Loss of p53 in esophageal squamous cell carcinoma and the correlation with survival: analyses of gene mutations, protein expression, and loss of heterozygosity in Japanese patients.
A high frequency of p53 protein expression or gene mutation has been reported in the early stages of esophageal squamous cell carcinoma (ESCC), and thus loss of p53 function is thought to be very important in esophageal carcinogenesis. However, there is controversy surrounding the correlation between p53 dysfunction and ESCC tumor progression. The complexity arises from the different modalities, such as mutation analysis, immunohistochemistry, and the detection of loss of heterozygosity (LOH) at the p53 genomic locus. In this study, we comprehensively analyzed p53 gene mutation, p53 protein expression, and LOH at 17p13 in 94 surgically resected Japanese cases of ESCC. The frequency of p53 gene mutation was 60.6%. The rate of positive p53 protein expression was 56.4%. The frequency of LOH at 17p13 was 67.5%. There was a statistically significant correlation between the presence of a gene mutation and LOH, whereas, there was no significant correlation between gene mutation and protein expression. Despite the importance of loss of p53 function in esophageal carcinogenesis, none of the examined parameters, either singly or combined, correlated with overall survival. Taken together, p53 function is a primary target for esophageal carcinogenesis but there is no apparent correlation with the malignant phenotype in ESCC.


Open versus endovascular repair of abdominal aortic aneurysms: what does each really cost?
Endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) has emerged as an alternative to open repair (OR). The aim of this study was to compare the clinical outcomes and specific costs of these procedures since commercialization.A retrospective analysis of 119 consecutive infrarenal AAA repaired via an EVAR or an OR between July 2000 and September 2001 was performed. Patient charts were reviewed. Diagnostic-related group (DRG) classification and payer mix were identified. The hospital cost accounting system was accessed to obtain actual variable direct cost (AVDC) for the two groups. Percentages of the mean AVDC for the two groups were compared in the following cost categories: graft, operating room, radiology procedures and supplies, pharmacy, respiratory therapy, clinical laboratories, surgical floor, and monitored unit. Hospital profit margins were determined. Fifty-five patients underwent EVAR and 64 patients underwent OR. Mean aneurysm size was 5.5A cm (EVAR) and 6.1A cm (OR). Mean intensive care unit (ICU) stay was 0.09 days for EVAR vs. 3.5 days for OR ( p < 0.05). Mean length of stay (LOS) was 1.96 days for EVAR vs. 7.3 days for OR ( p < 0.05). Reimbursement was based on DRG 110, 47.3% in the EVAR and 79.7% in the OR group ( p < 0.05), and DRG 111, 50.9% in the EVAR group and 12.5% in the OR group ( p < 0.05). The payer mix showed no significant differences between the two groups. Mean AVDC for EVAR was 1.74 times that of OR. Significant differences in the distribution of costs were found in the following: graft costs (58% vs. 6.3%, p < 0.05), radiology procedures and supplies (3.9% vs. 0.1%, p < 0.05), pharmacy (1.9% vs. 10.5%, p < 0.05), and monitored unit (7.3% vs. 24.65%, p < 0.05) comparing EVAR vs. OR, respectively. Median cost of an endovascular graft was 22.4 times that of the standard graft for OR. Average hospital profit margins for an EVAR case was 49.5% vs. 88.6% for OR. Despite significant differences in monitored unit utilization, pharmacy services, and respiratory therapy services by the OR group, the cost of EVAR is appreciably more expensive. Furthermore, increased DRG reimbursement, and decreased ICU use and LOS do not compensate for the cost of EVAR. The main cost of EVAR is the cost of the graft itself. Hospital profit margins are acceptable with both the EVAR and OR procedures at this time; however, with proposed reductions in reimbursement, the ability to cover the cost of this new technology may be threatened.


An Overview of Human Resources and Capacity in Health Care Institutions in the Federation of Bosnia and Herzegovina in the Context of Responding to the COVID 19 Pandemic.
The organization of health care system on Cantonal level with the coordination from Federal level represents a real situation with the possibility of decentralization of health care system according to the experiences of developed countries. To make an overview of the situation at the primary and hospital health care level with the aim of assessing the existing human resources and capacity of health care institutions in FB&H, with which we entered in COVID-19 pandemic. This retrospective study presents the efficiency of health care in FB&H measured by number of medical doctors, and other medical staff during the time period of five years. Data of the Institute for Public Health FB&H were used. The Institute for Public Health FB&H is authorised by the law to conduct and implement statistical research in the field of health care in line with relevant laws and by-laws. The Institute is obliged to report on organisational structure, human resources and medical equipment. Presented data include the number of health care employees in medical institutions in FB&H in the period 2015-2019 per 100,000 inhabitants and their numbers in primary health care, family medicine, secondary and tertiary level of health care in 2019. The study also presents the number of doctors of medicine, specialists and medical residents in FB&H, the number of nurses of all profiles and levels of education as well as medical staff and other employees in the public health care system in FB&H in 2019. The COVID-19 pandemic in FB&H has confirmed the fact that human resources in health care are insufficient, especially in the field of public health and epidemiology. The availability of these health facilities and human resource is not uniform throughout the FB&H, which may affect the capacity of the health system in some parts of the FB&H to meet the needs of providing services during COVID-19 pandemic.


A case of a large solitary fibrous tumor in the thigh, displaying NAB2ex4-STAT6ex2 gene fusion.
A solitary fibrous tumor (SFT) is documented in several body sites. However, there are few reports on the radiological and corresponding histopathological, including immunohistochemical, features of SFT in the lower extremities. A 58-year-old male presented with a lump in his right thigh of 6 months duration. Plain radiograph revealed a soft tissue lesion in his right thigh, involving the adjacent mid-diaphysis and showing focal cortical thickening and calcification. Magnetic resonance imaging scans displayed two well-defined, T1-isointense and T2 heterogeneously hyperintense lesions, measuring together 15 cm in the intermuscular plane and the juxtacortical location along the mid-diaphyseal region of the right femur. Radiologically, the differential diagnoses considered were undifferentiated pleomorphic sarcoma and synovial sarcoma. Microscopic examination of the core biopsy and the resected tumor revealed a tumor composed of cells with oval to spindle-shaped nuclei in a variably collagenized stroma, including hyalinized blood vessels and focal dystrophic calcification. Mitotic figures were 4/10 high power fields. Immunohistochemically, the tumor cells were positive for CD34, BCL2, and STAT6. Diagnosis of malignant SFT was offered. The tumor displayed NAB2ex4-STAT6ex2 gene fusion on molecular testing. This constitutes a relatively uncommon case report of a large SFT in the thigh, including its radiological and pathological features, confirmed by STAT6 immunostaining. An SFT should be considered in cases of slow-growing, well-defined soft tissue tumors, which are isointense on T1 and heterogeneously hyperintense on T2-weighted sequences, and display calcification and cortical thickening of the adjacent bones. Various differential diagnoses and their treatment-related implications in such cases are discussed herewith.


Age-related changes in the ultrastructure of Bruch's membrane.
An ultrastructural study of Bruch's membrane in 68 human eyes including at least five individuals from each of ten decades of life showed that changes began in the second decade in macular specimens but were delayed in nonmacular specimens. All specimens from 20-year-old donors had altered macular Bruch's membranes. The severity of changes increased with age. The most common change for all ages was debris on both sides of the elastic layer. Drusen sites often showed no debris in the underlying outer collagenous zone, suggesting that drusen may result from failure of dispersal of the accumulated material at these sites. Secretion by pigment epithelium of a "linear basal deposit" is a late (after the age of 50 years) change.


Clinical aspects and treatment of pain in children and adolescents with cancer.
The aim of this study was to characterize the clinical aspects and the treatment of mild to severe pain in Brazilian children and adolescents with cancer. We evaluated the importance of classifying patients according to the phase of cancer treatment (diagnosis, treatment, recurrence, and end-of-life palliative care) and the opioid-related side effects. An institutional prospective study of 184 episodes of pain in children and adolescents with cancer was conducted. Pain was classified according to its cause, physiopathology and intensity. Treatment was based on the WHO guidelines for cancer pain relief. Pain scales were completed by 77% of the patients. Numerical scales were used by 49% of them. Morphine was given in 111 episodes for 2,758 patient days. Morphine doses had to be escalated when it was given to patients during end-of-life palliative care. Opioids were well tolerated with no severe side effects. Psychological dependence on morphine was found in 2% (2/111) of the cases. Pain control was satisfactory in 97% of the episodes. The WHO guidelines for cancer pain relief were effective in controlling pain in children and adolescents with cancer. Despite their low socioeconomic level, patients were able to quantify their pain using rating scales.


The innervation of the gastrointestinal tract of a chelonian reptile, Pseudemys scripta elegans. II. Distribution of neuropeptides in the myenteric plexus.
The myenteric plexus of the stomach, midgut and hindgut of the red-eared turtle, Pseudemys scripta elegans, has been investigated for the occurrence of immunoreactivity to nine neuropeptides. Neuropeptide Y (NPY)-, calcitonin gene-related peptide (CGRP)-, bombesin (BOM)- as well as substance P (SP)-like immunoreactivity (LI) were found in nerve fibres of all investigated gut regions. From all peptides investigated immunoreactivity for NPY was more pronounced. In the stomach NPY-LI was mainly found in the perikarya, while in the midgut region both NPY-immunoreactive (IR) somata and nerve fibres were revealed. The hindgut harboured few NPY-IR nerve cells and nerve fibres. A few SP-IR nerve cell bodies were observed in the stomach and midgut region. In the hindgut BOM-IR neuronal cell bodies were found. Neuromedin U (NMU)-LI was mainly observed in the stomach region, revealing both immunoreactive perikarya and nerve fibres. Immunoreactivity for vasoactive intestinal polypeptide, somatostatin, galanin and enkephalin could not be detected so far. Double labelling experiments revealed the coexistence of CGRP and SP in some nerve fibres in all three gut regions examined. Some SP-IR fibres in the midgut were immunoreactive for NMU.


