Fornix White Matter is Correlated with Resting-State Functional Connectivity of the Thalamus and Hippocampus in Healthy Aging but Not in Mild Cognitive Impairment - A Preliminary Study.
In this study, we wished to examine the relationship between the structural connectivity of the fornix, a white matter (WM) tract in the limbic system, which is affected in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease, and the resting-state functional connectivity (FC) of two key related subcortical structures, the thalamus, and hippocampus. Twenty-two older healthy controls (HC) and 18 older adults with aMCI underwent multi-modal MRI scanning. The fornix was reconstructed using constrained-spherical deconvolution-based tractography. The FC between the thalamus and hippocampus was calculated using a region-of-interest approach from which the mean time series were exacted and correlated. Diffusion tensor imaging measures of the WM microstructure of the fornix were correlated against the Fisher Z correlation values from the FC analysis. There was no difference between the groups in the fornix WM measures, nor in the resting-state FC of the thalamus and hippocampus. We did however find that the relationship between functional and structural connectivity differed significantly between the groups. In the HCs, there was a significant positive association between linear diffusion (CL) in the fornix and the FC of the thalamus and hippocampus, however, there was no relationship between these measures in the aMCI group. These preliminary findings suggest that in aMCI, the relationship between the functional and structural connectivity of regions of the limbic system may be significantly altered compared to healthy ageing. The combined use of diffusion weighted imaging and functional MRI may advance our understanding of neural network changes in aMCI, and elucidate subtle changes in the relationship between structural and functional brain networks.


[Factors determining the frequency and pathways of the parthenogenetic development of ethanol-activated mouse oocytes].
Ethanol activates the eggs inside the mother upon intraperitoneal, rather than intragastric, injection. The eggs are also activated and engaged into parthenogenetic development when the eggs or the whole oviducts with the ovulated eggs are placed in a culture medium with ethanol. The intensity of the activating effect of ethanol in vitro and ways of parthenogenetic development depend both on the ethanol concentration and temperature. At a temperature below 17 degrees ethanol did not activate the mouse eggs. There is a temperature optimum for each ethanol concentration studied (from 2 to 6.6%), at and ways of parthenogenetic development depend both on the ethanol concentration and the ability of parthenogenetic embryos to develop until the blastocyst stage are determined by the efficiency of activation and depend on the selection of optimal conditions for the action of ethanol. Cytochalasin B or D did not enhance the activating action of ethanol on the mouse eggs. The mechanisms of ethanol action on the eggs are discussed.


Post-traumatic stress disorder among heart disease patients: a clinical follow-up of individuals with myocardial infarction in the Tromsø Study.
Myocardial infarction is likely to be experienced as a life-threatening and potentially traumatic event. Approximately one-third of patients with myocardial infarction experience clinically significant symptoms of anxiety/depression. However, it is unclear how many of these patients experience these symptoms because of post-traumatic stress disorder (PTSD). We conducted a clinical screening of individuals with a confirmed myocardial infarction diagnosis. Our goal was to examine the prevalence of PTSD in myocardial infarction patients and study how PTSD symptoms were associated with exposure to potentially traumatic events. This is epidemiological research with a cross-sectional design following up participants from the Tromsø Study with a confirmed diagnosis of myocardial infarction. We sent invitations to participants in the Tromsø Study with clinically significant self-reported anxiety or depression symptoms following myocardial infarction. A cross-sectional sample of N = 79 participants (61 men and 18 women) was collected. During an interview, participants completed the Stressful Life Events Screening Questionnaire and the PTSD checklist PCL-5. We found nine participants (11.6%) with probable PTSD. This was significantly higher than the postulated population prevalence in Norway (p < 0.015). We found no direct association between myocardial infarction as illness trauma and symptom levels (p = 0.123). However, we found a significant linear trend (p = 0.002), indicating that symptom severity increased proportionately as the number of post-traumatic events increased. PTSD prevalence in myocardial infarction patients was related to lifetime exposure to traumatic events, not the myocardial infarction event alone. More research is required to examine the interaction between myocardial infarction and PTSD. Clinicians should be aware that anxiety or depression symptoms after MI could be secondary symptoms of PTSD.


Intranasal angiotensin II in humans reduces blood pressure when angiotensin II type 1 receptors are blocked.
Intranasal administration of angiotensin II (ANGII) affects blood pressure in a mode different from intravenously administered ANGII via a direct access to the brain bypassing the blood-brain barrier. This clinical study investigated blood pressure regulation after intranasal ANGII administration in healthy humans, whereas systemic, blood-mediated effects of ANGII were specifically blocked. In a balanced crossover design, men (n=8) and women (n=8) were intranasally administered ANGII (400 μg) or placebo after ANGII type 1 receptors had been blocked by pretreatment with valsartan (80 mg; 12 and 6 hours before intranasal administration). Plasma levels of ANGII, aldosterone, renin, vasopressin, and norepinephrine were measured; blood pressure and heart rate were recorded continuously. Intranasal ANGII acutely decreased blood pressure without altering the heart rate. Plasma levels of vasopressin and norepinephrine remained unaffected. Plasma ANGII levels were increased throughout the recording period. Aldosterone levels increased despite the peripheral ANGII type 1 receptor blockade, indicating an aldosterone escape phenomenon. In conclusion, intranasal ANGII reduces blood pressure in the presence of selective ANGII type 1 receptor blockade. Intranasal ANGII administration represents a useful approach for unraveling the role of this peptide in blood pressure regulation in humans.


Biosynthesized composites of Au-Ag nanoparticles using Trapa peel extract induced ROS-mediated p53 independent apoptosis in cancer cells.
The current study highlights rapid, sustainable, and cost-effective biosynthesis of silver (Ag), gold (Au) nanoparticles (NPs), and bimetallic Au-AgNPs composites using bio-waste extract of Trapa natans. Growth of the NPs was monitored spectrophotometrically and peak was observed at ∼525 nm, ∼450 nm, and ∼495 nm corresponding to Plasmon absorbance of AuNPs, AgNPs, and Au-AgNPs, respectively. Transmission electron microscopy (TEM) revealed the size of AgNPs (∼15 nm), AuNPs (∼25 nm), and Au-AgNPs (∼26-90 nm). Synthesized NPs follow the Gaussian bell curve and its crystalline nature was identified by X-ray diffraction (XRD). Furthermore, Au-AgNPs induced cytotoxicity in various cancer cells (HCT116, MDA-MB-231, and HeLa) effectively at 200 μg/mL. Au-AgNPs-exposed cancer cells exhibited apoptotic features such as nuclear condensation, mitochondrial membrane potential loss, and cleavage of casp-3 and poly (ADP-ribose) polymerase-1 (PARP). Au-AgNPs exposure enhanced reactive oxygen species (ROS) and upon inhibition of ROS, apoptosis was reduced effectively. NPs treatment killed HCT116 WT and p53 knockout cells without any significant difference. Mechanistically, Au-AgNPs derived with Trapa peel extract significantly enhance ROS which trigger p53-independent apoptosis in various cancer cells effectively. Our study explores the use of bio-waste for the green synthesis of NPs, which can be attractive candidates for cancer therapy.


The global need and availability of blood products: a modelling study.
Blood transfusions are an important resource of every health-care system, with often limited supply in low-income and middle-income countries; however, the degree of unmet need for blood transfusions is often unknown. We therefore aimed to estimate the blood transfusion need and supply at national level to determine gaps in transfusion services globally. We did a modelling study involving 195 countries and territories. We used blood component preparation data from 2011-13 to estimate blood availability for 180 (92%) of 195 countries from the WHO Global Status Report on Blood Safety and Availability. We calculated disease-specific transfusion needs per prevalent case for 20 causes in the USA using the National (Nationwide) Inpatient Sample dataset between the years 2000 and 2014, and the State Inpatient Databases between 2003 and 2007 from the Healthcare Cost and Utilization Project. Using prevalence estimates for the USA from the Global Burden of Disease (GBD) 2017 study, we estimated the ideal disease specific-transfusion rate as the lowest rate from the years 2000 to 2014. We applied this rate to GBD prevalence results for 195 countries to estimate transfusion needs. Unmet need was the difference between the estimated supply and need. In 2017, the global blood need was 304 711 244 (95% uncertainty interval [UI] 293 064 637-314 049 479) and the global blood supply was 272 270 243 (268 002 639-276 698 494) blood product units, with a need-to-supply ratio of 1·12 (95% UI 1·07-1·16). Of the 195 countries, 119 (61%) did not have sufficient blood supply to meet their need. Across these 119 countries, the unmet need totalled 102 359 632 (95% UI 93 381 710-111 360 725) blood product units, equal to 1849 (1687-2011) units per 100 000 population globally. Every country in central, eastern, and western sub-Saharan Africa, Oceania, and south Asia had insufficient blood to meet their needs. Our data suggest that the gap between need and supply is large in many low-income and middle-income countries, and reinforce that the WHO target of 10-20 donations per 1000 population is an underestimate for many countries. A continuous expansion and optimisation of national transfusion services and implementation of evidence-based strategies for blood availability is needed globally, as is more government support, financially, structurally, and through establishment of a regulatory oversight to ensure supply, quality, and safety in low-income and middle-income countries. National Institutes of Health.


Head injury and helmet usage trends for alpine skiers and snowboarders in western Canada during the decade 2008-9 to 2017-18.
This research explores snowsport head injury trends in western Canadian resorts over the decade 2008-2018. Ecological study. Head-injury and participation data on alpine skiing and snowboarding (snowsports) was provided by the Canada West Ski Areas Association (CWSAA) for 2008-2018. Injury reports from the ski patrol of 52 western Canadian resorts were analysed. 29 resorts were included where there was both injury and participation data for at least 8 out of 10 seasons, resulting in analysis of 10,371 reports. Data was imported into SPSS 24 for analysis using descriptive statistics, chi-squared analysis, odds ratios and linear regression. Over the decade: the head injury rate was 0.205 injuries per thousand skier days. Head injuries were 9-10% of all injuries, significantly lower for skiers (8.3%) than snowboarders (10.9%). There were no significant differences in helmet-usage rates of injured and non-injured populations. 80.6% of injured participants wore a helmet, those wearing a helmet were 8% more likely to report a head injury than those not wearing a helmet. There was little variation in the proportion of head injuries reported as concussion, but a 50% reduction in ambulance or helicopter transport, a head-injury severity proxy. There was a significant relationship between the proportion of snowsport participants who were snowboarders and the head-injury rate. Head injuries remain a rare event. There has been a decline in the severity of reported head injuries which may be a function of a decline in the proportion of snowboarders in snowsports.


