar way as their normal originating cells, cerebellar granule neuron precursors. Once they differentiate, MB cells permanently lose their proliferative capacity and tumorigenic potential. Differentiated MB cells highly express NeuroD1, a helix-loop-helix transcription factor, and forced expression of NeuroD1 promotes the differentiation of MB cells. The expression of NeuroD1 in bulk MB cells is repressed by trimethylation of histone 3 lysine-27 (H3K27me3). Inhibition of the histone lysine methyltransferase EZH2 prevents H3K27 trimethylation, resulting in increased NeuroD1 expression and enhanced differentiation in MB cells, which consequently reduces tumor growth. These studies reveal the mechanisms underlying MB cell differentiation and provide rationales to treat MB (potentially other malignancies) by stimulating tumor cell differentiation.


Catecholaminergic activity in idiopathic torsion dystonia.
Day and nighttime melatonin and dopamine-beta-hydroxylase activity were measured in blood from 10 Jewish and 9 non-Jewish dystonics and from 22 nondystonic family members. Groups did not significantly differ on either of these measures. These results do not support a generalized abnormality of noradrenergic release in dystonia.


Low-dose Aspirin may Prevent Preeclampsia by Inhibiting the Expression of ATF2.
To explore the ATF2 expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients. Preeclampsia is a severe pregnancy-related hypertension disorder and refers to hypertension. This study was designed to explore the activating transcription factor 2 (ATF2) expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients. Firstly, we collected the plasma of normal and preeclampsia pregnancies and quantified the expressions of ATF2 by ELISA. Then we quantified the expression of the three downstream target genes of ATF2 (IL-8, IL-6 and MMP-2). Finally, we collected and quantified the interventional and observational group plasma. All data were compared by t-test (p<0.05). ATF2 and its target genes (IL-6, IL-8 and MMP-2) were upregulated in preeclampsia patients. In addition, ATF2 and its target genes were downregulated in the interventional group (LDA-treated group). Our results indicated that LDA could inhibit ATF2 expression in preeclampsia. It suggests that ATF2 may be a potential target of LDA in the prevention of preeclampsia.


O2-chemoreflex drive of ventilation in awake birds at rest.
Three varieties of birds (a non-flyer, the chicken; a diver, the duck; a flyer, the pigeon) were studied in resting conditions at neutral ambient temperature, while awake, either intact or sham operated, or after bilateral chronic carotid body denervation. Tidal volume (VT), ventilatory period (T) and minute volume (V = VT/T) measured plethysmographically, were recorded breath-by-breath in steady state at two levels of oxygenation, and in the course of transient pure O2 inhalation (60-sec O2-test). O2 partial pressures in the inspired and expired gases (PIO2 and PETO2), and in the arterial blood (PaO2) were also measured. In intact and sham operated birds, the abrupt switch from a normoxic gas mixture (FIO2 = 0.21) to pure O2 resulted shortly in rapid increases of PIO2, PETO2 and paO2, and in a fall of V which was completed within 20--30 sec and accounted for about 30% of the control minute volume. In the animals previously made hypoxic (FIO2 = 0.12) and hyperventilating, the O2-test provoked a 50--60% fall of V. In chickens, a decreased VT and an increased T contributed to the transient ventilatory changes; in ducks, mainly VT changed, and in the pigeon only T changed. In the birds with denervated carotid bodies, there were no ventilatory responses to hypoxia and to the O2-test. A few of these birds developed a tachypneic response to hypoxia with no apparent change in the effective pulmonary ventilation, which was partly overcome during the O2-test. It is concluded that in the three varieties of birds, the O2-chemoreflex drive from the carotid bodies controlled about 30% of the resting minute volume near sea level, and 50--60% in hypoxic conditions duplicating an altitude exposure to 4000 m.


An iterative requirements specification procedure for decision support systems.
Requirements specification is a key element in a DSS development project because it not only determines what is to be done, it also drives the evolution process. A procedure for requirements elicitation is described that is based on the decomposition of the DSS design task into a number of functions, subfunctions, and operators. It is postulated that the procedure facilitates the building of a DSS that is complete and integrates MIS, modelling and expert system components. Some examples given are drawn from the health administration field.


Temporal decrease of trivalent chromium concentration in a standardized algal culture medium: experimental results and implications for toxicity evaluation.
The fate of two trivalent chromium salts (nitrate and chloride) in ISO algal culture medium was followed over 72 h; i.e., the typical duration of algal toxicity tests. Fifty percent of the initial Cr spikes was lost from the solutions by 24 h, with losses up to 90% after 72 h. Monitoring of the temporal variability of Cr(III) concentrations in algal culture media appears necessary to better characterize the toxicity of trivalent chromium to algae.