[Menopause, menopause hormone therapy and osteoporosis. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines].
Postmenopausal osteoporosis is a frequent clinical condition, which affects nearly 1 in 3 women. Estrogen deficiency leads to rapid bone loss, which is maximal within the first years after the menopause transition and can be prevented by menopause hormone therapy (MHT). Assessment of the individual risk of osteoporosis is primarily based on the measurement of bone mineral density (BMD) at the spine and femur by DXA. Clinical risk factors (CRFs) for fractures taken either alone or in combination in the FRAX score were shown not to reliably predict fractures and/or osteoporosis (as defined by a T-score<-2.5) in early postmenopausal women. If DXA measurement is indicated in all women with CRFs for fractures, it can be proposed on a case-by-case basis, when knowledge of BMD is likely to condition the management of women at the beginning of menopause, particularly the benefit-risk balance of MHT. MHT prevents both bone loss and degradation of the bone microarchitecture in early menopause. It significantly reduces the risk of fracture at all bone sites by 20 to 40% regardless of basal level of risk with an estrogen-dependent dose-effect. Given the inter-individual variability in bone response, individual monitoring of the bone effect of MHT is warranted when prescribed for the prevention of osteoporosis. This monitoring is based on repeated measurement of lumbar and femoral BMD (on the same DXA measurement system) after 2years of MHT, the response criterion being no significant bone loss. Discontinuation of treatment is associated with a resumption of transient bone loss although there is a large variability in the rate of bone loss among women. Basically, there is a return to the level of fracture risk comparable to that of in untreated woman of the same age within 2 to 5years. Therefore, when MHT is prescribed for the prevention of osteoporosis in women with an increased risk at the beginning of menopause, measurement of BMD is recommended when MHT is stopped in order to consider further management of the risk of fracture whenever necessary (with possibly another anti-osteoporotic treatment).


Explaining the formation of a plateau in rotavirus vaccine impact on rotavirus hospitalisations in Belgium.
Observational data on the reduction in hospitalisations after rotavirus vaccine introduction in Belgium suggest that vaccine impact plateaued at an unexpectedly high residual hospitalisation rate. The objective of this analysis was to identify factors that influence real-world vaccine impact. Data were collected on hospitalisations in children aged ≤ 5 years with rotavirus disease from 11 hospitals since 2005 (the RotaBIS study). The universal rotavirus vaccination campaign started late in 2006. A mathematical model simulated rotavirus hospitalisations in different age groups using vaccine efficacy and herd effect, influenced by vaccine coverage, vaccine waning, and secondary infection sources. The model used optimisation analysis to fit the simulated curve to the observed data, applying Solver add-in software. It also simulated an 'ideal' vaccine introduction maximising hospitalisation reduction (maximum coverage, maximum herd effect, no waning), and compared this with the best-fit simulated curve. Modifying model input values identified factors with the largest impact on hospitalisations. Compared with the 'ideal' simulation, observed data showed a slower decline in hospitalisations and levelled off after three years at a higher residual hospitalisation rate. The slower initial decline was explained by the herd effect in unvaccinated children. The higher residual hospitalisation rate was explained by starting the vaccine programme in November, near the rotavirus seasonal peak. This resulted in low accumulated vaccine coverage during the first rotavirus disease peak season, with the consequential appearance of secondary infection sources. This in turn reduced the herd effect, resulting in a diminished net impact. Our results indicate that countries wishing to maximise the impact of rotavirus vaccination should start vaccinating well ahead of the rotavirus seasonal disease peak. This maximises herd effect during the first year leading to rapid and high reduction in hospitalisations. Secondary infection sources explain the observed data in Belgium better than vaccine waning.


Volumetric absorptive microsampling as alternative sampling technique for renal function assessment in the paediatric population using iohexol.
The glomerular filtration rate (GFR) is considered the best overall index for the renal function. Currently, one of the most promising exogenous markers for GFR assessment is iohexol. In this study, the suitability of volumetric absorptive microsampling (VAMS) as alternative for the conventional blood sampling and quantification of iohexol in paediatric plasma was assessed. Therefore, a new, fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed. Subsequently, the clinical suitability was evaluated in 20 paediatric patients by comparing plasma iohexol concentrations and associated GFR values obtained by the VAMS method with those obtained by conventional blood sampling and quantification of iohexol in plasma. The developed, simple and cost-effective LC-MS/MS-method fulfilled all pre-set validation acceptance criteria. Iohexol could be accurately quantified within a haematocrit range of 20-60% and long-term stability of iohexol in VAMS was demonstrated up to 245 days under different storage temperatures. Both iohexol plasma concentrations (r = 0.98, mean bias: -4.20%) and derived GFR values (r = 0.99; mean bias: 1.31%), obtained by a conventional plasma and the VAMS method, demonstrated good correlation and acceptable bias. The agreement between the two methods was especially good for GFR values higher than 60 mL/min/1.73 m2. Nevertheless, for GFR values <60 mL/min/1.73 m2 the accuracy compared to the plasma method was lower. However, small adjustments to the sampling protocol could probably solve this problem.


Focal adhesion kinase (FAK) promotes cholangiocarcinoma development and progression via YAP activation.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is upregulated in many tumor types and is a promising target for cancer therapy. Herein, we elucidated the functional role of FAK in intrahepatic cholangiocarcinoma (iCCA) development and progression. Expression levels and activation status of FAK were determined in human iCCA samples. The functional contribution of FAK to Akt/YAP murine iCCA initiation and progression was investigated using conditional Fak knockout mice and constitutive Cre or inducible Cre mice, respectively. The oncogenic potential of FAK was further examined via overexpression of FAK in mice. In vitro cell line studies and in vivo drug treatment were applied to address the therapeutic potential of targeting FAK for iCCA treatment. FAK was ubiquitously upregulated and activated in iCCA lesions. Ablation of FAK strongly delayed Akt/YAP-driven mouse iCCA initiation. FAK overexpression synergized with activated AKT to promote iCCA development and accelerated Akt/Jag1-driven cholangiocarcinogenesis. Mechanistically, FAK was required for YAP(Y357) phosphorylation, supporting the role of FAK as a central YAP regulator in iCCA. Significantly, ablation of FAK after Akt/YAP-dependent iCCA formation strongly suppressed tumor progression in mice. Furthermore, a remarkable iCCA growth reduction was achieved when a FAK inhibitor and palbociclib, a CDK4/6 inhibitor, were administered simultaneously in human iCCA cell lines and Akt/YAP mice. FAK activation contributes to the initiation and progression of iCCA by inducing the YAP proto-oncogene. Targeting FAK, either alone or in combination with anti-CDK4/6 inhibitors, may be an effective strategy for iCCA treatment. We found that the protein FAK (focal adhesion kinase) is upregulated and activated in human and mouse intrahepatic cholangiocarcinoma samples. FAK promotes intrahepatic cholangiocarcinoma development, whereas deletion of FAK strongly suppresses its initiation and progression. Combined FAK and CDK4/6 inhibitor treatment had a strong anti-cancer effect in in vitro and in vivo models. This combination therapy might represent a valuable and novel treatment against human intrahepatic cholangiocarcinoma.


Confrontation naming in parkinsonian patients: post-operative anomia revisited.
Forty-three consecutively admitted Parkinsonian patients, of whom over a third had undergone stereotactic surgery about a decade previously, and a small control group were given a confrontation naming task. A number of comparisons were made, under the rubrics of success in naming, types of error and response latency, in an attempt to ascertain whether evidence of post-operative anomia could be detected. No such evidence was found. However, Parkinsonian lesions were shown to exert a constant quantitative effect on performance in the confrontation naming of objects.


Generic products of antiepileptic drugs (AEDs): is it an issue?
The availability of generic products of antiepileptic drugs (AEDs) has raised the following concerns: (1) Do generic AEDs work as well as brand AEDs in terms of their efficacy, safety and quality? (2) Can generic AEDs be used as substitutions for brand AEDs? and (3) Can generic products of AEDs be used interchangeably? The traditional average bioequivalence analysis addresses concern 1 but does not provide a complete adequate response to concerns 2 and 3. Drug interchangeability can be classified as drug prescribability or drug switchability. Drug prescribability refers to the situation where a patient is treated for the first time so that either a brand or a bioequivalent generic AED can be chosen. Drug switchability refers to the situation in which a brand AED is switched to a bioequivalent generic product of the same AED. The traditional average bioequivalence approach is sufficient to evaluate the prescribability of generic products, but does not ensure the switchability between prescribable formulations. The necessity of assuring switchability of two formulations can be addressed by individual bioequivalence. While the switch to generic AEDs is well tolerated by many patients and in general cost-effective, seizure control should not be sacrificed on the basis of cost alone, as the major end point in treating epilepsy with AEDs is seizure control without side effects. Until we have individual (within patient) bioequivalence data on generic AEDs and/or the tools to a priori identify the subset of patients susceptible to the generic switch, a switch of AED products in seizure-free patients is not recommended.


[Time course of blood glucose levels in rats after intraperitoneal injection of a dose of serotonin].
The injection of 20 mg/Kg of serotonin intraperitoneally, in rats, elicits a progressive and marked increase of blood glucose after 30, 60 and 90 minutes. These results, according with previous experiments of the same authors, put yet in evidence that the serotonin has a clear influence on glucose metabolism.


[Interest of dermal substitute (Matriderm ©) to cover long fingers after congenital syndactyly: About 20 commissures].
Surgical treatment of congenital syndactylies is based on the creation of a new commissure - with a commissural flap - and on the management of fingers lateral faces - with mirror zigzag incisions. Lateral skin defects are covered by full-thickness skin graft. Since their discover 30 years ago, dermal substitutes applications have been enlarged. We have wandered if these technique could be interesting for the treatment of these lateral skin defects. We have launched a monocentric and retrospective study with only one surgeon. The assessor and the operator were different. Included patients have a simple or complex congenital syndactyly, complete or not, associated with a syndrome or not. Children with a first web space syndactyly were excluded. Surgical treatment was performed with a dorsal commissural flap, with mirror incisions and with a lateral skin defects coverage by dermal substitute (Matriderm(©)) and split-thickness skin graft taken from the scalp. The initial assessment criterion was the quality of the scare measured by the OSAS score. Web creep (Whitney's scale) and time of surgery were two minor criteria. Twenty commissures (11 children) have been included between 2008 and 2013. Fourteen complex syndactylies were noted. The average aftercare was equal to 2.7 years (0.5-5.5 years). Interventions were performed at the age of 1.8 years (0.5-4 years). Surgical time was equal to 44.6 min (22-95 min). Patients OSAS score was 11.9 (6-18). It was 12.2 (60-20) for complex forms and 11.9 (10-16) for simple forms. Graft weren't hairy. There was no complication on the donor site. Whitney's score was 1.2 (0-3) and three web spaces were reoperated. We think that the use of dermal substitute Matriderm(©) is a new and serious alternative to treat congenital syndactylies. Results have to be confirmed by a new study which would compare this material to full-thickness skin graft, gold standard technique for these skin defects.