Vasoplegic shock during liver transplantation: is the preoperative cGMP plasma level a potential predictor of hemodynamic instability?
Refractory hypotension is a frequent event during reperfusion of a liver graft. Measures that help maintain hemodynamic stability include correction of electrolytes and acid-base abnormalities as well as administration of fluid and/or catecholamines. Vasoplegic syndrome represents the most severe form of hemodynamic instability. Management of this condition is very difficult due primarily to the inadequate response to even very high doses of catecholamines. A 60-year-old patient presented for liver transplantation due to end stage liver disease. After an initially uneventful hepatic phase, the patient developed excessive tachycardia and refractory hypotension during cross-clamping of the vena cava. The situation rapidly deteriorated despite administration of fluid and extremely high doses of norepinephrine and vasopressin. A transesophageal echocardiogram (TEE) performed at that time failed to demonstrate any cardiac dysfunction or signs of pulmonary emboli. Subsequent blood cultures and imaging studies did not confirm any signs of sepsis. Further investigation revealed an increased preoperative level of cyclic guanosine monophosphate (cGMP). cGMP is the second messenger for nitric oxide, and is responsible for relaxation of vascular smooth muscle with subsequent vasodilatation. This finding suggests a release of nitric oxide in the systemic circulation which could have been a potential cause for vasoplegic shock. Release of nitric oxide in the systemic circulation can be a potential cause of vasoplegic syndrome. Future investigation will demonstrate whether a patient's preoperative cGMP plasma level can be a potential predictor of intraoperative hemodynamic instability.


Reduction in mortality from breast cancer after mass screening with mammography. Randomised trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare.
A randomised controlled trial to investigate the efficacy of mass screening with single-view mammography in reducing mortality from breast cancer was started in Sweden in 1977. 162 981 women aged 40 years or more and living in the counties of Kopparberg and Ostergötland were enrolled in the study and divided at random into 2 groups. Each woman in the study group was offered screening every 2 or 3 years depending on age. Women in the control group were not offered screening. This report is confined to the 134 867 women aged 40-74 years at date of entry. The results to the end of 1984 show a 31% reduction in mortality from breast cancer and a 25% reduction in the rate of stage II or more advanced breast cancers in the group invited to screening. 7 years after the start of the study the excess of stage I cancers in the study group largely outweighs the deficit of advanced cancers.


Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Niemann-Pick C1-like 1.
Cholesterol membrane transporters scavenger receptor class B type I (SR-BI) and (cluster determinant 36) are involved in intestinal uptake of lutein and beta-carotene, 2 of the 3 main carotenoids of the human diet. The aim of this work was therefore to determine whether SR-BI and NPC1L1 (Niemann-Pick C1-like 1), another cholesterol transporter, are implicated in absorption of lycopene, the 3rd main carotenoid of the human diet. Anti-human SR-BI antibody and block lipid transport 1 (BLT1) (a chemical inhibitor of lipid transport by SR-BI) impaired up to 60% (all-E) and (5Z)-lycopene uptake (P < 0.05) by Caco-2 cell monolayers, which were used as a model of human intestinal epithelium. The involvement of SR-BI in lycopene absorption in vivo was then verified by comparing plasma lycopene concentrations in wild-type and SR-BI transgenic mice that were fed a diet enriched with 0.25 g/kg (all-E)-lycopene for 1 mo. Plasma lycopene concentrations were approximately 10-fold higher (P < 0.001) in mice overexpressing SR-BI in the intestine than in wild-type mice, confirming the involvement of SR-BI in lycopene absorption. Further experiments showed that (all-E)-lycopene did not affect SR-BI mRNA levels in Caco-2 cells or mouse intestine. In contrast to SR-BI, neither anti-human NPC1L1 antibody nor ezetimibe, used as inhibitors of lycopene uptake via NPC1L1, significantly impaired (all-E) or (5Z)-lycopene uptake by Caco-2 monolayers. Thus, the present data show that lycopene absorption is, at least in part, mediated by SR-BI but not by NPC1L1.


Effect of grazers and viruses on bacterial community structure and production in two contrasting trophic lakes.
Over the last 30 years, extensive studies have revealed the crucial roles played by microbes in aquatic ecosystems. It has been shown that bacteria, viruses and protozoan grazers are dominant in terms of abundance and biomass. The frequent interactions between these microbiological compartments are responsible for strong trophic links from dissolved organic matter to higher trophic levels, via heterotrophic bacteria, which form the basis for the important biogeochemical roles of microbial food webs in aquatic ecosystems. To gain a better understanding of the interactions between bacteria, viruses and flagellates in lacustrine ecosystems, we investigated the effect of protistan bacterivory on bacterial abundance, production and structure [determined by 16S rRNA PCR-DGGE], and viral abundance and activity of two lakes of contrasting trophic status. Four experiments were conducted in the oligotrophic Lake Annecy and the mesotrophic Lake Bourget over two seasons (early spring vs. summer) using a fractionation approach. In situ dark vs. light incubations were performed to consider the effects of the different treatments in the presence and absence of phototrophic activity. The presence of grazers (i.e. <5-μm small eukaryotes) affected viral production positively in all experiments, and the stimulation of viral production (compared to the treatment with no eukaryotic predators) was more variable between lakes than between seasons, with the highest value having been recorded in the mesotrophic lake (+30%). Viral lysis and grazing activities acted additively to sustain high bacterial production in all experiments. Nevertheless, the stimulation of bacterial production was more variable between seasons than between lakes, with the highest values obtained in summer (+33.5% and +37.5% in Lakes Bourget and Annecy, respectively). The presence of both predators (nanoflagellates and viruses) did not seem to have a clear influence upon bacterial community structure according to the four experiments. Our results highlight the importance of a synergistic effect, i.e. the positive influence of grazers on viral activities in sustaining (directly and indirectly) bacterial production and affecting composition, in both oligotrophic and mesotrophic lakes.


Clinical significance of redundant nerve roots in patients with lumbar spinal stenosis undergoing oblique lumbar interbody fusion combined with percutaneous internal fixation.
While there have been previous studies on the surgical efficacy of patients with redundant nerve roots (RNRs), a persistent issue is that some patients continue to experience redundancy even after surgery. Furthermore, the clinical significance of RNRs remains unclear. Notably, there is a lack of research regarding RNRs within the context of oblique lumbar interbody fusion (OLIF) combined with percutaneous internal fixation. Therefore, the primary objective of this study is to investigate the correlation between RNRs and clinical outcomes following OLIF combined with percutaneous internal fixation. Eighty-seven patients diagnosed with lumbar spinal stenosis (LSS) who underwent single-segment OLIF combined with percutaneous internal fixation were categorized into three groups. Group 1 comprised patients with positive RNRs both before and after the operation. Group 2 included patients with positive RNRs preoperatively but negative RNRs postoperatively. Group 3 consisted of patients with consistently negative RNRs before and after the operation. Comprehensive patient data were collected, including operation time, intraoperative blood loss, and any recorded complications. Radiographic parameters, both pre- and post-operative, were assessed, encompassing the number of stenosis segments, disc height (DH), lumbar lordotic angle, dural sac cross-sectional area, and the placement of the fusion cage. Furthermore, the Visual Analogue Scale was applied to gauge back and leg pain, while the Oswestry Disability Index was employed to appraise daily living activities. A comparative analysis was carried out among the three patient groups. In this study, all 87 LSS patients successfully underwent surgery. Among them, 35 patients (40.2%) showed preoperative MRI assessment indicating positive RNRs. In the postoperative MRI assessment, 14 of these patients maintained positive RNRs status, and they were grouped into Group 1. The remaining 21 patients saw a transition to negative RNRs status and were included in Group 2. Among the 52 patients who had preoperative MRI assessments showing negative RNRs, their postoperative RNRs status remained negative, forming Group 3. All patients received follow-up, which ranged from 8 to 18 months, and no complications occurred during this period. In this study, the postoperative efficacy and parameters such as DH and Dural Sac CSA significantly improved compared to preoperative values for all 87 patients. Patients with preoperative RNRs had more stenosis segments, smaller dural sac CSA, and more severe symptoms. In all three groups, postoperative efficacy scores significantly improved compared to preoperative scores. Group 2 patients had their fusion cages placed more in the middle, while Group 1 patients had their fusion cages more anteriorly located. Group 2 patients exhibited greater recovery in dural sac CSA postoperatively compared to Group 1 patients. Additionally, Group 2 patients had better ODI efficacy scores compared to Group 1 patients. Irrespective of the presence or absence of RNRs, patients experienced improvement after undergoing OLIF combined with percutaneous internal fixation. Preoperative RNRs appear to be linked to multi-segmental lumbar spinal stenosis, a reduction in dural sac CSA, and symptom severity. Patients with negative postoperative RNRs demonstrated better treatment efficacy. Furthermore, the placement of the fusion cage appears to have a significant impact on postoperative efficacy and RNRs outcomes.