Validity of the shortened Mood and Feelings Questionnaire in a community sample of children and adolescents: a preliminary research note.
The Mood and Feelings Questionnaire (MFQ) was designed to detect clinical depression in children and adolescents. Our aim was to investigate the relationship between symptom scores obtained using the short-version MFQ and psychiatric disorders in a non-clinical sample. Seventy-eight parents and 71 twins, who had completed the MFQ, were interviewed separately using a semistructured diagnostic interview, the Child and Adolescent Psychiatric Assessment. Parent-rated MFQ scores (MFQ-P) were found to distinguish those with ICD-10 (point biserial correlation = 0.345) and DSM-III-R depression (point biserial correlation = 0.369) from non-depressed cases. MFQ-P scores also differentiated depressed cases from those with 'other psychiatric diagnoses' (any anxiety disorder, oppositional defiant disorder and conduct disorder, hyperkinetic disorder/attention deficit hyperactivity disorder and adjustment disorder/post-traumatic disorder). The MFQ-P at the chosen cut-off point showed a sensitivity of 0.75 and specificity of 0.73 for an ICD-10 diagnosis of depression and a sensitivity of 0.86 and specificity of 0.87 for DSM-III-R depression. The number of self-rated reports (MFQ-C) was small, but overall the results suggest that self-rated MFQ scores may show less specificity. The MFQ-C at the selected cut-off point showed a sensitivity of 0.6 and specificity of 0.61 for ICD-10 depression, and a sensitivity of 0.75 and specificity of 0.74 for DSM-III-R depression.


A general strategy to inhibiting viral -1 frameshifting based on upstream attenuation duplex formation.
Viral -1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on -1 PRF for optimal propagation. Efficient eukaryotic -1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral -1 PRF stimulators have been developed. However, accessing particular -1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate -1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate -1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for -1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates -1 PRF stimulated by distinct -1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral -1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.


Economic analysis of adaptive strategies for flood risk management under climate change.
Climate change requires reconsideration of flood risk management strategies. Cost-benefit analysis (CBA), an economic decision-support tool, has been widely applied to assess these strategies. This paper aims to describe and discuss probabilistic extensions of CBA to identify welfare-maximising flood risk management strategies under climate change. First, uncertainty about the changes in return periods of hydro-meteorological extremes is introduced by probability-weighted climate scenarios. Second, the analysis is extended by learning about climate change impacts. Learning occurs upon the probabilistic arrival of information. We distinguish between learning from scientific progress, from statistical evidence and from flood disasters. These probabilistic extensions can be used to analyse and compare the economic efficiency and flexibility of flood risk management strategies under climate change. We offer a critical discussion of the scope of such extensions and options for increasing flexibility. We find that uncertainty reduction from scientific progress may reduce initial investments, while other types of learning may increase initial investments. This requires analysing effects of different types of learning. We also find that probabilistic information about climate change impacts and learning is imprecise. We conclude that risk-based CBA with learning improves the flexibility of flood risk management strategies under climate change. However, CBA provides subjective estimates of expected outcomes and reflects different decision-maker preferences than those captured in robustness analyses. We therefore advocate robustness analysis in addition to, or combined with, cost-benefit analysis to support local investment decisions on flood risk reduction and global strategies on allocation of adaptation funds for flood risk management.


The importance of peripheral vasoconstriction in influencing body temperatures and the part played by certain environmental factors: the effect of inhaled gases.
Core and peripheral temperatures have been studied in 88 dogs of mixed breeds anaesthetized with pentobarbitone. Hyperventilation with cold, dry oxygen was associated with a decrease in peripheral temperature, whilst normoventilation was without effect.


Pioglitazone, PPARγ agonist, attenuates experimental autoimmune neuritis.
Recent advances demonstrate peroxisome proliferator-activated receptors gamma (PPARγ) agonist, pioglitazone, as an anti-inflammatory drug. We investigated the effect of pioglitazone on experimental autoimmune neuritis (EAN) rats. Pioglitazone was given once daily (10 mg/kg) by oral gavage feeding from day 1-24 (suppressive group) and day 11-24 (therapeutic group). Pioglitazone ameliorated the clinical score of EAN, decreased expression of TNF-α, IFN-γ, and the activation of NF-κB, while increasing the expression of PPARγ and IL-4. Furthermore, we observed higher expression of PPARγ and IL-4 and lower expression of TNF-α, IFN-γ and reduced activation of NF-κB in suppressive group than those in the therapeutic group, which corresponds to lower clinical score and earlier disease recovery. Our data effectively demonstrate the anti-inflammatory properties of pioglitazone in EAN by inhibition of NF-κB signaling pathway.