Prognosis in cardiogenic shock after acute myocardial infarction in the interventional era.
The purpose of this study is to describe the outcome in cardiogenic shock treated with aggressive reperfusion therapy and to identify factors predictive of in-hospital and long-term mortality. Cardiogenic shock is the most common cause of death in patients admitted to the coronary care unit. Although studies have reported lower mortality rates in shock treated with angioplasty, few studies have described a cohort of patients with shock who were not selected because they were most likely to benefit from reperfusion therapy. A consecutive series of 200 patients admitted with acute myocardial infarction complicated by cardiogenic shock were studied. The in-hospital mortality rate was 53%. Variables with significant univariable association with in-hospital death included patency of the infarct-related artery, patient age, lowest cardiac index, highest arteriovenous oxygen difference and left main coronary artery disease. The most important independent predictors of in-hospital death were patency of the infarct-related artery, cardiac index and peak creatine kinase, MB fraction. The mortality rate in patients with patent infarct-related arteries was 33% versus 75% in those with closed arteries and 84% in those in whom arterial patency was unknown. Patients who survived to hospital discharge were followed up for a median of 2 years, with a mortality rate of 18% after 1 year. The best descriptors of the relation between these variables and postdischarge mortality included age, peak creatine kinase, ejection fraction and patency of the infarct-related artery. In a large consecutive series of patients with cardiogenic shock with complete follow-up, patency of the infarct-related artery was most strongly associated with in-hospital and long-term mortality. This finding supports an aggressive interventional strategy in patients with cardiogenic shock.


Triple quantitative detection of three inflammatory biomarkers with a biotin-streptavidin-phycoerythrin based lateral flow immunoassay.
Quantified inflammatory biomarkers are effective clinical strategy for correct and reasonable drug treatment. In the study, a triple lateral flow immunoassay (triple LFIA) had firstly been developed for specific and simultaneous detection of three pivotal inflammatory biomarkers (PCT, CRP and SAA) via biotin-streptavidin-phycoerythrin signal amplification system in one strip. The developed triple LFIA adopted phycoerythrin (PE) as chromophore to eliminate auto-fluorescence interference from plasma biomolecules and anti-PE mAb as single control line to reduce the nonspecific adsorption, which featured particular advantages in high sensitivity and specificity in a large range of analyte concentrations with the LODs of 0.106 ng/mL for PCT, 0.345 μg/mL for CRP and 3.112 μg/mL SAA, respectively. And the linear quantitative detection ranges were from 0.106 to 100 ng/mL, from 0.345 to 200 μg/mL, and from 3.112 to 200 μg/mL, respectively. Compared to commercial chemiluminescence immunoassay method, the correlations for tested PCT, CRP and SAA in 108 clinical samples were 0.989, 0.987 and 0.988, respectively. In summary, we had proposed a rapid and accurate plasma detection to measure inflammation factors, which facilitated the clinical value to achieve precise treatment.


Ownership of change: Participatory development of a novel latent construct for neighborhoods and health equity research.
Processes of neighborhood change are important determinants of health. One salient dimension of the experience of neighborhood changes is a person's evolving sense of empowerment over the changes around them, such as development of new housing or shifts in economic opportunity. Community residents collaborating on a Participatory Action Research study developed the novel construct "ownership of change" to capture this psychosocial process, and hypothesized that it may help explain the relationship between neighborhood change and health. In this paper, we describe our participatory process for developing a way to measure ownership of change, explore the construct's validity, test the hypothesis that it is associated with health, and analyze qualitative data to understand the process through which one's sense of ownership of change is produced. We argue that the construct is useful for studying the role of neighborhood changes in shaping health, and that building ownership over neighborhood change must be a key dimension of urban planning and policy for health equity.


Self-administration of parenteral ketorolac tromethamine for head pain.
Sixty-one separate self-injections of ketorolac tromethamine (Toradol) by 16 patients diagnosed with episodic migraine with or without aura were evaluated over a 90-day period for safety, efficacy of pain reduction, and the ability of this therapy program to prevent the necessitation of emergency room acute care. Prior to initiation of treatment, patients were formally instructed on intramuscular injection techniques by a member of our nursing staff. Patients were instructed to call upon the onset of a severe headache interfering with daily functioning and, then, were permitted to proceed with the injection. Headache intensity ratings were collected prior to injection and intermittently for the following twenty-four hours. The results demonstrate safety and efficacy of this form of therapy. A significant percent of ketorolac usages (64%) resulted in a good response and significant reduction in head pain. Twenty-three percent of ketorolac usages resulted in a mild response and only 13% of usages provided no relief. Furthermore, 13% of all usages failed to prevent the necessitation for emergency room treatment. The results are discussed in terms of the impact of self-injection on pain relief and substantial cost-reduction by decreasing emergency room utilization.


Are herbarium mosses reliable indicators of historical nitrogen deposition?
Mosses collected decades ago and stored in herbaria are often used to assess historical nitrogen deposition. This method is effectively based on the assumption that tissue N concentration remains constant during storage. The present study raises serious doubt about the generality of that assumption. We measured tissue N and C concentrations as well as δ15N, δ13C, Pb and Mg in herbarium and present day samples of seven bryophyte species from six sites across Denmark. While an increase in nitrogen deposition during the last century is well-documented for the study site, we surprisingly found foliar N concentration to be higher in historical samples than in modern samples. Based on δ15N values and Pb concentration, we find nitrogen contamination of herbarium specimens during storage to be the most likely cause, possibly in combination with dilution though growth and/or decomposition during storage. We suggest ways to assess contamination and recommend caution to be taken when using herbarium specimens to assess historical pollution if exposure during storage cannot be ruled out.


Risk factors for bit-related lesions in Finnish trotting horses.
Bit-related lesions in competition horses have been documented, but little evidence exists concerning their potential risk factors. To explore potential risk factors for oral lesions in Finnish trotters. Cross-sectional study. The rostral part of the mouth of 261 horses (151 Standardbreds, 78 Finnhorses and 32 ponies) was examined after a harness race. Information on bit type, equipment and race performance was collected. A multivariable logistic regression model of Standardbreds and Finnhorses showed a higher risk of moderate or severe oral lesion status associated with horses wearing a Crescendo bit (n = 38, OR 3.6, CI 1.4-8.9), a mullen mouth regulator bit (n = 25, OR 9.9, CI 2.2-45) or a straight plastic bit (n = 14, OR 13.7, CI 1.75-110) compared with horses wearing a snaffle trotting bit (n = 98, P = .002). Bar lesions (67 horses) were more common in horses wearing unjointed bits than in horses wearing jointed bits (Fisher's exact test P < .001). Lesions in the buccal area and the inner lip commissures were not associated with bit type. Using a tongue-tie or an overcheck, galloping, placement in the top three or money earned in the race were not associated with lesion risk. The sample size for certain bit types was insufficient for statistical analysis. Moderate and severe oral lesion status was more common in horses wearing a Crescendo bit, a mullen mouth regulator bit or a straight plastic bit than in horses wearing a single-jointed snaffle trotting bit. However, lesions were observed regardless of bit type. Further studies on rein tension, the interaction between bit type and rein tension and prevention of mouth lesions in trotters are warranted.


Termination of pregnancy for fetal anomaly after 23 weeks of gestation: a European register-based study.
To determine the prevalence of termination of pregnancy for fetal anomaly (TOPFA) after 23 weeks of gestation in European countries, and describe the spectrum of anomalies for which late TOPFA is recorded. Population-based study. Twelve European countries. Nineteen registries of congenital anomaly in 12 European countries between 2000 and 2005. The number of total births covered was 2 695 832. TOPFAs in singleton pregnancies from the European Surveillance of Congenital Anomalies and Twins (EUROCAT) database. The prevalence of TOPFA and type of anomaly. There were 10 233 TOPFAs, 678 (6.6%) of which were performed at 24 weeks or more. The rate of TOPFA before 24 weeks was 3.4 per 1000 births, at 24-25 weeks 0.14 per 1000 births and at 26 weeks or more 0.11 per 1000 births. There was significant variation in the prevalence of TOPFA at >or=24 weeks between countries (P < 0.001), with all countries in the range 0-0.55 per 1000 births, except France (Paris) at 2.65 per 1000 births. The large majority of late TOPFAs had a gestational age of 24-27 weeks (516/678, 76%). The proportion of TOPFAs from 24 weeks or more varied by type of anomaly, with 4% of all TOPFAs for chromosomal anomalies and 9% of all TOPFAs for nonchromosomal anomalies resulting in late TOPFA (P < 0.001). For transposition of the great arteries, single ventricle, hypoplastic left heart and hydrocephaly, the percentage of late TOPFA was 12-23%. The median time interval between diagnosis and late TOPFA was 2 weeks for most anomalies, but longer (>or=5 weeks) for diaphragmatic hernia, omphalocoele, arthrogryposis multiplex and Turner's syndrome. Late TOPFA is rare in Europe, and varies in prevalence between countries. Compared with earlier TOPFA, late TOPFA is more often performed for a nonchromosomal isolated major structural anomaly and less often for a fetus with a chromosomal syndrome or multiple anomalies.


Cost-effectiveness of West Nile virus vaccination.
West Nile virus (WNV) was first detected in the Western Hemisphere in 1999 in New York City. From 1999 through 2004, >16,600 cases of WNV-related illnesses were reported in the United States, of which >7,000 were neuroinvasive disease and >600 were fatal. Several approaches are under way to develop a human vaccine. Through simulations and sensitivity analysis that incorporated uncertainties regarding future transmission patterns of WNV and costs of health outcomes, we estimated that the range of values for the cost per case of WNV illness prevented by vaccination was US 20,000 dollars-59,000 dollars(mean 36,000 dollars). Cost-effectiveness was most sensitive to changes in the risk for infection, probability of symptomatic illness, and vaccination cost. Analysis indicated that universal vaccination against WNV disease would be unlikely to result in societal monetary savings unless disease incidence increases substantially over what has been seen in the past 6 years.