The Misuse of Prescription Opioids: A Threat for Europe?
In the the past two decades the medical use of prescription opioids (POs), in particular oxycodone, increased up to 14-fold in the U.S. and Canada. The high consumption of these pain relievers also led to non-medical use and abuse of these substances which in turn resulted in a dramatic increase in the number of PO related fatalities and opioid dependent subjects. In the U.S. POs became the second most prevalent type of abused drug (4.5 million abusers; 1.7% of the population) after marijuana (8 million abusers) with currently 1.9 million (0.7% of the population) people dependent on opioid pain relievers. Pain relief was the leading motive for non-medical use in about 40% of the cases, but about half of non-medical PO users reported non-pain relief motives only, like to get high or to relax. Since 2011, there is a decline in the use and misuse of POs and reduction in painkiller overdose deaths in the U.S. probably due to the introduction of a variety of restrictive regulations. In Europe, the medical use of POs is increasing as well, but at a much slower rate than in the U.S. Moreover, in Europe non-medical use of POs and fatal PO incidents are (still) rare. The paper highlights and discusses the differences between Europe versus U.S. and Canada in an attempt to assess the risk of a PO abuse and overdose epidemic in Europe. It is concluded that the risk in Europe seems to be rather limited but vigilance is needed.


The Use of Complementary and Alternative Medicine in Patients with Migraine.
Although many patients with migraine get positive benefits from conventional pharmacological treatments, many others do not benefit sufficiently or experience adverse effects from these treatments. For that reason, these patients usually seek complementary and/or alternative medical (CAM) treatments all over the world. In general, although CAM therapies are not recommended by neurologist in Turkey, most of migraine patients, who do not respond conventional medicine treatments, seek alternative therapy. Acupuncture, botulinum toxin, mind-body interventions, and nutraceutical options are the most popular treatments. In this review, the available evidence for all these treatments will be discussed.


The design and implementation of a multidisciplinary global health residency track at the Mount Sinai School of Medicine.
The Mount Sinai Global Health Center established a new multidisciplinary Global Health Residency Track (GHRT) in 2006. The goal of the GHRT is to provide participants with a foundation in global health issues and population-based health care, a chance to develop basic research and public health skills in the field, and guidance for career development. The authors describe how the GHRT was created, present its structure, and discuss their experience implementing this new program. Other selected global health residency training programs are also reviewed. The Mount Sinai GHRT is a two-year program that comprises a didactic curriculum, with participants required to take selected classes in the Master of Public Health Program of the Mount Sinai School of Medicine of New York University, and "field experience," which consists of a public health project that is implemented during a two-month elective period during the second year. Core competencies include (1) epidemiology and research skills, (2) health disparities, human rights, and cultural competency, (3) needs assessment and project development, (4) tropical medicine and infectious disease, and (5) reproductive, maternal, and child health. Nine residents were selected from four Mount Sinai residency programs to participate in the GHRT in its first year, and, during the winter of 2007, senior residents conducted public health projects in the Dominican Republic, India, Kenya, and East Harlem. All components of the track performed well in evaluations. An outcomes survey is ongoing to track career choices among graduates and to identify barriers to continuing involvement in global health.


On the cytotoxicity of HCR-NTPase in the neuroblastoma cell line SH-SY5Y.
The human cancer-related nucleoside triphosphatase (HCR-NTPase) is overexpressed in several tumour tissues including neuroblastoma. HCR-NTPase is an enzyme exhibiting a slow in vitro activity in hydrolysing nucleosidetriphosphates. However, its in vivo function is still unknown. To learn more about the physiological role of HCR-NTPase, we both overexpressed and silenced it in the neuroblastoma cell line SH-SY5Y. No effect was observed when the expression of endogenously expressed HCR-NTPase in the cells was silenced by RNA interference. On the other hand, overexpression of HCR-NTPase led to cytotoxicity of the protein in SH-SY5Y cells. Even if the catalytic essential amino acid glutamate 114 was replaced by alanine (E114A-HCR-NTPase), the protein remained cytotoxic. The results could be confirmed by successfully rescuing the cells via RNA interference. Although expressed in several tumours, at least in SH-SY5Y, HCR-NTPase is not essential for the cells to survive. Increased levels of the protein lead to cytotoxicity due to physical intracellular interactions rather than hydrolysis of nucleosidetriphosphates by its intrinsic residual enzymatic activity.


Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair.
Rigosertib is multi-kinase inhibitor that could represent an interesting therapeutic option for non-resectable patients with cholangiocarcinoma, a very aggressive hepatic cancer with limited effective treatments. The Western blotting technique was used to evaluate alterations in the expression of proteins involved in the regulation of the cell cycle of cholangiocarcinoma EGI-1 cells. Our results show an increase in EMI1 and Cyclin B protein levels after Rigosertib treatment. Moreover, the phosphorylation of CDK1 is significantly reduced by Rigosertib, while PLK1 expression increased after 24 h of treatment and decreased after 48 h. Finally, we evaluated the role of p53. Its levels increase after Rig treatment, and, as shown in the cell viability experiment with the p53 inhibitor Pifithrin, its activity is necessary for the effects of Rigosertib against the cell viability of EGI-1 cells. In conclusion, we hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. The CDK1-Cyclin B complex and p53 play an important role, explaining the Block in the G2/M phase of the cell cycle and the effect on cell viability.


[Study of physicochemical properties of lens capsule preserved under different conditions].
The role of lipid peroxidation (LPO) in the lens capsule in its preservation under different conditions is investigated. The content of LPO products (hydroperoxides and malonic dialdehyde) appreciably increased in the lens capsule after preservation in normal and Ringer's saline for 1 to 6 days at 4 degrees C. These changes were paralleled by a reliable decrease in the content of various SH groups (Superficial, structurally masked protein, and glutathion) and in catalase activity. Preservation of the lens capsule in 1% gentamicin solution almost completely prevented such changes during the first 6 days of storage. Moreover, in model systems gentamicin suppressed the intensity of Fe(2+)-ascorbate-stimulated LPO. Intensification of LPO is believed to play an appreciable role in the structural and functional disorders in the lens capsule during its storage in different media. High antioxidative activity of gentamicin recommends it as an effective preserving agent for clinical purposes.


Transformation of Epichloë typhina by electroporation of conidia.
Choke, caused by the endophytic fungus Epichloë typhina, is an important disease affecting orchardgrass (Dactylis glomerata L.) seed production in the Willamette Valley. Little is known concerning the conditions necessary for successful infection of orchardgrass by E. typhina. Detection of E. typhina in plants early in the disease cycle can be difficult due to the sparse distribution of hyphae in the plant. Therefore, a sensitive method to detect fungal infection in plants would provide an invaluable tool for elucidating the conditions for establishment of infection in orchardgrass. Utilization of a marker gene, such as the green fluorescent protein (GFP), transformed into Epichloë will facilitate characterization of the initial stages of infection and establishment of the fungus in plants. We have developed a rapid, efficient, and reproducible transformation method using electroporation of germinating Epichloë conidia isolated from infected plants. The GFP labelled E. typhina provides a valuable molecular tool to researchers studying conditions and mechanisms involved in the establishment of choke disease in orchardgrass.


Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study.
Dementia constitutes an increasingly prevalent cognitive disorder with serious socioeconomic implications. In the present study, we aimed to evaluate the efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors (ChEIs), in terms of several neuropsychological parameters, in a considerable number of patients with dementia. In our prospective, open-label study, we enrolled a total of 276 patients (mean age 71 ± 8 years, 95 males) with cognitive disorders. Our study population comprised four groups: no treatment group (n = 75), aniracetam monotherapy group (n = 58), ChEIs monotherapy group (n = 68), and group of combined treatment (n = 68). Patients were examined with validated neuropsychological tests at baseline, 3, 6, and 12 months of treatment. In patients treated with aniracetam, all studied parameters were adequately maintained at 6 and 12 months, while emotional state was significantly improved at 3 months. In patients treated with ChEIs, we observed a significant cognitive deterioration at 12 months. The comparison between aniracetam and ChEIs in patients with relatively mild dementia (15 ≤ MMSE ≤ 25) revealed a significantly better cognitive performance with aniracetam at 6 months and improved functionality at 3 months. Comparing aniracetam monotherapy with combined treatment in the same population, aniracetam performed better in the cognitive scale at 6 months, and displayed a notable tendency for enhanced mood at 12 months and improved functionality at 6 months. Our findings indicate that aniracetam (a nootropic compound with glutamatergic activity and neuroprotective potential) is a promising option for patients with cognitive deficit of mild severity. It preserved all neuropsychological parameters for at least 12 months, and seemed to exert a favorable effect on emotional stability of demented patients.


High-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in surfactant-treated rabbits with lung injury.
The aim of this study was to compare high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) with and without surfactant in the treatment of surfactant-deficient rabbits. A previously described saline lung lavage model of lung injury in adult rabbits was used. The efficacy of each therapy was assessed by evaluating gas exchange, lung deflation stability and lung histopathology. Arterial oxygenation did not improve in the CMV group without surfactant but increased rapidly to prelavage values in the other three study groups. During deflation stability, arterial oxygenation decreased to postlavage values in the group that received HFOV alone, but not in both surfactant-treated groups (HFOV and CMV). The HFOV group without surfactant showed more cellular infiltration and epithelial damage compared with both surfactant-treated groups. There was no difference in gas exchange, lung deflation stability and lung injury between HFOV and CMV after surfactant therapy. It is concluded that the use of surfactant therapy in combination with high-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in improving gas exchange, lung deflation stability and in the prevention of lung injury, if lungs are kept expanded. This indicates that achieving and maintaining alveolar expansion (i.e. open lung) is of more importance than the type of ventilator.