Remission of nephrotic syndrome diminishes urinary plasmin content and abolishes activation of ENaC.
Urinary plasmin activates the epithelial Na(+) channel (ENaC) in vitro and may possibly be a mechanism of sodium retention in nephrotic syndrome (NS). This study used a paired design to test the hypothesis that remission of NS is associated with a decreased content of urinary plasmin and reduced ability of patients' urine to activate ENaC. Samples were collected during active NS and at stable remission from 20 patients with idiopathic NS, aged 9.1 ± 3.2 years. Plasminogen-plasmin concentration was measured with an enzyme-linked immunosorbent assay. Western immunoblotting for plasminogen-plasmin was performed in paired urine samples. The patch clamp technique was used to test the ability of urine to evoke an inward current on collecting duct cells and human lymphocytes. The urinary plasminogen-plasmin/creatinine ratio was 226 [95 % confidence interval (CI) 130-503] μg/mmol in nephrotic urine versus 9.5 (95 % CI 8-12) μg/mmol at remission (p < 0.001). Western immunoblotting confirmed the presence of active plasmin in urine collected during active NS, while samples collected at remission were negative. Nephrotic urine generated an inward amiloride- and α2-anti-plasmin- sensitive current, whereas the observed increase in current in urine collected at remission was significantly lower (201 ± 31 vs. 29 ± 10 %; p = 0.005). These findings support the hypothesis that aberrantly filtered plasminogen-plasmin may contribute to ENaC activation and mediate primary renal sodium retention during active childhood NS.


Protective role of NHE-3 inhibition in rat renal transplantation undergoing acute rejection.
Acute rejection in renal transplantation disturbs solute and volume maintenance in humans accompanied by delayed graft function and poor prognosis. We recently reported that decreased expression and function of Na+/H+ exchanger type 3 (NHE-3) in proximal tubules and epithelial Na+ channels and aquaporin 2 in collecting ducts are major mechanisms involved in Na+ and water imbalances shortly after transplantation in rat undergoing acute rejection. We performed kidney transplantations in rats with bilaterally nephrectomized recipients with acute rejection and, in addition, systemically administered a specific inhibitor of NHE-3 (NHE-I). NHE inhibition in acute renal failure was shown to improve tubular function and recovery. The aim of this therapy was to reduce energy consumption of the graft and preserve NHE-3 function. Imbalances in electrolyte excretion declined in NHE-I-treated animals and NHE-3 activity was preserved. Observed NHE-I-dependent changes in electrolyte excretion, polyuria, and reduced protein reabsorption in the acute postoperative phase are predictors of favorable graft outcome in humans.


Plants have isoforms for acyl carrier protein that are expressed differently in different tissues.
Two closely related isoforms of acyl carrier protein (I and II) have been purified from spinach leaves. Differences in the N-terminal amino acid sequence and amino acid composition indicate that these proteins are coded by different genes. The two spinach leaf isoforms have been resolved and characterized by ion-exchange high-performance liquid chromatography, by thin layer isoelectric focusing, and by differences in mobility upon polyacrylamide gel electrophoresis. Both isoforms are effectively bound by antibodies raised to acyl carrier protein I. However, in competition experiments isoform II is only about 40% effective in blocking isoform I binding to antibody. Therefore, the isoforms are immunologically related but hold only some antigenic sites in common. Immunoblot analysis ("Western blotting") of crude spinach leaf tissue extracts probed with antibody to acyl carrier protein I reveals both isoforms. In addition, both forms of acyl carrier protein are present in dark-grown leaf tissue and in isolated chloroplasts. However, in spinach seeds and roots only acyl carrier protein II can be detected. Similar results are observed with extracts of castor oil plant leaf and seed. Therefore, the expression of the two acyl carrier protein isoforms is tissue specific.


Treatment of purulent staphylococcal conjunctivitis in rabbits with autogenous vaccine.
Autogenous Staphylococcus aureus vaccine produced temporary clinical improvement in 4 cases of conjunctivitis and may have a role where drugs are inappropriate.