Prospective study on the relationship between cervical neoplasia and herpes simplex type 2 virus. III. Presence of herpes simplex type-2 antibody in sera of subjects who developed cervical neoplasia later in the study.
Paired sera taken from 63 subjects who developed cervical neoplasia in the course of a prospective study on this disease were examined for the presence of herpes simplex virus type 2 (HSV-2) antibody. The first serum was taken at enrollment into the study, while the second was obtained after development of the disease, i.e. 2-4 years later. Simultaneously, paired sera from a group of control subjects, who remained free of any cytological and colposcopical abnormalities throughout the study, were also investigated. Controls were matched with patients by age, age at first intercourse, number of sexual partners, smoking habits and history of diathermoelectrocoagulation of ectopic epithelium and transformation zone of the cervix. The first sera from these subjects were obtained at enrollment while the second ones were taken at the end of the study, i.e. 5 to 7 years later. Antibody titres were remarkably stable in both patients and control subjects. Seroconversions from HSV-2 negativity to HSV-2 positivity as measured by the increase in the II/I ratio or development of antibody reactive with HSV-2-specific glycoprotein G were rare and no significant differences between the patients and control subjects were detected. This indicates that the development of the disease was apparently not followed by immediate or early activation of latent HSV-2 infection.


Pharmaceutically relevant (hetero)cyclic compounds and natural products from lignin-derived monomers: Present and perspectives.
Lignin, the richest source of renewable aromatics on the planet, is an intriguing raw material for the construction of value-added aromatics. In the past decade, much progress has been made regarding the development of efficient lignin depolymerization methods, able to produce specific monophenol derivatives in high-enough selectivity and yields. This now serves as an excellent basis for developing powerful downstream conversion strategies toward a wide range of products, including fine chemical building blocks. The inherent structural features of lignin-derived platform chemicals undoubtedly inspire the development of novel, creative, atom-economic synthetic routes toward biologically active molecules or natural products. In this perspective we attempt to bridge the structural features of lignin-derived platform chemicals with existing synthetic strategies toward the construction of heterocycles and provide a summary of efforts for the production of natural products from aromatics that can be, in principle, obtained from lignin. Last, we comment on the latest efforts that present entire value-chains from wood to valuable pharmaceutically relevant compounds.


Increasing prevalence of overweight among Seychelles children, 1998-2002.
To examine the prevalence and trends in excess weight among children in the Seychelles. Serial surveys of weight and height were conducted each year between 1998-2002 in all students attending four school grades (crèche, 4th, 7th and 10th years of compulsory school). Overweight and obesity were defined using age-specific body mass index (BMI) criteria of the International Obesity Task Force. Two questions explored physical activity at leisure time and daily walking time. From an eligible total of 32 077 observations between 1998-2002, data were available in 22 694 (71%), which corresponded to 17 627 separate children. Median age in the four grades was respectively 5.5, 9.2, 12.6, and 15.8 years. The overall prevalence of excess weight ('overweight' and 'obese' categories combined) was 10.5% in boys and 16.4% in girls. From 1998 to 2002, the prevalence of excess weight increased from 8.4% to 11.8% in boys and from 11.9% to 18.4% in girls. The increase of excess weight over calendar years was particularly marked among the younger children. Only a quarter of children reported walking at least 30minutes per day. Leisure physical activity was inversely associated with excess body weight. The prevalence of excess body weight was high among school children of Seychelles and increased substantially over a five-year period. This calls for prompt and energetic policies and programs to promote physical activity and healthy nutrition among children.


Pulmonary hypertension in systemic sclerosis with usual interstitial pneumonia.
Retrospective study comparing pulmonary hypertension risk in systemic sclerosis (SSc) and non-SSc interstitial lung disease patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Retrospective analysis of 144 interstitial lung disease patients, 53 SSc (32 UIP and 21 NSIP) and 91 non-SSc (47 UIP and 44 NSIP). Pulmonary hypertension was diagnosed as pulmonary systolic artery pressure (PAPs) > 25 mmHg. All SSc and non-SSc patients with pulmonary hypertension were classified WHO Group 3. Pulmonary hypertension was identified in 21/32 (65.6%), 9/21 (42.8%), 14/47 (29.7%), and 28/44 (45.4%) SSc-UIP, SSc-NSIP, control-UIP, and control-NSIP groups, respectively. PAPs mean of SSc-UIP group was higher than control-UIP group (32.6 ± 9.8 vs 28.5 ± 6.6, p-value = 0.02). PAPs mean of SSc-NSIP group was lower than control-NSIP group (27.0 ± 7.1 vs 33.9 ± 8.8, p = 0.002). Frequency of patients with PAP > 25 mmHg in SSc-UIP group was 60% higher in comparison to control-UIP (OR = 1.62, 95% CI 0.51-5.16) and SSc-NSIP (OR = 1.60, 95% CI 0.45-5.70) groups. Logistic regression analysis estimating the linear trend per ten-unit increase in PAPs levels demonstrated an increment for the SSc-UIP group compared to the control-UIP (OR = 2.64, 95% CI 1.25-5.58, p = 0.01) and the control-NSIP (OR = 6.34, 95% CI 2.82-14.3, p < 0.001) groups. The case-control study confirms that pulmonary hypertension is frequently found in SSc patients and demonstrates, for the first time, a significant increased risk of pulmonary hypertension among SSc-UIP patients.


Interplay of carbon dioxide and peroxide metabolism in mammalian cells.
The carbon dioxide/bicarbonate (CO2/HCO3-) molecular pair is ubiquitous in mammalian cells and tissues, mainly as a result of oxidative decarboxylation reactions that occur during intermediary metabolism. CO2 is in rapid equilibrium with HCO3-via the hydration reaction catalyzed by carbonic anhydrases. Far from being an inert compound in redox biology, CO2 enhances or redirects the reactivity of peroxides, modulating the velocity, extent, and type of one- and two-electron oxidation reactions mediated by hydrogen peroxide (H2O2) and peroxynitrite (ONOO-/ONOOH). Herein, we review the biochemical mechanisms by which CO2 engages in peroxide-dependent reactions, free radical production, redox signaling, and oxidative damage. First, we cover the metabolic formation of CO2 and its connection to peroxide formation and decomposition. Next, the reaction mechanisms, kinetics, and processes by which the CO2/peroxide interplay modulates mammalian cell redox biology are scrutinized in-depth. Importantly, CO2 also regulates gene expression related to redox and nitric oxide metabolism and as such influences oxidative and inflammatory processes. Accumulated biochemical evidence in vitro, in cellula, and in vivo unambiguously show that the CO2 and peroxide metabolic pathways are intertwined and together participate in key redox events in mammalian cells.


THE ROLE OF AMINO ACIDS AND AMIDES IN THE METABOLISM OF AMMONIUM ABSORBED BY ZEA MAYS L.
When corn seedlings, previously depleted in soluble nitrogen constituents, are forced to absorb large quantities of ammonium nitrogen, soluble compounds accumulate in the sap. Asparagine, glutamine, one or more amino acids and undetermined compounds are synthesized. Ammonia does not accumulate until these constituents have reached a relatively high level.


A vertical flow microarray chip based on SERS nanotags for rapid and ultrasensitive quantification of α-fetoprotein and carcinoembryonic antigen.
A vertical flow microarray chip is described that uses core-shell SERS nanotags as tags for ultrasensitive quantification of the tumor markers α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) by detecting the intensity of the specific Raman bands at 592 cm-1. The nanotags warrant high sensitivity, and the use of porous nitrocellulose warrants a high surface-to-volume ratio. The linear dynamic ranges are 0.1 ng mL-1 - 10 μg mL-1 for both AFP and CEA, and the limits of detection) are 0.27 pg mL-1 and 0.96 pg mL-1, respectively. Quantification is rapid and can be performed without preconcentration. Graphical abstract Schematic representation of a vertical flow microarray chip using AuNBA@Ag SERS nanotags (where NBA stands for Nile blue A) as labels for rapid, ultrasensitive, and simultaneous detection of tumor biomarkers CEA and AFP.


Autonomous planning and control of soft untethered grippers in unstructured environments.
The use of small, maneuverable, untethered and reconfigurable robots could provide numerous advantages in various micromanipulation tasks. Examples include microassembly, pick-and-place of fragile micro-objects for lab-on-a-chip applications, assisted hatching for in-vitro fertilization and minimally invasive surgery. This study assesses the potential of soft untethered magnetic grippers as alternatives or complements to conventional tethered or rigid micromanipulators. We demonstrate closed-loop control of untethered grippers and automated pick-and-place of biological material on porcine tissue in an unstructured environment. We also demonstrate the ability of the soft grippers to recognize and sort non-biological micro-scale objects. The fully autonomous nature of the experiments is made possible by the integration of planning and decision-making algorithms, as well as by closed-loop temperature and electromagnetic motion control. The grippers are capable of completing pick-and-place tasks of biological material at an average velocity of 1.8 ±0.71 mm/s and a drop-off error of 0.62 ±0.22 mm. Color-sensitive sorting of three micro-scale objects is completed at a velocity of 1.21 ±0.68 mm/s and a drop-off error of 0.85 ±0.41 mm. Our findings suggest that improved autonomous untethered grippers could augment the capabilities of current soft-robotic instruments especially in advancedtasks involving manipulation.


[Eye structure of cavernicolous populations ofAstyanax fasciatus : Contribution to the problems of degenerative evolution].
1. The characidAstyanax fasciatus, which has good, fully pigmented eyes is the ancestral form of a series of cave descendents, whose melanin pigment and eyes are reduced almost completely. Eye rudiments of two cave populations ("Anoptichthysantrobius" = population of Pachon and "A. hubbsi" = population of Sabinos) were examined anatomically. 2. Variabilities of eye types of both populations do not differ. Those developed best show a retina, which consists of all layers typical for teleostian eyes, except for the outer nuclear and outer reticular layers. The optic nerve is connected with the brain. The most degenerate eyes of all are those which have lost the optic nerve and show some tissue of unidentified character. 3. Within the eye itself there are correlations: large ones are less degenerate than small ones. 4. Size and degree of differentiation of the eyes of these cave fish are obviously dependent on genetic and inductive correlations, but also on environmental factors, such as light. 5. The E1-hybrids of the two cave forms demonstrate that they are genetically different because of separate evolution. This difference cannot be seen in the morphology of eye rudiments: there are more similarities than differences. The phenotypical divergences of eye rudiments between the two populations as observed by Peters and Peters (1966) are non-existent, and were obviously caused by an unexpected degree of modificability. 6. The genetic basis of eyes results developmentally physiologically in a special pattern of organisation. Phenotypically it reacts on all degenerative mutations alike. Therefore eyes degenerate in a trend. This pattern of organisation seems to be different in every species. Cavernicolous Amblyopsidae, for example, show similarities of structures of degenerate eyes, but they differ notably from those ofAstyanax cave populations.