Prevalence and predicting factors of increased arterial stiffness in autosomal dominant polycystic kidney disease.
Carotid-femoral pulse wave velocity (cf-PWV) is the noninvasive gold standard technique for measuring aortic stiffness. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults. It is associated with a high risk of cardiovascular complications. We aimed to assess the prevalence of increased arterial stiffness and its predicting factors in a population of ADPKD patients. Sixty-two patients with ADPKD underwent noninvasive measurement of cf-PWV using a COMPLIOR Analyse device. Recruitment period was 17 months and we used the cut-off of 10 m/s to define a high cf-PWV. Mean age was 51 ± 12.7 years. Gender ratio male/female was 0.63. Smoking, hypertension (HTN), and dyslipidemia were reported in 14%, 66%, and 27% of the cases, respectively. Mean glomerular filtration rate (GFR) was 47.7 ± 44 mL/min/1.73 m2. Among our patients, 39% had chronic kidney disease stages 1 or 2 and 45% stage 5 (40% stage 5D). Mean cf-PWV was 9 ± 2.4 m/s, and 31% of the patients had a high cf-PWV. In univariate analysis of all our patients, cf- PWV correlated with age (r = 0.565; P <10-3), GFR (r = -0.268;P = 0.035), C-reactive protein (r = 0.447; P = 0.007), peripheral systolic arterial pressure (r = 0.309; P = 0.015), and peripheral pulse pressure (r = 0.335; P = 0.008). Patients with high cf-PWV were on average nine years older than the others. Patients with HTN were 3.84 times more likely to have high cf-PWV (P = 0.046). cf-PWV did not seem to be lower with any antihypertensive treatment. A level of C-reactive protein higher than 10 mg/L was the only independent predicting factor of a high cf-PWV in multivariate analysis (P = 0.043). Our study confirmed the relationship between cf-PWV and age, renal failure, and HTN in patients with ADPKD. It also emphasized the close relationship between systemic inflammation and arterial stiffness in this nephropathy.


Unilateral Papilledema in Cerebral Venous Sinus Thrombosis.
In the majority of patients with raised intracranial pressure, the papilledema is bilateral. Unilateral papilledema is rare in conditions causing intracranial hypertension, and it has been described in Foster-Kennedy syndrome and in some cases of idiopathic intracranial hypertension. It has never been reported in cerebral venous thrombosis. We report a young lady presenting with features of subacute onset of headache with seizures, on evaluation she had superior sagittal and bilateral lateral sinus thrombosis. The risk factors found on evaluation were Vitamin B12 deficiency and hyperhomocysteinemia. On optic fundus examination, she had swollen optic disc on the right side with normal fundus on the left side, confirmed with the orbital ultrasound B-scan and optic coherence tomography. Her magnetic resonance imaging showed features of raised intracranial pressure with thrombosis of the superior sagittal and bilateral lateral sinus thrombosis. She was treated with anticoagulation (heparin followed by oral anticoagulants), antiedema measures, and vitamin supplementation for hyperhomocysteinemia. She improved over time and was asymptomatic during follow-up. We discuss the possible mechanisms described in the literature for unilateral papilledema. This report highlights the need for carefully performing bilateral fundus examination so as not to miss the vision or life-threatening causes of a headache.


Potentiating cancer immunotherapy using an oncolytic virus.
Oncolytic viruses (OVs) are highly immunogenic and this limits their use in immune-competent hosts. Although immunosuppression may improve viral oncolysis, this gain is likely achieved at the cost of antitumoral immunity. We have developed a strategy wherein the immune response against the OV leads to enhanced therapeutic outcomes. We demonstrate that immunization with an adenoviral (Ad) vaccine before treatment with an oncolytic vesicular stomatitis virus (VSV) expressing the same tumor antigen (Ag) leads to significantly enhanced antitumoral immunity. Intratumoral replication of VSV was minimally attenuated in Ad-immunized hosts but extending the interval between treatments reduced the attenuating effect and further increased antitumoral immunity. More importantly, our combination approach shifted the immune response from viral Ags to tumor Ags and further reduced OV replication in normal tissues, leading to enhancements in both efficacy and safety. These studies also highlight the benefits of using a replicating, OV to boost a pre-existing antitumoral immune response as this approach generated larger responses versus tumor Ag in tumor-bearing hosts than could be achieved in tumor-free hosts. This strategy should be applicable to other vector combinations, tumor Ags, and tumor targets.


[Observations on the biology and ethology of Pipa (Hemipipa) carvalhoi Mir. RiB. 1937 (Anura, Pipidae)].
Feeding, mating behaviour, communication, breeding biology, and development of Pipa carvalhoi are described. Like in other species of the genus Pipa, the eggs are laid onto the female's back during several turnovers, and this behaviour can be observed even in the absence of males. Acoustic communication involves a mating call and a combat call. The biology and behaviour of Pipa carvalhoi are compared to that of other pipid frogs, and it is suggested that the specialized breeding biology of the genus Pipa evolved as an adaptation to the life in small ponds and ditches which are rich in nutrients but poor in oxygen.


Benchmarking the environmental performance of the Jatropha biodiesel system through a generic life cycle assessment.
In addition to available country or site-specific life cycle studies on Jatropha biodiesel we present a generic, location-independent life cycle assessment and provide a general but in-depth analysis of the environmental performance of Jatropha biodiesel for transportation. Additionally, we assess the influence of changes in byproduct use and production chain. In our assessments, we went beyond the impact on energy requirement and global warming by including impacts on ozone layer and terrestrial acidification and eutrophication. The basic Jatropha biodiesel system consumes eight times less nonrenewable energy than conventional diesel and reduces greenhouse gas emissions by 51%. This result coincides with the lower limit of the range of reduction percentages available in literature for this system and for other liquid biofuels. The impact on the ozone layer is also lower than that provoked by fossil diesel, although eutrophication and acidification increase eight times. This study investigates the general impact trends of the Jatropha system, although not considering land-use change. The results are useful as a benchmark against which other biodiesel systems can be evaluated, to calculate repayment times for land-use change induced carbon loss or as guideline with default values for assessing the environmental performance of specific variants of the system.


Genetics of Bladder Malignant Tumors in Childhood.
Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors.


Fatal bacterial endocarditis following aortic valve replacement in a patient being treated with methotrexate.
A 41-year-old man being treated with methotrexate for psoriasis underwent aortic valve replacement. He subsequently developed fulminating bacterial endocarditis. Bacterial endocarditis occurs in 1-2% of cases after prosthetic valve replacement and has a high mortality. The long-term use of methotrexate and similar drugs is increasing in conditions such as psoriasis, rheumatoid arthritis and inflammatory bowel disease. Thus, more patients undergoing heart valve surgery will be taking these preparations for coexisting disease. As methotrexate increases the risk of infection, its perioperative use in these patients requires further evaluation.


Induced Toxoplasma gondii, Toxocara canis, and Isospora canis infections in coyotes.
Six littermate laboratory-raised coyotes (No. 1-6) were used to study the transmission of Toxoplasma gondii from cats and mice, and Toxocara canis and Isospora canis from dogs and mice. Coyotes 1 and 2 were inoculated orally with 1,000 infective oocysts of the TC-1 strain of T gondii; coyotes 3 and 4 were fed mice infected with tissue cysts of the TC-1 strain of T gondii. Eight days after inoculation with T gondii, the same 4 coyotes were exposed to Toxocara canis: coyotes 1 and 2 were inoculated orally with 500 embryonated eggs, and coyotes 3 and 4 were fed mice infected with Toxocara canis. Fifteen days after exposure to Toxocara canis, the same 4 coyotes were fed mice infected with I canis. Two coyotes (No. 5 and 6) did not receive any organism and they served as controls. All 4 inoculated coyotes remained clinically normal but became infected with all 3 organisms. Toxoplasma gondii was recovered from the brain, heart, diaphragm, and muscles of limbs of coyotes killed 49 and 66 days after inoculation with oocysts, but only from muscles of limbs of coyote 4, killed at 84 days, and from the brain and muscles of limbs of coyote 3, killed at 72 days after feeding infected mice. Control coyotes did not acquire any of the 3 infections.


Antimigraine treatment for slit ventricle syndrome.
Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction; 2) intracranial hypotension; and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of "acquired" migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures.


Different Definitions of Elder Mistreatment and Mortality: A Prospective Cohort Study From 2011 to 2017.
To investigate the relationship between different definitions and subtypes of elder mistreatment (EM) and yearly mortality. Population-based epidemiological study. Greater Chicago area. Chinese Americans aged 60 and older (N=3,157). Data were collected from 2011 to 2017, with mortality data collected over the subsequent 4 years. Face-to-face in-home interviews were conducted. EM was measured using a brief screening tool (10 items) and a detailed assessment (56 items) and defined using different criteria for overall and specific subtypes of EM. Mortality was ascertained during follow-up. Cox proportional hazards models were used. Four hundred seventy-five (15.2%) participants reported EM. Severe and moderate EM were associated with greater risk of 1-year (hazard ratio (HR)=2.51, 95% confidence interval (CI)=1.04-6.03; HR=2.55, 95% CI=1.08-6.03), 2-year (HR=1.68, 95% CI=1.01-2.78; HR=1.69, 95% CI=1.04-2.74), 3-year (HR=1.73, 95% CI=1.17-2.55; HR=1.73, 95% CI=1.19-2.51) and 4-year (HR=1.51, 95% CI=1.08-2.10; HR=1.48, 95% CI=1.08-2.04) mortality. A broad definition of EM was associated with greater risk of 3-year and 4-year mortality. With respect to subtypes of EM, psychological mistreatment and caregiver neglect were associated with greater mortality risk, whereas the relationships between psychological mistreatment, caregiver neglect and mortality risk varied according to definitional criteria. Different definitions and subtypes of EM had different associations with mortality in Chinese-American older adults. This study challenges assumptions about consequences of EM and calls for customized interventions for EM in minority populations. J Am Geriatr Soc 67:S506-S512, 2019.


Controlled trial of penfluridol in acute psychosis.
A controlled study was made of penfluridol medication consisting of a single weekly oral dose of 30 mg in 30 patients with acute psychoses of varying type and origin. This medication was found to be effective. No significant side effects occurred.Several long-acting neuroleptics for injection are now available. The development of an oral compound of this type is an asset because of the manageability of the oral drug in the hands of family doctors and social psychiatrists.


Anxiety and Depression as Longitudinal Predictors of Mild Cognitive Impairment in Older Adults.
Few studies have dealt with the potential correlation between anxiety, depression, and cognitive impairment in community-dwelling older adults. This longitudinal study was conducted in the city of Montreal, Canada, with 352 older adults aged 55 years or more. The participants were interviewed at baseline and again 2 years later. The Montreal Cognitive Assessment (MoCA) score was estimated and compared between the 2 time points, the Composite International Diagnostic Interview (CIDI) was used to assess major depression and anxiety, and the K10 measured high psychological distress. Likewise, major depression, anxiety disorders, and psychological distress were evaluated at the 2 study time points. In older adults with a diagnosis of depression or anxiety at baseline, no significant reduction in the MoCA score indicating deterioration in cognitive function was found 2 years later. Nevertheless, in individuals with a high level of psychological distress at baseline, there was a significant reduction in MoCA scores 2 years later, indicating deterioration in cognition. The findings of the present study suggest that a high level of psychological distress in addition to environmental factors may constitute important predictors for cognitive health.


Cardiac arrest with successful cardiopulmonary resuscitation and survival induce histologic changes that correlate with survival time and lead to misdiagnosis in sudden arrhythmic death syndrome.
Sudden arrhythmic death syndrome (SADS), defined as sudden cardiac death (SCD) with a morphologically normal heart, is an important cause of sudden death. Hypoperfusion due to cardiac arrest followed by successful cardiopulmonary resuscitation (CPR) may induce histologic changes that mimic pathologic conditions. Detailed characterisation of such features and whether they could confound SADS diagnosis are not described. Retrospective observational study analysing all consecutive cases of sudden death prospectively referred to a UK national cardiac pathology centre between 2017 and 2021. Cases showing hypoperfusion features were identified after review of clinical information and examination by expert cardiac pathologists. Out of 2,568 SCD cases, 126 (4.9%) were identified with hypoperfusion changes. Macroscopically, the commonest finding was left ventricular focal or diffuse subendocardial haemorrhage (13.5%). Microscopically, haemorrhage and contraction band necrosis (n = 50, 37.7%), subendocardial acute infarction (n = 44, 34.1%), interstitial mixed inflammatory cell infiltrates (n = 31, 24.9%), healing granulation tissue (n = 9, 7.1%) and subendocardial fibrosis (n = 1, 0.7%) were observed. These changes correlated to duration of survival following resuscitation. In a subcohort of 41 cases, autopsy pathologists misinterpreted such changes as ischaemic myocardial infarction (n = 7; 17%), myocarditis (n = 5; 12.1%), or other pathologies (n = 2; 4.8%) in 14 SADS cases. We provide a comprehensive characterisation of hypoperfusion-related changes in the heart following successful CPR with survival, which are time related. These features can lead to diagnostic confusion among pathologists but knowledge of history of resuscitation with survival should help with general and expert pathology assessment and improve SADS diagnostic yield, prompting genetic screening of decedents' relatives.


Biochemistry of the autolytic processes in Antarctic krill post mortem. Autoproteolysis.
1. Autoproteolysis post mortem was examined at 0 degree C by following the changes in the major classes of krill (Euphausia superba and Euphausia crystallorophias) proteins and by liberation of peptides and free amino acids, and was based on experiments conducted on board expedition vessels in the Antarctic. 2. Primarily salt-soluble proteins were broken down during the first week of incubation, whereas water-soluble and insoluble proteins were degraded to a much smaller extent. The enzymes responsible for the hydrolysis presumably originate primarily from the digestive apparatus of the krill. 3. In general, the individual amino acids were released at rates corresponding to their relative occurrence in the bulk protein of the krill. Alanine was liberated in larger amounts than would be expected from the composition of the krill protein, and was evidently formed also by reactions other than proteolysis. Glutamic acid, and certain amino acids which presumably occur with high frequency adjacent to glumatic acid residues in the krill protein, were liberated only to a limited extent, and accumulated in smaller peptides. 4. During proteolysis, arginine seemed to be converted to some degree into ornithine, and on prolonged incubation conversion of arginine and lysine into their corresponding decarboxylation products, agmatine and cadaverine, appeared to take place.


Class XI Myosins Contribute to Auxin Response and Senescence-Induced Cell Death in Arabidopsis.
The integrity and dynamics of actin cytoskeleton is necessary not only for plant cell architecture but also for membrane trafficking-mediated processes such as polar auxin transport, senescence, and cell death. In Arabidopsis, the inactivation of actin-based molecular motors, class XI myosins, affects the membrane trafficking and integrity of actin cytoskeleton, and thus causes defective plant growth and morphology, altered lifespan and reduced fertility. To evaluate the potential contribution of class XI myosins to the auxin response, senescence and cell death, we followed the flower and leaf development in the triple gene knockout mutant xi1 xi2 xik (3KO) and in rescued line stably expressing myosin XI-K:YFP (3KOR). Assessing the development of primary inflorescence shoots we found that the 3KO plants produced more axillary branches. Exploiting the auxin-dependent reporters DR5::GUS and IAA2::GUS, a significant reduction in auxin responsiveness was found throughout the development of the 3KO plants. Examination of the flower development of the plants stably expressing the auxin transporter PIN1::PIN1-GFP revealed partial loss of PIN1 polarization in developing 3KO pistils. Surprisingly, the stable expression of PIN1::PIN1-GFP significantly enhanced the semi-sterile phenotype of the 3KO plants. Further we investigated the localization of myosin XI-K:YFP in the 3KOR floral organs and revealed its expression pattern in floral primordia, developing pistils, and anther filaments. Interestingly, the XI-K:YFP and PIN1::PIN1-GFP shared partially overlapping but distinct expression patterns throughout floral development. Assessing the foliar development of the 3KO plants revealed increased rosette leaf production with signs of premature yellowing. Symptoms of the premature senescence correlated with massive loss of chlorophyll, increased cell death, early plasmolysis of epidermal cells, and strong up-regulation of the stress-inducible senescence-associated gene SAG13 in 3KO plants. Simultaneously, the reduced auxin responsiveness and premature leaf senescence were accompanied by significant anthocyanin accumulation in 3KO tissues. Collectively, our results provide genetic evidences that Arabidopsis class XI myosins arrange the flower morphogenesis and leaf longevity via contributing to auxin responses, leaf senescence, and cell death.


Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.
Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ9-THC-induced atherosclerosis.


Intracranial aneurysms in patients with coarctation of the aorta: a prospective magnetic resonance angiographic study of 100 patients.
To determine the frequency of intracranial aneurysms (IAs) detected in patients with coarctation of the aorta (CoA) with use of magnetic resonance angiography. From January 1, 1980, to September 30, 2002, 277 adult patients with CoA were seen at the Mayo Clinic in Rochester, Minn, and were invited to participate in a study to detect IAs. Of these 277 patients (mean +/- SD age, 41.6 +/- 16.5; 70 men), 100 underwent cranial magnetic resonance angiography. Ten patients had an IA (95% confidence interval, 5%-18%), with a mean diameter of 3.5 mm (range, 2.0-8.0 mm). The frequency of IA was significantly higher than that predicted in the general population (10% vs 2%; P < .001). One patient had surgical intervention. No clinical or geographical differences were found between patients with CoA and IA and patients with CoA and no IA. The frequency of IA among patients with CoA is approximately 5-fold that of the general population. Although no risk factors were identified in this cohort, additional prospective evaluation is warranted. These data suggest that noninvasive cerebral imaging to screen for IA should be considered in patients with CoA.


Patient-Reported Outcomes During Immunotherapy for Metastatic Melanoma: Mixed Methods Study of Patients' and Clinicians' Experiences.
The benefits of electronic patient reported outcomes (PRO) questionnaires have been demonstrated in many settings, including in hospitals and patient homes. However, it remains to be investigated how melanoma patients and their treating clinicians experience the electronic self-reporting of side effects and the derived communication. The primary objective of this study was to examine patients' and clinicians' experiences with an eHealth intervention for weekly monitoring of side effects during treatment with immunotherapy. An eHealth intervention based on questions from the PRO-Common Terminology Criteria for Adverse Events (CTCAE) library was used and tested in a randomized clinical trial with patients receiving immunotherapy for malignant melanoma and clinicians at a university hospital in Denmark. On a weekly basis, patients reported their symptoms from home during the treatment via a provided tablet. The electronic patient reports were available to clinicians in the outpatient clinic. A mixed methods approach was applied to investigate the patients' and clinicians' experiences with the intervention. Data from patient experiences were collected in a short survey, the Patient Feedback Form. Moreover, a subset of the patients participating in the survey was interviewed about their experience. Furthermore, one focus group interview with clinicians was carried out to elucidate their views. A total of 57 patients completed the Patient Feedback Form, and 14 patients were interviewed. The focus group interview included 5 clinicians. Overall, patients and clinicians were satisfied with the tool. They believed it enhanced patients' awareness of side effects and increased their feeling of involvement. The patients reported that it was easy to fill out the questionnaire and that it made sense to do so. However, a minority of the patients expressed in the interviews that they did not believe that the health care professionals had seen their reports when they came to the clinic, and that the reporting did not lead to increased contact with the department. Overall, satisfaction with the eHealth intervention was high among patients and their treating clinicians. The tool was easy to use and contributed to greater symptom awareness and patient involvement. Thus, in terms of patient and clinician satisfaction with the tool, it makes sense to continue using the tool beyond the project period. ClinicalTrials.gov NCT03073031; https://tinyurl.com/tjx3gtu.


Trend of surgery for orbital cellulitis: An analysis of state inpatient databases.
To evaluate the trend and factors associated with surgical management of orbital cellulitis. Retrospective database study. Study using the State Inpatient Databases (SIDs) from 2008 to 2015. Patients with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for orbital cellulitis were identified in the SIDs for the following states: Arkansas, Florida, Iowa, Maryland, Nebraska, New York, and Wisconsin. Surgery was defined as an ICD-9-CM procedure code for orbitotomy and/or functional endoscopic sinus surgery. The trend of surgery over time was evaluated using the Cochran-Armitage test. Multivariable logistic regression models were used to identify patient- and hospital-level factors associated with surgery. From 2008 to 2013, the number of hospitalizations for orbital cellulitis ranged from 1,349 to 1,574, but declined to 865 in 2014. From 2008 to 2015, the number of surgeries ranged from 103 to 154. For children (n = 3,041), age, ophthalmologic comorbidity, and conjunctival edema were significantly associated with surgery, whereas for adults (n = 7,961), male gender, private insurance, optic neuritis, and cranial nerves III/VI/VI palsy were associated with surgery. Although the number of inpatient hospitalizations for orbital cellulitis has markedly declined, the number of surgeries for orbital cellulitis has remained fairly stable, leading to an observed higher proportion of hospitalized patients undergoing surgery. Future directions include extending the time frame to the present day to assess current rates of hospitalization and surgery. Knowledge of surgical trends and patient- and hospital-level characteristics associated with surgery may help improve management guidelines for and understanding of this vision-threatening disease. NA Laryngoscope, 130:567-574, 2020.