Seizures produced by pilocarpine: neuropathological sequelae and activity of glutamate decarboxylase in the rat forebrain.
Morphological analysis of brains from rats receiving a convulsant dose of the muscarinic cholinergic agonist, pilocarpine hydrochloride (380 mg/kg), revealed a widespread damage to the forebrain as assessed by light microscopy 5-7 days after seizures. The substantia nigra, olfactory cortex, amygdala, hippocampus, septum, temporal cortex and thalamus underwent prominent morphological injury and cell loss. A concurrent assessment of the activity of L-glutamate decarboxylase (GAD), the gamma-aminobutyrate (GABA) synthesizing enzyme, demonstrated marked deficits in GAD activity in the brain regions undergoing morphological insult. Diazepam, 10 mg/kg, and scopolamine hydrochloride, 10 mg/kg, administered 30 min prior to the injection of pilocarpine, 380 mg/kg, prevented acute behavioral and electrographic, and long-term morphological and biochemical sequelae of seizures. These findings suggest that the muscarinic antagonist, scopolamine, and the anticonvulsant benzodiazepine, diazepam, may aid in preventing extensive brain damage related to pathological muscarinic cholinergic overactivity. The similarity of the topography of the damage and deficits in the GAD activity in brains of rats treated with pilocarpine indicates that GABAergic neurons are lost in the subregions of the brain preferentially sensitive to the convulsant action of pilocarpine.


Novel cfDNA Methylation Biomarkers Reveal Delayed Cardiac Cell Death after Open-heart Surgery.
The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions.


Hemoglobin concentration is associated with the incidence of metabolic syndrome.
An association between hemoglobin and metabolic syndrome (MetS) has been reported. However, the relationships between hemoglobin and individual MetS components remain unclear. Therefore, we investigated these associations at baseline and at the 3-year follow-up. We enrolled 9960 middle-aged and elderly subjects (6726 women and 3234 men) and performed a 3-year follow-up cohort study. All subjects completed a questionnaire and underwent anthropometric measurements and laboratory tests. Logistic regression models were developed to assess the association between hemoglobin and MetS and its components. MetS was present in 45.1% of women and 41.4% of men at baseline. The hemoglobin concentration was positively correlated with SBP, DBP, TGs, WC, FPG, insulin, HOMA-IR, BMI and uric acid (p < 0.05). The mean hemoglobin concentration was higher in subjects with hypertension, high TGs, abdominal obesity or elevated FPG (p < 0.01). At follow-up, elevated hemoglobin correlated with an increased incidence and ORs for MetS, high TGs, low HDL-c, hyperuricemia and NAFLD but not abdominal obesity, BP or FPG in women. Increased hemoglobin corresponded with an increased incidence and ORs for MetS, abdominal obesity, low HDL-c, hyperuricemia and NAFLD but not BP, high TGs or FPG in men. Hemoglobin may play a role in predicting new-onset MetS in both women and men. Hemoglobin was notably correlated with future risk of high TGs, low HDL-c, hyperuricemia, and NAFLD among women and abdominal obesity, low HDL-c, hyperuricemia, and NAFLD among men.


Apoptotic proteins with non-apoptotic activity: expression and function in cancer.
Apoptosis is a process of programmed cell death in which a cell commits suicide while maintaining the integrity and architecture of the tissue as a whole. Apoptosis involves activation of one of two major pathways: the extrinsic pathway, where extracellular pro-apoptotic signals, transduced through plasma membrane death receptors, activate a caspase cascade leading to apoptosis. The second, the intrinsic apoptotic pathway, where damaged DNA, oxidative stress, or chemicals, induce the release of pro-apoptotic proteins from the mitochondria, leading to the activation of caspase-dependent and independent apoptosis. However, it has recently become apparent that proteins involved in apoptosis also exhibit non-cell death-related physiological functions that are related to the cell cycle, differentiation, metabolism, inflammation or immunity. Such non-conventional activities were predominantly reported in non-cancer cells although, recently, such a dual function for pro-apoptotic proteins has also been reported in cancers where they are overexpressed. Interestingly, some apoptotic proteins translocate to the nucleus in order to perform a non-apoptotic function. In this review, we summarize the unconventional roles of the apoptotic proteins from a functional perspective, while focusing on two mitochondrial proteins: VDAC1 and SMAC/Diablo. Despite having pro-apoptotic functions, these proteins are overexpressed in cancers and this apparent paradox and the associated pathophysiological implications will be discussed. We will also present possible mechanisms underlying the switch from apoptotic to non-apoptotic activities although a deeper investigation into the process awaits further study.


Reduced anxiety-- and depression-like behaviors in Emx1 homozygous mutant mice.
Emx1 is a mammalian homolog of the Drosophila gap gene empty spiracles (ems). Although it has been implicated in the formation of the mouse forebrain, the neuronal functions of this homeobox gene remain unknown. The restricted expression of Emx1 to the cerebral cortex and hippocampus suggests that it might play a role in emotional and other behavioral processes. The present study examined the phenotypes of Emx1-deficient mice generated by gene targeting technology in a battery of behavioral tests with a fixed inter-trial interval of 7 days. Compared with their wild-type littermates, the Emx1 homozygous mutant mice displayed markedly lowered anxiety-like behaviors in the elevated plus maze and dark/light exploration tests. Moreover, they exhibited less depressive-like response as indicated by the reduced duration of immobility in the forced swimming paradigm. There was a trend toward reduction in prepulse inhibition of acoustic startle in the homozygotes. No significant alterations in locomotor activity and susceptibility to pentylenetetrazol-induced seizure were found. This behavioral profile indicates an involvement of Emx1 in the emotional responses of mice.


Assessing the potentials of two local topical ointments as affordable treatment against tungiasis infestation: A self-experimentation in Igbokoda, Nigeria.
Infestations caused by penetration of Tunga penetrans (Siphonaptera: Hectopsyllidae) in cutaneous sub-layers present morbidities and resulting mortalities if surgical treatment remains the obtainable. Considering the neglected nature of this infestation and the absence of marketable product, we report an observation on the use of grounded naphthalene in kerosene ointment, and powder of Piper guineense in coconut oil ointment as affordable treatment of embedded tungiasis flea in Igbokoda. A total of 80 individuals partitioned into two groups of 40 individuals each were assigned the locally made topical ointment irrespective of stages of tungiasis lesions. The mean of stage I, II and III tungiasis lesions treated with grounded naphthalene in kerosene ointment respectively decreased from 1.83, 3.42 and 3.89 to 0 after 5-6 days (p < .05). Also, the mean of stage I, II and III tungiasis lesions treated with grounded P. guineense ointment respectively decreased from 1.52, 3.10 and 5.00 to 0 after 6 to 7 days of treatment exposure (p < .05). Very high significant difference between stages and exposure days of participants assigned the two topical ointment was recorded p < .0001 and p = .0005 respectively. Naphthalene ointment and to a lesser extent P. guineense ointment is best to control and hinder development cycle of embedded fleas irrespective of infested part and stage of infection.


Migration of lymphoblasts to the small intestine. III. Strain differences and relationship to distribution and duration of Trichinella spiralis infection.
In NIH strain mice, in which the majority of Trichinella spiralis are located in the anterior half of the small intestine early in the enteral phase of infection, enhanced localization of mesenteric lymphoblasts, nylon wool separated mesenteric T-lymphoblasts and even oxazolone sensitized peripheral lymphoblasts is most prominent in the anterior region of the small intestine. As the worms move to the posterior half of the small intestine, enahnced localization of lymphoblasts is observed in that region only. In BALB/c mice, in which most of the worms are located in the posterior half of the small intestine, enhanced localization of lymphoblasts is primarily in that region. Expulsion of the worms commences within 2--3 days of a large increase in the number of lymphoblasts localizing in the anterior region of the small intestine in NIH strain mice and likewise follows a second and larger increase in the number of lymphoblasts localizing in the posterior region of the small intestine of BALB/c mice.


Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome: a case report.
At 20 weeks of gestation, a typical combination of a massive enlargement of the right fetal leg and multiple cystic lesions was detected at ultrasound examination. Color-coded Doppler examination revealed no arteriovenous fistulae. These findings allowed an in utero diagnosis of the Klippel-Trenaunay-Weber syndrome, which was confirmed after subsequent termination of the pregnancy. The severe malformation involved the upper and lower right leg. No arteriovenous fistulae were found.


Effect of nitroglycerin on spinal cord ischemia after thoracic aortic cross-clamping.
Thoracic aortic cross-clamping with the use of sodium nitroprusside (SNP) has been shown to cause a decrease in spinal cord perfusion pressure and an increased incidence of paraplegia. Nitroglycerin is frequently used in this setting. This study investigated the effects of nitroglycerin and SNP on spinal cord ischemia. Three-groups of 8 mongrel dogs underwent thoracic aortic cross-clamping for 45 minutes. Proximal pressure was maintained between 95 and 100 mm Hg with SNP, nitroglycerin, or phlebotomy. All animals were neurologically evaluated 24 hours later by a blinded observer, and the findings were confirmed by histopathologic study. Statistical analysis (p value of less than 0.05) of measured hemodynamic data was by analysis of variance and of Tarlov scores, the Mann-Whitney U test. Distal aortic pressures (p < 0.001), Tarlov scores, and spinal cord perfusion pressures (p < 0.01 and p < 0.05 for SNP group and nitroglycerin group, respectively) were significantly higher in the phlebotomy group compared with the SNP and NTG groups. Cerebrospinal fluid pressures were significantly lower in the phlebotomy group compared with the SNP group (p < 0.001). The use of either NTG or SNP was associated with a high incidence of paraplegia. Nitroglycerin appears to be no safer than SNP when used during thoracic aortic cross-clamping.


Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study.
The aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care unit (ICU). This was a multicenter, randomized, double-blinded, fentanyl-controlled, non-inferiority phase 3 study. Patients aged ≥ 20 years requiring 6 h to 10 days mechanical ventilation in an ICU and requiring pain relief were randomly assigned in a 1:1 ratio to receive either remifentanil (n = 98) or fentanyl (n = 98). Dose was titrated from an infusion rate of 1 mL/h (remifentanil: 0.025 µg/kg/min, fentanyl: 0.1 µg/kg/h) until the target level of analgesia (behavioral pain scale [BPS] ≤ 5 or numerical rating score [NRS] ≤ 3) was achieved by escalating the dose in 1 mL/h increasing. Administration was then adjusted to maintain the target level of analgesia until weaning from the ventilator. The primary endpoint was the proportion of patients who did not require rescue fentanyl. Safety was assessed according to standard procedures. PK of remifentanil in the arterial blood was assessed in 24 patients. The proportion of patients achieving the primary endpoint in the remifentanil and fentanyl groups was 100% (92/92) and 97.8% (88/90), respectively. The difference between the groups was 2.2% (95% confidence interval, - 0.8-5.3) and non-inferiority of remifentanil to fentanyl was verified (p < 0.0001). The incidences of any adverse events in the remifentanil and fentanyl groups was 34 of 92 patients (37.0%) and 34 of 90 patients (37.8%), respectively. Adverse drug reactions was 12 in 92 patients (13.0%) and 15 in 90 patients (16.7%), respectively. In the PK analysis, blood remifentanil concentration decreased within 10 min to almost 50% of the end of administration, suggesting rapid offset of action following discontinuation of remifentanil. Remifentanil can be used safely for pain management in mechanically ventilated Japanese patients in the ICU. Japan Registry of Clinical Trials, jRCT2080224954. Registered 20 November 2019, https://jrct.niph.go.jp/latest-detail/jRCT2080224954 .


Ag3PO4-based photocatalysts and their application in organic-polluted wastewater treatment.
Semiconductor photocatalysis technology has shown great potential in the field of organic pollutant removal, as it can use clean and pollution-free solar energy as driving force. The discovery of silver phosphate (Ag3PO4) is a major breakthrough in the field of visible light responsive semiconductor photocatalysis due to its robust capacity to absorb visible light < 520 nm. Furthermore, the holes produced in Ag3PO4 under light excitation possess a strong oxidation ability. However, the strong oxidation activity of Ag3PO4 is only achieved in the presence of electron sacrifice agents. Otherwise, photocorrosion would greatly reduce the reuse efficiency of Ag3PO4. This review thus focuses on the structural characteristics and preparation methods of Ag3PO4. Particularly, the recent advances in noble metal deposition, ion doping, and semiconductor coupling, as well as methods of magnetic composite modification for the improvement of catalytic activity and recycling efficiency of Ag3PO4-based catalysts, were also discussed, and all of these measures could enhance the catalytic performance of Ag3PO4 toward organic pollutants degradation. Additionally, some potential modification methods for Ag3PO4 were also proposed. This review thus provides insights into the advantages and disadvantages of the application of Ag3PO4 in the field of photocatalysis, clarifies the photocorrosion essence of Ag3PO4, and reveals the means to improve photocatalytic activity and stability of Ag3PO4. Furthermore, it provides a theoretical and methodological basis for studying Ag3PO4-based photocatalyst and also compiles valuable information regarding the photocatalytic treatment of organic polluted wastewater.


Researchers highlight possible toxicology effects of nano-alumina.
Scientists have investigated whether nanoparticulate aluminum oxide can cause neurobehavioral defects in mice


Factors impacting hospital avoidance program utilisation in the care of acutely unwell residential aged care facility residents.
An existing hospital avoidance program, the Aged Care Rapid Response Team (ARRT), rapidly delivers geriatric outreach services to acutely unwell or older people with declining health at risk of hospitalisation. The aim of the current study was to explore health professionals' perspectives on the factors impacting ARRT utilisation in the care of acutely unwell residential aged care facility residents. Semi-structured interviews were conducted with two Geriatricians, two ARRT Clinical Nurse Consultants, an ED-based Clinical Nurse Specialist, and an Extended Care Paramedic. Interview questions elicited views on key factors regarding care decisions and care transitions for acutely unwell residential aged care facility residents. Thematic analysis was undertaken to identify themes and sub-themes from interviews. Analysis of interviews identified five overarching themes affecting ARRT utilisation in the care of acutely unwell residents: (1) resident care needs; (2) family factors; (3) enabling factors; (4) barriers; and (5) adaptability and responsiveness to the COVID-19 pandemic. Various factors impact on hospital avoidance program utilisation in the care of acutely unwell older aged care facility residents. This information provides additional context to existing quantitative evaluations of hospital avoidance programs, as well as informing the design of future hospital avoidance programs.


Transgenic potato overproducing L-ascorbic acid resisted an increase in methylglyoxal under salinity stress via maintaining higher reduced glutathione level and glyoxalase enzyme activity.
Salt-tolerance was studied in transgenic potato. It was conferred by overexpression of ascorbate pathway enzyme (D-galacturonic acid reductase, GalUR). As genetic engineering of the GalUR gene in potato enhances its ascorbic acid content (L-AsA), and subsequently plants suffered minimal oxidative stress-induced damage, we now report on the comprehensive aptness of this engineering approach for enhanced salt tolerance in transgenic potato (Solanum tuberosum L. cv. Taedong Valley). Potatoes overexpressing GalUR grew and tuberized in continuous presence of 200 mM of NaCl. The transgenic plants maintained a higher reduced to oxidized glutathione (GSH:GSSG) ratio together with enhanced activity of glutathione dependent antioxidative and glyoxalase enzymes under salinity stress. The transgenics resisted an increase in methylglyoxal that increased radically in untransformed control plants under salinity stress. This is the first report of genetic engineering of ascorbate pathway gene in maintaining higher level of GSH homeostasis along with higher glyoxalase activity inhibiting the accumulation in methylglyoxal (a potent cytotoxic compound) under salt stress. These results suggested the engineering of ascorbate pathway enzymes as a major step towards developing salinity tolerant crop plants.


[Clinical variability of bilateral paramedian thalamic infarcts].
Thalamic infarcts in paramedian artery territory are seen fairly frequently owing to certain peculiarities of the vascularization of the thalamus. However, clinical diagnosis is usually difficult because of the many varieties and peculiarities of the symptomatology. We present a review of twelve cases of bilateral paramedian infarcts of the thalamus seen in our Department of Neurology and in a private surgery. We analyze the symptoms and their relationship to the neuro-radiological findings. Finally we compare our observations with the descriptions published by other authors and seek and anatomo-functional relationship for each of the symptoms and signs observed. The usual clinical outline in our patients included disorders of consciousness, different types of oculomotor disorders and cerebellar symptoms, mainly of gait. Other less common findings were memory disorders and abnormal movements. In no case were there sensory changes and pyramidal signs were rare in the absence of significant extra-thalamic lesions. Our findings, although generally comparable to those described in the literature consulted, were somewhat different with regard to cerebellar symptoms and the absence of sensory and pyramidal signs. We also emphasize the marked differences seen between the individual patients in our series. A good knowledge of the possible clinical variants of these lesions is necessary for a correct initial diagnostic approach in the study of these patients.


Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation.
The driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined. Retrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a "passive-like" decrease followed by plateau, a pattern with "clear plateau," and an "irregular rise" pattern, which included all cases of late or continuous increase, with or without plateau. Data from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively. The pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.


Fire investigation and ignitable liquid residue analysis--a review: 2001-2007.
Next to natural disasters fires cause some of the greatest losses to property and human life around the world. Arson, the deliberate setting of a fire to destroy property or to take a human life, is one of the most difficult crimes to investigate because much of the evidence at the scene is destroyed by the fire. Fortunately, the science of fire investigation is not static and more information to help investigators determine the origin and cause of a fire through careful examination of the scene and laboratory analysis of fire debris is published every year. This review article provides an overview of the scientific literature describing research and best practices in the fields of fire scene investigation as well as ignitable liquid residue analysis. This review is a compilation of articles published between late 2001 and early 2007. Conference proceedings for which full papers have not been published were intentionally excluded from this review. Some of the information contained in this review was presented at the 14th Interpol Forensic Science Symposium held in Lyon, France in October 2004.


Reply to the 'Comment on "Microflow in a rhythmically expanding alveolar chip with dynamic similarity"' by A. Tsuda and F. S. Henry, Lab Chip, 2021, 21, DOI.
This article provides our response to a comment on our article published in Lab on a Chip (H. Lv, J. Dong, Y. Qiu, Y. Yang and Y. Zhu, Lab Chip, 2020, 20, 2394-2402) by Tsuda and Henry, Lab Chip, 2020.


Food Shopping Frequency of Rural Tennessee Adults With Comparisons by Federal Nutrition Assistance Participation.
To describe food shopping frequency across 7 store types in a rural context and compare food shopping frequency between federal nutrition assistance recipients and nonrecipients. This cross-sectional study was conducted at county fairs in rural Tennessee. Reported overall mean food shopping frequency was 18.4 (SD, 13.9) times in the past 30 days. A mean of 3.1 (SD, 1.2) store types were visited, with supermarkets, convenience stores, and dollar stores the most frequented stores. Federal nutrition assistance program recipients shopped significantly less frequently than nonrecipients for overall shopping frequency (P = 0.02), supermarkets (P = 0.02), and farmers' markets (P = 0.04). Educating and counseling individuals on how food shopping frequency may promote nutrition and health may be important. Federal nutrition assistance programs that distribute benefits monthly may impact food shopping frequency.