Plasticity in adult and ageing sympathetic neurons.
The nature of neural plasticity and the factors that influence it vary throughout life. Adult neurons undergo extensive and continual adaptation in response to demands that are quite different from those of early development. We review the main influences on the survival, growth and neurotransmitter expression in adult and ageing sympathetic neurons, comparing these influences to those at work in early development. This "developmental" approach is proposed because, despite the contrasting needs of different phases of development, each phase has a profound influence on the mechanisms of plasticity available to its successors. Interactions between neurons and their targets, whether effector cells or other neurons, are vital to all of these aspects of neural plasticity. Sympathetic neurons require access to target-derived diffusible neurotrophic factors such as NGF, NT3 and GDNF, as well as to bound elements of the extracellular matrix such as laminin. These factors probably influence plasticity throughout life. In adult life, and even in old age, sympathetic neurons are relatively resistant to cell death. However, they continue to require target-derived diffusible and bound factors for their maintenance, growth and neurotransmitter expression. Failure to maintain appropriate neuronal function in old age, for example in the breakdown of homeostasis, may result partly from a disturbance of the dynamic, trophic relationship between neurons and their targets. However, there is no clear evidence that this is due to a failure of targets to synthesize neurotrophic factors. On the neural side of the equation, altered responsiveness of sympathetic neurons to neurotrophic factors suggests that expression of the trk and p75 neurotrophin receptors contributes to neuronal survival, maintenance and growth in adulthood and old age. Altered receptor expression may therefore underlie the selective vulnerability of some sympathetic neurons in old age. The role of neural connectivity and activity in the regulation of synthesis of target-derived factors, as well as in neurotransmitter dynamics, is reviewed.


Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea.
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern globally; however, no comprehensive AMR data for gonococcal isolates cultured after 2006 in Korea have been published internationally. We determined the susceptibility of N. gonorrhoeae isolates cultured in 2011-13, the mechanism of extended-spectrum cephalosporin (ESC) resistance and the molecular epidemiology of gonococcal strains in Korea. In 2011-13, 210 gonococcal isolates were collected in Korea and their AMR profiles were examined by the agar dilution method. The penA, mtrR, penB, ponA and pilQ genes were sequenced in 25 isolates that were resistant to ESCs and 70 randomly selected isolates stratified by year. For molecular epidemiology, N. gonorrhoeae multiantigen sequence typing and MLST were performed. None of the N. gonorrhoeae isolates was susceptible to penicillin G and most were resistant to tetracycline (50%) and ciprofloxacin (97%). The rates of resistance to ceftriaxone, azithromycin, cefpodoxime and cefixime were 3%, 5%, 8% and 9%, respectively. However, all isolates were susceptible to spectinomycin. Twenty-one (84%) of the 25 ESC-resistant isolates contained the non-mosaic PBP2 XIII allele; however, the remaining 4 (16%) possessed the mosaic PBP2 X allele, which has been previously associated with ESC resistance including treatment failures. In Korea, susceptibility to spectinomycin remains high. However, the recent emergence of ESC-resistant N. gonorrhoeae strains, including strains possessing the PBP2 mosaic X and non-mosaic XIII alleles, is a major concern and enhanced AMR surveillance is necessary to prevent transmission of these strains.


Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell'Italia Meridionale Multicenter phase II study.
FOLFOX-4 and FOLFIRI are considered equivalent in terms of activity and efficacy as first-line chemotherapy in metastatic colorectal cancer (mCRC). The monoclonal antibody (mAb) cetuximab showed intrinsic activity as a single agent in mCRC and was approved in combination with CPT-11 for patients who failed previous CPT-11-based treatment. The purpose of this phase II study was to evaluate the activity and safety of FOLFOX-4 plus cetuximab in untreated mCRC patients. Untreated patients with measurable metastatic disease and expressing epidermal growth factor receptor (EGFR) received cetuximab at a loading dose of 400 mg/m(2), followed by weekly doses of 250 mg/m(2), in combination with the FOLFOX-4 regimen every 2 weeks for a maximum of 12 cycles, after which a maintenance program using cetuximab alone was allowed for a maximum of 6 months. Eighty-two unselected patients were screened; 70 were EGFR+ and entered the trial. Of the 67 assessable patients, the objective response rate was 64.2% (95% CI: 52.5-75.5%) and the tumor growth control rate was 94% (95% CI: 88-99%). All the objective responses except 1 were confirmed. In the group of patients with initially unresectable liver disease alone, 7/33 (21%) were resected. The median time to progression (TTP) and overall survival (OS) were 10.0 and 22.0 months, respectively. The treatment was well tolerated, with no treatment-related deaths, while 24.2% of the patients were affected by cutaneous toxicity of grade >2. Mutational analysis of the KRAS and BRAF genes was retrospectively performed on 35 of the 69 patients treated with cetuximab (51%). KRAS was mutated in 13 out of the 35 cases (37%), whereas no mutations were detected in the BRAF gene. A trend toward an association between KRAS mutations and objective response to treatment (p = 0.07) was demonstrated. Analysis of survival showed that patients harboring KRAS mutations had a trend toward worst TTP (p = 0.14) confirmed by age- and sex-adjusted Cox multivariate regression (hazard ratio, HR = 0.62; 95% CI: 0.36-1.06; p = 0.08). Indeed, KRAS mutations were significantly associated with worst OS in both unadjusted analysis (p = 0.047; log rank test) and age- and sex-adjusted Cox multivariate regression (HR = 0.458; 95% CI: 0.248-0.847; p = 0.01). These results suggest that the combination of FOLFOX-4 plus cetuximab is very active and obtains long TTP with an acceptable toxicity profile. Indeed, our results are in line with recent findings from phase II and phase III randomized studies providing strong evidence that the efficacy of anti-EGFR mAb is confined to patients with wild-type KRAS mCRC. Investigation of other predictive biomarkers may be useful to further define the responder population.


Fc-mediated functions and the treatment of severe respiratory viral infections with passive immunotherapy - a balancing act.
Passive immunotherapies have been used to treat severe respiratory infections for over a century, with convalescent blood products from recovered individuals given to patients with influenza-related pneumonia as long ago as the Spanish flu pandemic. However, passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (hIVIG) has not provided unequivocal evidence of a clinical benefit for severe respiratory infections including influenza and COVID-19. Efficacy trials, primarily conducted in late-stage disease, have demonstrated inconsistent efficacy and clinical benefit for hIVIG treatment of severe respiratory infections. To date, most serological analyses of convalescent plasma and hIVIG trial samples have focused on the measurement of neutralizing antibody titres. There is, however, increasing evidence that baseline antibody levels and extra-neutralizing antibody functions influence the outcome of passive immunotherapy in humans. In this perspective, findings from convalescent plasma and hIVIG trials for severe influenza, COVID-19 and respiratory syncytial virus (RSV) will be described. Clinical trial results will be discussed in the context of the potential beneficial and deleterious roles of antibodies with Fc-mediated effector functions, with a focus on natural killer cells and antibody-dependent cellular cytotoxicity. Overall, we postulate that treating respiratory viral infections with hIVIG represents a delicate balance between protection and immunopathology.


The homophilic adhesion molecule sidekick-1 contributes to augmented podocyte aggregation in HIV-associated nephropathy.
The collapsing glomerulopathy of HIV-associated nephropathy (HIVAN) is characterized by podocyte dedifferentiation and proliferation. In affected glomeruli, proliferating podocytes adhere in aggregates to form glomerular pseudocrescents and fill an enlarged Bowman's space. Previously, we reported that sidekick-1 (sdk-1), an adhesion molecule of the immunoglobulin superfamily, was highly up-regulated in HIV-1 transgenic podocytes. In the current work, we explore how sdk-1 overexpression contributes to HIVAN pathogenesis. Murine podocytes infected with HIV-1 virus expressed significantly more sdk-1 than control-infected cells. Podocytes stably transfected with an sdk-1 expression construct grew in large aggregates with a simplified morphology characterized by a disorganized actin cytoskeleton, changes similar to podocytes in HIVAN. In contrast to controls, HIV-1 infected podocytes adhered to stably transfected sdk-1 podocyte aggregates in mixing studies. Furthermore, substrate-released cell sheets of wild-type podocytes were readily dissociated by mechanical stress, whereas HIV-1 podocytes remained in aggregates. The number of HIV-1 podocyte aggregates was significantly reduced in cells expressing a short hairpin RNA (shRNA) construct specific for sdk-1 compared with cells expressing control shRNA. Finally, in a HIVAN mouse model, sdk-1 protein was detected in podocytes in collapsed glomerular tufts and in glomerular pseudocrescents. These findings suggest that sdk-1 is an important mediator of cellular adhesion in HIV-infected podocytes and may contribute to podocyte clustering that is characteristic of pseudocrescent formation in HIVAN.


Gender differences in the prevalence of hypertension in a representative sample of Iranian population: the Isfahan Healthy Heart Program.
Management and control of hypertension is an important potential health challenge that may result in considerable cardiovascular adverse events especially for women. In this population-based survey, we sought to determine the epidemiology of hypertension among women compared with men in a community sample of Iranians in the 2008s. Data were originated from the Isfahan healthy heart program (IHHP) that was designed and launched in 2000 in order to assess the efficacy of lifestyle interventions such as determining the cumulative prevalence of hypertension in a representative sample of Iranian women and to compare it to men. Blood pressure was measured in 12514 individuals (6123 men and 6391 women aged > or = 19 years) selected through multistage random cluster sampling in each sex and age groups. Baseline data were also collected using a special questionnaire and interviews by expert and trained nurses for this survey. It was revealed a significant increasing trend in the prevalence of hypertension in both urban and rural population in the two genders (p for trend <0.001). The prevalence of hypertension in women was estimated from 4.4 % in subjects aged < 30 years to 39.1% in the elderly aged > or = 60 years in urban population. Moreover, hypertension was also estimated from 8.6% in individuals aged < 30 years to 32.0% in the elderly aged > or = 60 years in rural population. Both systolic and diastolic blood pressures were frequently higher in women than in men aged 50-60 years. Women more than men are aware of their blood pressure changes and hypertension is more controlled and under pharmacological treatment in women. Our study supports the pivotal role of women-specific control and management of hypertension and emphasizes the global education programs about the importance of hypertension control and monitoring and also lifestyle modification for reducing the risk of hypertension in Iranian women. (www.actabiomedica.it).


Reconstruction of the right ventricle with diaphragm driven right ventricular wall device.
For the treatment of congenital cardiac anomalies associated with hypoplastic right ventricle such as tricuspid atresia, various methods have been used in clinical and experimental studies. Though these methods were effective, there remained still some problems such as postoperative right heart failure or restriction of indications for the cases associated with high pulmonary vascular resistance. In order to solve these problems, diaphragm driven right ventricular wall device (RVWD) was newly developed. The device is composed of hard outer housing and soft diaphragm made of polyurethane and actuated pneumatically triggered to R wave of ECG or left ventricular pressure. Characteristics of RVWD were checked using a mock circulation to find optimal driving condition for animal experiments. Acute experiments were carried out using 15 mongrel dogs. Right ventricular free wall was excised as wide as possible under hypothermic inflow occlusion and RVWD was sutured to the edges of right ventriculotomy. Hemodynamics were investigated with and without driving of RVWD for 6 to 24 hr. RVWD was able to maintain hemodynamics efficiently during immediate postoperative period. After body temperature and cardiac function returned to normal, systemic circulation could be maintained without driving of RVWD. From the results of this study, possibly of surgical correction of hypoplastic right ventricle using RVWD was presumed.


Lymphangiogenesis and its relationship with lymphatic metastasis and prognosis in malignant melanoma.
Regional lymph node metastasis is one of the important indicators of cutaneous malignant melanoma. Newly formed lymphatic vessels are considered to provide a route whereby tumor cells can migrate to the lymph nodes. Both vascular endothelial growth factors (VEGF) -C and -D have been confirmed to participate in tumor lymphangiogenesis, but the prognostic significance of VEGF-C, VEGF-D, and lymphangiogenesis in cutaneous malignant melanoma remains controversial. To clarify the effects of these factors and to evaluate the relationships between lymphangiogenesis, lymph node metastasis, and prognosis in patients with malignant melanoma, the expressions of VEGF-C, VEGF-D, and their receptor (VEGFR) -3 were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction. The expressions of both VEGF-C and VEGF-D proteins were concomitantly detected in the cytoplasm of the malignant cells. VEGF-C and VEGF-D expressions were associated with VEGFR-3 expression and were significantly correlated with both peritumoral lymphangiogenesis and lymph node metastasis. The incidence of peritumoral lymphatic vessels was significantly higher in lymph node metastatic melanomas than that in nonmetastatic melanomas. Univariate and multivariate analyses indicated that VEGF-C and VEGF-D were independent prognostic factors for overall survival and disease-free survival in patients with malignant melanoma. This study suggests that both VEGF-C and VEGF-D are involved in peritumoral lymphangiogenesis and lymphatic metastasis. VEGF-C and VEGF-D expression may be clinically useful indicators for prognostic evaluation in patients with cutaneous malignant melanoma.


The sulfone linker in solid-phase synthesis: preparation of 3,5-disubstituted cyclopent-2-enones.
The preparation of functionalized 3,5-disubstituted cyclopent-2-enones via a solid-phase sulfone linker strategy is described. Polystyrene/divinylbenzene sulfinate 1 underwent S-alkylation followed by alpha,alpha-dialkylation with cis-1,4-dichloro-2-butene to form polymer-bound 3-phenylsulfonylcyclopentenes 8. Subsequent epoxidation of the cyclopentene moiety in 8 was accomplished by treatment of mCPBA, and the resulting oxirane ring in resin 9 was opened with various nucleophiles, i.e., Grignard and cuprate reagents, azide ion, and amines. To complete the sulfone-based linker strategy, Swern or TPAP oxidation of 10 gave a transient gamma-ketosulfone, which underwent sulfinate elimination, thus cleaving the sulfone linker. Eleven 3,5-disubstituted cyclopent-2-enones (11) were prepared with this five-step process in 18-40% overall yield from solid-phase benzene sulfinate 1.


Prevalence and prediction of overweight and obesity among elementary school students.
The high rates of childhood overweight and obesity in the United States have generated interest in schools as sites for monitoring body mass index (BMI) information. This study established baseline values for a 5-year longitudinal assessment of BMI of elementary school children and examined variation across the schools, because little is known about factors that affect the distribution of overweight and obesity within school districts. Height and weight measurements were collected on 2317 elementary school children in 1 school district. BMI was calculated using the Centers for Disease Control and Prevention's NutStat program. Child characteristics included gender, age, eligibility for free and reduced lunch (proxy for socioeconomic status [SES]), school, grade, and ethnicity/race. Children were grouped into 2 BMI categories, <85th percentile or ≥85th percentile (overweight/obesity). Logistic regression was used to examine potential predictors of overweight/obesity. Prevalence of ≥85th percentile was 30.9%, 34.4%, 35.3%, 36.4%, 37.1%, and 44.5% for K-5, respectively. Prevalence of ≥85th percentile was highest among Hispanic children. Ethnicity was the strongest predictor of inclusion in the ≥85th percentile category followed by grade and free and reduced lunch eligibility. The data are consistent with the prevalence of overweight/obesity among American children and Hispanic children in particular. District prevalence of overweight/obesity is higher than available state statistics. Most of the BMI variation is accounted for by ethnicity, SES, and grade. The grade effect and high prevalence of overweight/obesity provide a rationale for BMI screening retention at the schools.


Errors in radiation oncology: a study in pathways and dosimetric impact.
As complexity for treating patients increases, so does the risk of error. Some publications have suggested that record and verify (R&V) systems may contribute in propagating errors. Direct data transfer has the potential to eliminate most, but not all, errors. And although the dosimetric consequences may be obvious in some cases, a detailed study does not exist. In this effort, we examined potential errors in terms of scenarios, pathways of occurrence, and dosimetry. Our goal was to prioritize error prevention according to likelihood of event and dosimetric impact. For conventional photon treatments, we investigated errors of incorrect source-to-surface distance (SSD), energy, omitted wedge (physical, dynamic, or universal) or compensating filter, incorrect wedge or compensating filter orientation, improper rotational rate for arc therapy, and geometrical misses due to incorrect gantry, collimator or table angle, reversed field settings, and setup errors. For electron beam therapy, errors investigated included incorrect energy, incorrect SSD, along with geometric misses. For special procedures we examined errors for total body irradiation (TBI, incorrect field size, dose rate, treatment distance) and LINAC radiosurgery (incorrect collimation setting, incorrect rotational parameters). Likelihood of error was determined and subsequently rated according to our history of detecting such errors. Dosimetric evaluation was conducted by using dosimetric data, treatment plans, or measurements. We found geometric misses to have the highest error probability. They most often occurred due to improper setup via coordinate shift errors or incorrect field shaping. The dosimetric impact is unique for each case and depends on the proportion of fields in error and volume mistreated. These errors were short-lived due to rapid detection via port films. The most significant dosimetric error was related to a reversed wedge direction. This may occur due to incorrect collimator angle or wedge orientation. For parallel-opposed 60 degrees wedge fields, this error could be as high as 80% to a point off-axis. Other examples of dosimetric impact included the following: SSD, approximately 2%/cm for photons or electrons; photon energy (6 MV vs. 18 MV), on average 16% depending on depth, electron energy, approximately 0.5 cm of depth coverage per MeV (mega-electron volt). Of these examples, incorrect distances were most likely but rapidly detected by in vivo dosimetry. Errors were categorized by occurrence rate, methods and timing of detection, longevity, and dosimetric impact. Solutions were devised according to these criteria. To date, no one has studied the dosimetric impact of global errors in radiation oncology. Although there is heightened awareness that with increased use of ancillary devices and automation, there must be a parallel increase in quality check systems and processes, errors do and will continue to occur. This study has helped us identify and prioritize potential errors in our clinic according to frequency and dosimetric impact. For example, to reduce the use of an incorrect wedge direction, our clinic employs off-axis in vivo dosimetry. To avoid a treatment distance setup error, we use both vertical table settings and optical distance indicator (ODI) values to properly set up fields. As R&V systems become more automated, more accurate and efficient data transfer will occur. This will require further analysis. Finally, we have begun examining potential intensity-modulated radiation therapy (IMRT) errors according to the same criteria.