Application of additional anthropometric and functional methods in children undergoing orthodontic treatment using braces.
Occlusal interference causes instability in temporomandibular joint and hyperactivity of mastication muscles which eventually leads to temporomandibular joint dysfunction. Therefore, achieving stable occlusion is important in young patients. It is key factor in optimizing functional occlusion in adulthood. Application of «The ABO Model Grading System» and Mandibular Position Indicator as an additional diagnostic method in children undergoing orthodontic treatment using braces. Thirty-two patients aged 14 to 18 diagnosed with teeth crowding on the upper and lower jaws were examined, then separated in two groups of 16 people each. All patients underwent orthodontic treatment using braces. In group 2, due to application the anthropometrical system of quantitative evaluation ABO with re-fixing the incorrectly arranged braces by indirect bonding method, occlusal interferences were eliminated. MPI analysis showed discrepancy between the central occlusion and the central relation which was not as relevant as in the group 1 (p > 0.05). Using the anthropometric system of quantitative assessment of ABO with subsequent re-fixation of incorrectly placed braces by indirect bonding, effectively improves the MPI. This determines the unity of position between articular condyles on the lower jaw in the centric occlusion and in the centric relation, which allows to get a stable result of orthodontic treatment.


The amino acid sequence of the gamma-subunit of mouse submaxillary gland 7 S nerve growth factor.
The complete amino acid sequence of the gamma-subunit of mouse submaxillary gland 7 S nerve growth factor has been determined from analyses of the peptides generated by cyanogen bromide, trypsin, and chymotrypsin from the naturally occurring fragments. All peptides were sequenced automatically in a spinning-cup sequenator using Polybrene to minimize extractive losses by the solvents employed thoughout the degradation cycles. The gamma-subunit, a serine protease with arginine specificity, contains 233 amino acid residues and shares sequence homology with other proteases of this family. The five disulfide bonds of the gamma-subunit are a subset of the six disulfides present in bovine trypsin, as judged by the location of the half-cystine residues in the primary structure. An N-linked carbohydrate side chain is attached to Asn-78 in at least a majority of tee gamma-molecules.


Bile acids decrease hepatic paraoxonase 1 expression and plasma high-density lipoprotein levels via FXR-mediated signaling of FGFR4.
The purpose of this research was to determine how dietary bile acids repress hepatic expression of paraoxonase 1 (PON1). C57BL/6 mice and C3H/HeJ mice, having different susceptibilities to atherosclerosis, were fed a chow diet and an atherogenic diet containing taurocholate. Compared with the more atherosclerosis-susceptible C57BL/6 mice, C3H/HeJ mice display resistance to dietary bile acid repression of hepatic PON1 mRNA and decreased high-density lipoprotein cholesterol. Whereas knockout of toll receptor 4 did not affect response to taurocholate, deletion of either FXR or FGFR4 blocked taurocholate repression of PON1 and CYP7A1. FGF19, an activator of FGFR4 expressed in human ileum, decreased expression of both PON1 and CYP7A1 expression by human hepatoma cells. In all of the mice studied, dietary taurocholate increased ileal expression of FGF15, a FXR-inducible murine homologue of human FGF19. Hepatic PON1 and CYP7A1 mRNA expression is repressed by bile acids via FXR-mediated induction of FGF15. Thus, the inability of C3H/HeJ mice to display taurocholate repression of PON1 and CYP7A1 mRNAs was not because of a lack of induction of FGF15 but rather signaling events distal to FGF15-FGFR4 association.


Production performance, egg quality and some blood parameters of heat-stressed laying hens as affected by dietary supplemental Vit B6, Mg and Zn.
The effects of dietary supplements, including magnesium sulfate (Mg), zinc oxide (Zn) and vitamin B6 (Vit B6), on the performance of laying hens reared under normal (NC) and heat-stress (HSC) conditions were investigated. A total of 288 30-week-old Lohmann LSL-Lite laying hens were randomly divided into 48 cages and assigned to receive one of the eight diets with six replicates and six hens per replicate, based on a 2 × 2 × 2 factorial arrangement of treatments. Dietary supplements, including two levels (0 & 600 mg/kg) of Mg, two levels (0 & 30 mg/kg) of Zn and two levels (0 & 8 mg/kg) of Vit B6, in normal and heat-stress conditions, were tested at 30-40 and 41-45 weeks of age, respectively. In the Vit B6 group, a decrease in feed intake (FI), egg production (EP), albumin, Zn, Fe and Mg, and an increase in triglyceride and insulin in HSC were observed, in addition to a decrease in cholesterol and an increase in egg weight (EW) in NC. Supplemental Mg decreased EP, blood triglycerides and copper in NC, and Zn, Fe and Mg in HSC as well. Feeding Zn, increased egg shape index, total protein and copper in addition to yolk index in NC and Fe in HSC. EWs were higher in hens supplemented with Vit B6+Mg in HSC. Increased insulin and decreased glutathione peroxidase activity were detected with the Vit B6+Zn compared to feeding either Vit B6 or Zn in HSC. The results indicated Vit B6 could improve EWs and suppress blood cholesterol in NC. Zn improved the egg shape index in NC.


Breaking the sound barrier: exploring parents' decision-making process of cochlear implants for their children.
To understand the dynamic experiences of parents undergoing the decision-making process regarding cochlear implants for their child(ren). Thirty-three parents of d/Deaf children participated in semi-structured interviews. Interviews were digitally recorded, transcribed, and coded using iterative and thematic coding. The results from this study reveal four salient topics related to parents' decision-making process regarding cochlear implantation: 1) factors parents considered when making the decision to get the cochlear implant for their child (e.g., desire to acculturate child into one community), 2) the extent to which parents' communities influence their decision-making (e.g., norms), 3) information sources parents seek and value when decision-making (e.g., parents value other parent's experiences the most compared to medical or online sources), and 4) personal experiences with stigma affecting their decision to not get the cochlear implant for their child. This study provides insights into values and perspectives that can be utilized to improve informed decision-making, when making risky medical decisions with long-term implications. With thorough information provisions, delineation of addressing parents' concerns and encompassing all aspects of the decision (i.e., medical, social and cultural), health professional teams could reduce the uncertainty and anxiety for parents in this decision-making process for cochlear implantation.


[Predictors of functional decline of older persons after an hospitalisation in an acute care for elder unit: importance of recent functional evolution].
To identify the predictors of functional decline of older persons after hospitalization in an Acute Care for Elder unit (ACE). Retrospective observational study based on a population hospitalised in ACE unit in Grenoble University Hospital. Dead patients within hospitalisation and patient fully disable or already hospitalized 15 days before hospitalisation were excluded. The primary outcome was the functional decline defined by a loss in activity daily life (ADL) between discharge and 15 days before hospitalisation. The predictive factors included socio-demographic data, geriatric assessment and the admission pathway. 184 patients were included (mean 86.4±6.2 years, 64.1% women). The admission by emergency department was predominant (77.2%). The mean length of stay was 16.0±9.5 days. A functional decline as present for 31.0% des patients; for 95% of these patients, the functional decline occurred before admission to ACE. Factors associated with functional decline at discharge were: recent functional decline, ADL level at admission, pressure sore, denutrition and admission via the emergency room (ER) (p<0.05). In the multivariate analysis, recent functional decline was strongly associated with functional decline at discharge (OR=58.8, p<0.01). Outside this factor, ADL level at admission (OR=3.2, p<0.01), hypoalbuminemaia (OR=2.6, p=0.01) and an admission via the ER (OR=2.6, p=0.05) were independently associated with functional decline at discharge. Better management of hospitalised older persons, according to the ACE model, has diminished the negative functional effects of hospitalization. Identification of recent functional decline rather than other usually identified predictors would be useful for detection of older patients who might benefit from a geriatric program. Detecting and correcting early malnutrition and developing direct admissions mechanisms may improve functional prognosis of hospitalised older patients.


Characterization of rat uterine estrogen receptors in vivo.
In vivo binding of [3H]estradiol ([3H]E2) in the rat uterus was performed by an intraluminal perfusion of the ligand for different time periods. In this way the binding takes place in the intact organ before processing the tissue. In 10 min, with 10 nM [3H]E2 apparent saturation or steady state incorporation of the [3H]E2 was achieved with a similar distribution of the label between cytosol and nuclear fractions. In vitro, the subcellular localization of the estrogen receptor (ER) is influenced by the extent of tissue damage. With the intact organ the ER subcellular distribution approaches that of the in vivo perfusion. With increasing [3H]E2 in the perfusate it was possible to obtain a "saturation" curve and to derive the kinetic parameters. For cytosol: Kd 16 nM; Bmax 235 fmol/mg prot. For nucleus: Kd 2.7 nM; Bmax 103 fmol/mg prot. To follow the time course of the ER movement in vivo, "pulse and wait" experiments were designed. Both uterine horns were perfused for 1 min. One of the horns was immediately processed (0 time) and the other was left in place after the perfusion for different periods. At 0 time 90% of the bound label appeared in the cytosol. At 5, 15 and 30 min, the label in the cytosol decreased and that of the nucleus increased approx. to 50%. Thus, translocation of the bound label from cytosol to nucleus was apparent. The role of the cytoplasm-nucleus ER traffic in the regulation of gene transcription by estrogens is discussed.


Tularemia outbreak, Bulgaria, 1997-2005.
The 1997-2005 tularemia outbreak in Bulgaria affected 285 people. Ten strains were isolated from humans, a tick, a hare, and water. Amplified fragment length polymorphism typing of the present isolates and of the strain isolated in 1962 suggests that a new genetic variant caused the outbreak.


Influence of CoreValve ReValving System implantation on mitral valve function: an echocardiographic study in selected patients.
The purpose of this study is to verify whether transcatheter aortic valve implantation (TAVI) determined changes in mitral valve (MV) function, in terms of mitral regurgitation (MR) and stenosis. Little data is available regarding the effects of TAVI on global MV function, often derived from analysis primarily focused on clinical and aortic related outcomes. From May 2008 to March 2010, 73 patients with severe symptomatic aortic stenosis underwent TAVI with the CoreValve ReValving System. The study population consisted of 58 patients (27 males, mean age 82 ± 7 years) who underwent transthoracic echocardiography at least ≥1 month after implantation (mean follow-up 7.8 ± 5.4 months). In patients with a left ventricular dysfunction (ejection fraction, EF, <45%) at the baseline, EF significantly increased from 37 ± 6% to 48 ± 7% after TAVI (P = 0.003). Before TAVI, 42 patients had no or mild MR, 13 mild-to-moderate, and 3 moderate or moderate-to-severe. During follow-up, the MR degree was unchanged in the majority of patients (55%), 12% reduced, and 33% worsened. Variables associated with worsening in MR were depth of aortic prosthesis (P = 0.02 for the distance between the ventricular end and the right coronary cusp; P = 0.04 for mean distance right-left coronary cusps) and left atrium area at the baseline (P = 0.02). After TAVI, six patients (10%) developed mild or moderate mitral stenosis, often in a native valve with anterior calcifications. In the majority of patients no significant changes occurred in the degree of MR in native valve, but we found that if the aortic valve was deeply implanted in the left ventricle outflow tract, a worsening in MR can be observed. A mitral stenosis development must be sought in patients with heavy calcifications of the anterior leaflet.