Effects of verapamil and diltiazem on acute stroke in cats.
To test the effect of verapamil and diltiazem in acute stroke, three groups of mongrel cats of either sex underwent occlusion of the middle cerebral artery (MCA) via a transorbital approach under ketamine anesthesia. The first group served as controls, the second received an intravenous infusion of verapamil (0.1 microgram/kg/min), and the third received an intravenous infusion of diltiazem (0.1 to 1.0 microgram/kg/min). All drug infusions began 2 hours before MCA occlusion and continued for the remainder of the experiment. Before and for up to 24 hours after MCA occlusion, regional cerebral blood flow (rCBF), somatosensory evoked potentials (SSEP's), arterial blood gases, blood pressure, temperature, and hematocrit were measured at least every 2 hours. At the experiment's end, brains were perfused with India ink, removed, sliced, photographed for determination of nonperfused brain area, and weighed, dried, and reweighed for H2O content determination. In these studies, verapamil was associated with worsening of rCBF in ischemic regions and inappropriate increases in rCBF in nonischemic regions, indicating intracerebral steal. Diltiazem increased rCBF in marginally ischemic regions. Changes in SSEP's paralleled blood flow changes, with verapamil decreasing amplitude and conduction velocity while diltiazem slightly improved conduction in the ischemic brain. Verapamil increased the area of nonperfused brain and the content of cerebral H2O. Diltiazem-treated animals had decreased cerebral H2O content, but had a marked increase in the area of nonperfused brain, a finding associated with the high incidence of transtentorial herniation in the diltiazem-treated animals. These findings agree with in vitro studies demonstrating high sensitivity of cerebral blood vessels to calcium channel blockers. These studies further support the notion that calcium channel blockers probably affect several different classes of calcium channels, at different brain sites.


Relative roles of K region and bay region towards determining the carcinogenic potencies of polycyclic aromatic hydrocarbons.
Using the quantum mechanical MINDO/3 method a bond reactivity index based on superdelocalization of electrons in a compound has been formulated in order to estimate the relative carcinogenic properties of polycyclic aromatic hydrocarbons. The values of the index calculated for the K region as well as the bay region suggest that a knowledge of the reactivities of both regions is necessary for a reasonable estimation of the relative carcinogenic potencies of PAHs. However, no direct relationship between the two reactivity indices was observed in the calculations. It was found that the results for the bay-region reactivity index correlated well with the relative carcinogenic potencies of the molecules.


Is thyroid stunning clinically relevant? A retrospective analysis of 208 patients.
Current guidelines have advised against the performance of (131)I-iodide diagnostic whole body scintigraphy (dxWBS) to minimize the occurrence of stunning, and to guarantee the efficiency of radioiodine therapy (RIT). The aim of the study was to evaluate the impact of stunning on the efficacy of RIT and disease outcome. This retrospective analysis included 208 patients with differentiated thyroid cancer managed according to a same protocol and followed up for 12-159 months (mean 30 ± 69 months). Patients received RIT in doses ranging from 3,700 to 11,100 MBq (100 mCi to 300 mCi). Post-RIT-whole body scintigraphy images were performed 10 days after RIT in all patients. In addition, images were also performed 24-48 hours after therapy in 22 patients. Outcome was classified as no evidence of disease (NED), stable disease (SD) and progressive disease (PD). Thyroid stunning occurred in 40 patients (19.2%), including 26 patients with NED and 14 patients with SD. A multivariate analysis showed no association between disease outcome and the occurrence of stunning (p = 0.3476). The efficacy of RIT and disease outcome do not seem to be related to thyroid stunning.


Pain control and cultural norms and expectations after closed femoral shaft fractures.
The purpose of this observation-cohort survey study was to compare the analgesia given and satisfaction with analgesia after a uniform orthopedic injury and operation in culturally disparate settings. Twenty-five patients with isolated closed femoral shaft fractures treated with intramedullary rod fixation within 1 week of injury were retrospectively evaluated at two urban hospitals in the United States. They were compared with a matched group from three urban hospitals in Vietnam (two in Hanoi and one in Ho Chi Minh City [Saigon]). Ages and sex did not differ significantly between the two groups. The mean weight of the Vietnamese group was significantly less than that of the US group (58 vs. 81 kg). During the 14 days following injury, the Vietnamese and American groups were given a mean of 0.9 mg/kg per day versus 30.2 mg/kg per day of morphine equivalent units, respectively. Two (8%) of the Vietnamese group felt their pain control had been inadequate, versus 20 (80%) of the US group. Similarly, 2 (8%) of the US group and 7 (28%) of the Vietnamese group felt they had received "too much" pain medication. Mean heart rates during the first 5 days after surgery were not significantly different in the two groups. Only 4% of the US group felt they had had an accurate impression of how much a femur fracture would hurt prior to the injury, whereas 76% of Vietnamese patients responded that they imagined such an injury would be approximately as painful as it was. Results were similar for preconceptions of pain as a result of surgery and during the postoperative period. More than 50% of patients from the US group felt there must be some explanation other than the femur fracture to explain the severity of their pain, such as infection, missed injury, hardware failure, or inappropriate medical care. Despite much higher administration of narcotic analgesia, American patients with femoral shaft fractures were much more dissatisfied with their analgesic results. In assessing the recommended dosing for "adequate analgesia" and "analgesic requirements," determinations may depend less upon tissue injury than upon cultural norms and patient expectations.


Effects of long-term, medically supervised, drug-free treatment and methadone maintenance treatment on drug users' emergency department use and hospitalization.
We examined the effect of drug treatment in 1996 on repeated (> or =2) emergency department visits and hospitalization in 1997 in a cohort of New York State Medicaid-enrolled human immunodeficiency virus (HIV)-positive and HIV-negative drug users. In HIV-positive drug users, the adjusted odds of repeated emergency department visits were increased for those receiving no long-term treatment (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.04-2.75), whereas the adjusted odds for those receiving methadone treatment and those receiving drug-free treatment for > or =6 months did not differ. The adjusted odds of hospitalization in the HIV-positive group were higher for those receiving long-term methadone treatment (OR, 1.69; 95% CI, 1.14-2.55) and for those receiving no long-term treatment (OR, 1.91; 95% CI, 1.29-2.88), compared with those receiving drug-free treatment. In the HIV-negative group, these associations were similar but weaker. For both HIV-positive and HIV-negative drug users, long-term drug-free treatment was at least as effective as long-term methadone treatment in reducing use of services indicative of poorer access to care and/or poorer health.


Effect of lysozyne on the recovery of heated Clostridium botulinum spores.
Lysozyme in the recovery medium increased the recovery of heated spores, thereby raising the measured heat resistance of type E Clostridium botulinum spores about 1,800-fold and type A spores up to 3-fold.


[In vitro drug interactions and their importance in anesthesiologic practice].
The potential for in vitro drug interactions is great in anaesthesiology because of routine intravenous comedication. When the drug is applied directly into (via) the injection port of the cannula most of these interactions are overlooked, whereas others show no visible signs. Chemical interactions depend on pH changes, formation of insoluble salts, oxidation and reduction, complex formation, or hydrolysis. Physical interactions are caused by changing of solvent system polarity, salting out, emulsion cracking or sorption. Solving the problem requires information (1) and precautions in respect of the mode of application (2). (1) Anaesthesiologists should know the most frequent mechanisms. Glucose infusions cannot be considered as safe carrier solutions for admixtures. Pharmacological databases should offer as much information as possible on incompatibility. (2) Injections into a separate line or lumen with a sodium chloride infusion are safe. Admixture is recommended only if compatibility is known.


Number of biopsies in diagnosing pulmonary nodules.
To determine the number of specimens to be obtained from pulmonary lesions to get the highest possible accuracy in histological work-up. A retrospective evaluation (January 1999 to April 2004) covered 260 patients with thoracic lesions who underwent computer tomography (CT)-guided core-cut biopsy in coaxial technique. All biopsies were performed utilizing a 19 gauge introducer needle and a 20 gauge core-cut biopsy needle. In all, 669 usable biopsies were taken (from 1-5 biopsies in each setting). The specimens were marked sequentially and each biopsy was worked up histologicaly. The biopsy results were correlated to histology after surgery, clinical follow-up or autopsy. The number of biopsies was determined that is necessary to achieve the highest possible accuracy in diagnosing pulmonary lesions. In 591 of 669 biopsies (88.3%), there were correct positive results. The overall accuracy was 87.4%. In 193 of 260 (74.2%) patients, a suspected malignancy was confirmed. In 50 of 260 (19.2%) patients, a benign lesion was correctly diagnosed. Seventeen (6.5%) patients were lost to follow-up. The first, second and third biopsies had cumulative accuracies of 63.6%, 89.2% and 91.5%, respectively (P < 0.02). More biopsies did not show any higher impact on accuracy. For the highest possible accuracy in diagnosing pulmonary lesions by CT-guided core-cut biopsy, at least three usable specimens are recommended to be taken.


Epstein-Barr Virus Induces Expression of the LPAM-1 Integrin in B Cells In Vitro and In Vivo.
Epstein-Barr virus (EBV) infects the oropharynx but, surprisingly, frequently induces B cell proliferation in the gut of immunosuppressed individuals. We found that EBV infection in vitro induces the expression of the LPAM-1 integrin on tonsillar B cells and increases it on peripheral blood cells. Similarly, LPAM-1 was induced in the tonsils of patients undergoing primary infectious mononucleosis. EBV-induced LPAM-1 bound to the MAdCAM-1 addressin, which allows B cell homing to the gastrointestinal mucosa-associated lymphoid tissue (GALT). Thus, we hypothesized that EBV-induced LPAM-1 could induce relocation of infected B cells from the tonsil to the GALT. In situ hybridization with an EBER-specific probe revealed the frequent presence of EBV-infected cells in the pericolic lymph nodes of healthy individuals. Relocation of infected B cells into the GALT would expand the EBV reservoir, possibly protecting it from T cells primed in the oropharynx, and explain why EBV induces lymphoid tumors in the gut.IMPORTANCE EBV causes tumors in multiple organs, particularly in the oro- and nasopharyngeal area but also in the digestive system. This virus enters the body in the oropharynx and establishes a chronic infection in this area. The observation that the virus causes tumors in the digestive system implies that the infected cells can move to this organ. We found that EBV infection induces the expression of integrin beta 7 (ITGB7), an integrin that associates with integrin alpha 4 to form the LPAM-1 dimer. LPAM-1 is key for homing of B cells to the gastrointestinal tract, suggesting that induction of this molecule is the mechanism through which EBV-infected cells enter this organ. In favor of this hypothesis, we could also detect EBV-infected cells in the lymph nodes adjacent to the colon and in the appendix.