[Alcohol in social media: Where is the space for prevention?]
Alcohol has an almost ubiquitous presence, both offline and online. This paper therefore aims to describe the status quo of alcohol prevention on leading social media platforms in German-speaking countries. To this end, the international state of research on alcohol communication in social media is first summarized by means of a narrative review. Social media analysis is then conducted to evaluate which German-language alcohol channels reach large numbers on platforms such as Facebook and Instagram. Next, content analysis is used to examine N = 470 posts and N = 3015 user comments from the alcohol prevention social media channel with the largest reach. Finally, an online survey of N = 1150 youth (aged 16-20) explores their alcohol-related social media use. According to the state of research, communications glorifying alcohol consumption are frequently seen on social media. On leading social media platforms, the German-language alcohol channels with the widest reach are devoted to marketing and humor; prevention is significantly less prevalent. To date, the social media channel with the highest reach for alcohol prevention is the Facebook page of the BZgA youth campaign "Alcohol? Kenn dein Limit," which achieves the highest interaction rates through videos and user polls. Here, young social media users both express criticism of alcohol consumption (11% of comments) and continue to favor it (21%). Around half of the surveyed young people have already participated in alcohol-related online communication. Alcohol prevention faces the task of countering the glorification of alcohol that dominates social media with sensitizing messages.


Selective C-O Bond Forming Reactions at Indole-C2-Position toward Polycyclic Indolone or Indolinone Derivatives Tethered with Medium-Sized Rings.
A methodology involving the chemoselective synthesis of tetracyclic [1,3]oxazino[3,2-a]indol-4-one or tetracyclic [1,3]oxazino[3,2-a]indoline-4-one tethered with a medium-sized ring by cross dehydrogenative coupling (CDC) or nucleophilic addition (NA) reaction has been developed. [1,3]Oxazino[3,2-a]indol-4-one compounds fused with a medium-sized ring were constructed through a CDC reaction in the presence of I2 and K2CO3. Whereas, [1,3]oxazino[3,2-a]indoline-4-ones tethered with a medium-sized ring were obtained with a TfOH system by NA reaction.


Time-domain T-wave alternans measured from Holter electrocardiograms predicts cardiac mortality in patients with left ventricular dysfunction: a prospective study.
Time-domain T-wave alternans (TWA) is useful for identifying patients at risk for serious events after myocardial infarction. The purpose of this study was to prospectively evaluate the utility of time-domain TWA measured from Holter ECGs in predicting cardiac mortality in patients with left ventricular (LV) dysfunction. Two hundred ninety-five consecutive patients with LV dysfunction were enrolled in the study. Patients were divided into two groups: the ischemic group (n = 195) and the nonischemic group (n = 100). Time-domain TWA was assessed using the modified moving average method from routine 24-hour Holter ECGs recorded during daily activity. The maximal time-domain TWA voltage at heart rate <or=120 bpm in either lead V(5) or V(1) was derived and its value defined as positive when the voltage was >or=65 microV. The primary end-point was defined as cardiac mortality. Mean maximal time-domain TWA voltage was 54 +/- 16 microV. During follow-up of 390 +/- 212 days, 27 patients (17 in the ischemic group and 10 in the nonischemic group) died of cardiac causes. Fifty-three patients (18%) were time-domain TWA positive and 242 (82%) were time-domain TWA negative. Univariate Cox proportional hazards analyses revealed that older age, New York Heart Association functional class III or IV, diabetes, renal dysfunction, nonsustained ventricular tachycardia, and time-domain TWA were associated with cardiac mortality. In multivariate analysis, time-domain TWA had the most significant value (hazard ratio = 17.1, P <.0001). This index also was significant in both subgroups (ischemic group: hazard ratio = 19.0, P <.0001; nonischemic group: hazard ratio = 12.3, P = .002). Time-domain TWA measured from 24-hour Holter ECGs predicts cardiac mortality in patients with ischemic and nonischemic LV dysfunction.


Generating a Wnt switch: it's all about the right dosage.
Wnt proteins can activate different branches of the Wnt signaling pathway, raising the question of specificity. In this issue, Nalesso et al. (2011. J. Cell Biol. doi:10.1083/jcb.201011051) provide an answer to this conundrum by showing that different concentrations of Wnt ligands can elicit different intracellular responses. These findings not only provide new insights into the molecular mechanisms underlying Wnt signaling, but also indicate how Wnt gradients might contribute to tissue patterning during embryogenesis.


Innervation of intrapulmonary airway smooth muscle of the dog, monkey and baboon.
Intrapulmonary airways of the dog, monkey and baboon were examined with the electron microscope. Differentiation of adrenergic and nonadrenergic nerves was facilitated by the use of 5-hydroxydopamine which was infused into the pulmonary arteries (500 microgram/min for 30-45 min). In all species, nerves composed mainly of unmyelinated axons lay external to the muscularis and in the muscularis between bundles of smooth muscle cells. Nerves composed of varicose unmyelinated axons that ran parallel with the smooth muscle bundles contributed fibers that surrounded and entered these bundles. Most of the varicosities associated with airway smooth muscle were cholinergic, and longitudinal sections of the muscle bundles revealed elongate profiles of these varicosities. Most cholinergic varicosities in dog, monkey and baboon airway smooth muscle had no special morphologic relationships to the surrounding smooth muscle cells. Other cholinergic varicosities in the primates lay in depressions of the sarcolemmae. Some of these varicosities were apposed to the sarcolemmae and formed neuromuscular clefts devoid of electron-dense material. There were some adrenergic varicosities near bronchial smooth muscle cells of all species studied. Another type of nerve varicosity, which was present in all species contained many large dense-core vesicles 90-120 nm in diameter and some small, agranular vesicles 40-60 nm in diameter.


Family and genetic association studies of bipolar disorder in children.
The risk of bipolar disorder (BPD) (15-42%) in first-degree relatives of children with BPD are consistently larger than the 8.7% estimate of recurrence risk of BPD in first-degree relatives of adult BPD cases. There have been no family linkage studies of pediatric BPD, but secondary analyses of adult linkage samples suggest that early-onset BPD both increases the strength of associations in linkage studies. Positive associations with pediatric BPD and the BDNF gene (Vall66), the GAD1 gene (4s2241165), and the dopamine transporter gene (rs41084) have been reported but none of these associations have been replicated in independent samples. The number of informative families examined so far is quite small and studies were vastly underpowered to detect small effects. An adequately powered sample will likely require collaborative ascertainment of cases and families from multiple sites using valid and accepted measures of pediatric BPD.


Short stature and failure of pubertal development in thalassaemia major: evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion.
In patients with beta-thalassaemia major, frequent blood transfusions combined with desferrioxamine chelation therapy lead to an improved rate of survival. Endocrine disorders related to secondary haemosiderosis such as short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. A total of 32 patients with beta-thalassaemia major undergoing treatment at the Children's Hospital, University of Göttingen were examined. Fourteen of these were short in stature. Growth hormone (GH) secretion was investigated in 13 patients exhibiting either a short stature or reduced growth rate. The stimulated GH secretion of 10 patients in this subgroup lay within the normal range. Studies of their spontaneous GH secretion during the night revealed that these patients had a markedly reduced mean GH and reduced amplitudes in their GH peaks. Low insulin-like growth factor (IGF)-I levels were seen in the growth-retarded thalassaemic patients. Eight were subjected to an IGF generation test and showed a strong increase in both IGF-I and insulin-like growth factor binding protein (IGFBP)-3 levels indicating intact IGF-I generation by the liver. Hypogonadotropic hypogonadism was found to be present in both the male and female patients with impaired sexual development. After priming with LH-releasing hormone (GnRH) per pump in 2 female and 5 male patients, no change in either their serum oestradiol or testosterone levels or in LH/FSH response to GnRH was observed suggesting that they were suffering from a severe pituitary gonadotropin insufficiency. Three male patients at the age of puberty but exhibiting short stature. low GH, low IGF-I and hypogonadism received low dose long-acting testosterone. After 3 12 months of therapy there was a marked growth spurt, higher nocturnal GH levels and an increase in both IGF-I and IGFBP-3. Reduced GH secretion and low IGF-I in thalassaemic patients are related to a neurosecretory dysfunction due to iron overload rather than to liver damage. Hypogonadotropic hypogonadism is caused by the selective loss of pituitary gonadotropin function. In patients with both GH deficiency and hypogonadism, low dose sexual steroid treatment should be considered either as an alternative or an additional treatment before starting GH therapy.


Assessment of thyroid hormone activity of halogenated bisphenol A using a yeast two-hybrid assay.
The thyroid hormone agonist/antagonist activities of halogenated derivatives of bisphenol A (BPA) were assessed using a yeast two-hybrid assay incorporating the human thyroid hormone α (TRα), both with and without possible metabolic activation by rat liver S9 preparation. In the absence of the rat liver S9 preparation, 3,3',5,5'-tetrabromobisphenol A (TBBPA), 3,3',5,5'-tetrachlorobisphenol A (TCBPA), and 3,3',5-trichlorobisphenol A (3,3',5-triClBPA) exhibited agonist activity, whereas 3-chlorobisphenol A (3-ClBPA), 3,5-dichlorobisphenol A (3,5-diClBPA), 3,3'-dichlorobisphenol A (3,3'-diClBPA), and BPA did not. The activities of TBBPA and TCBPA increased markedly (7.6-fold and 3.1-fold, respectively) after their metabolic activation with the rat liver S9 preparation. TBBPA, TCBPA, and 3,3',5-triClBPA inhibited the binding of triiodothyronine (T3) to TRα at 2×10(-5) M without rat liver S9 treatment and 4×10(-6) M with rat liver S9 treatment, demonstrating their T3 antagonist activity. These results revealed that metabolic activation by rat liver S9 significantly increased the agonist/antagonist potential of some halogenated BPAs.