Effects of dopamine D2 agonist quinpirole on neuronal activity of anterior cingulate cortex and striatum in rats.
The influence of acute D2 agonist quinpirole on locomotor activity has been effectively characterized. However, few studies have addressed the dynamic changes in neuronal activity of the anterior cingulate cortex (ACC) and striatum (STR), two crucial regions for cognitive and motor functions, after quinpirole administration. This study was conducted in order to acquire detailed information on the evoked activity of the neurons in the ACC and STR after acute quinpirole administration. Multichannel electrophysiological recording was used for tracking neuronal activity in the ACC and STR of urethane-anesthetized rats after administration of saline or 0.05 or 0.5 mg/kg quinpirole. In contrast to the responses to saline, quinpirole dose-dependently increased the ratio of neurons, the activity of which was inhibited in the ACC and STR. By examining the ensemble neuronal activities of inhibition-responded neurons, there was no significant activity difference among the "treatments" (saline and low- and high-dose quinpirole), the "periods" (the duration of 0-15 and 16-45 min after i.v. injection), and the interaction between "treatments" and "periods." Regarding activation-responded neurons, however, there was a significant "periods" difference in both ACC and STR, and the activity of 16-45 min was significantly higher than the activity of 0-15 min after high-dose quinpirole administration in ACC (p < 0.05) and STR (p < 0.001). Dose-dependent ACC and STR neuronal responses to quinpirole may offer a possible mechanism for understanding the locomotor responses to quinpirole in behaving rats. The late excitatory effect of high-dose quinpirole in the STR further suggests that this region would be critical for the activation of locomotor activity.


Familial and sporadic porphyria cutanea: two different diseases.
Uroporphyrinogen (URO) decarboxylase was measured in hemoglobin-free erythrocytes from subjects with familial porphyria cutanea: the mean activity was about 50% of that found in erythrocytes from normal subjects. Asymptomatic carriers were always found in the family. No enzyme deficiency was found in erythrocytes from subjects with sporadic porphyria cutanea. The measurement of URO decarboxylase in erythrocytes seems to allow an easy distinction between these two groups of porphyria cutanea.


Litomosoides pardinasi n. sp. (Nematoda, Onchocercidae) from two species of cricetid rodents in northern Patagonia, Argentina.
Seventy-seven cricetid rodents, corresponding to six different species, deposited at the Mammal Collection at Centro Nacional Patagónico, Puerto Madryn, Chubut, were examined for parasites. Litomosoides pardinasi n. sp. is described parasitizing the pleural and abdominal cavities of Phyllotis xanthopygus (Phyllotini) and the abdominal cavity of Oligoryzomys longicaudatus (Oryzomynii) in the northern Patagonia, Argentina. The new species is included in the carinii group, characterized by the presence of a right spicule with a dorsal heel and a terminal cap well cuticularized; left spicule composed with a handle longer or as long as the blade, and the blade constituted by a cuticularized distal filament. Litomosoides pardinasi n. sp. possesses a buccal capsule tubular with an anterior enlargement, and a smooth cavity; four labial and two dorsal cephalic papillae; vulva posterior to the esophagus-intestinal junction; male tail with three to five pairs of symmetric postcloacal papillae; female tail slender; vagina globular and small. This is the first record for a filarioid in a Phyllotini rodent and the southernmost record of any filarioid species worldwide.


The interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the lacrimal gland.
Pleomorphic adenoma (PA) is the most common tumour of the lacrimal gland, but very little is known about its biology. It has a tendency to recur and an ability to transform into the high-grade malignancy carcinoma ex pleomorphic adenoma (ca-ex-PA), which is also largely unexplored. In this study, we examine the expression of the interleukin-6/Janus kinase/STAT3 (IL-6/JAK/STAT3) pathway components in PA and ca-ex-PA. Sixteen PAs and two ca-ex-PAs were examined with immunohistochemistry. Seven PAs were subjected to microdissection and subsequent qPCR. The IL-6/JAK/STAT3 pathway was overexpressed in PA compared to normal lacrimal gland. Overexpression of phosphorylated JAK1 (p-JAK1) and cyclin D1 was significantly overexpressed in ductal cells compared with myoepithelial cells in PA. A shift from p-JAK1 to p-JAK2 and p-Tyk2 overexpression was seen between PA and ca-ex-PA, combined with a high p-STAT3 expression in the latter. The IL-6/JAK/STAT3 pathway is overexpressed in PA, and this overexpression was even more pronounced in ca-ex-PA, with a shift in the JAKs mediating STAT3 phosphorylation. Future studies are needed to clarify whether PA and ca-ex-PA could be treated with targeted therapy directed against components of the IL-6/JAK/STAT3 pathway.


Effects of warming and nitrogen deposition on CH4, CO2 and N2O emissions in alpine grassland ecosystems of the Qinghai-Tibetan Plateau.
Increases in nitrogen (N) deposition along with climate warming can change the dynamics of carbon and nitrogen in the soil, and alter greenhouse gases (GHGs) fluxes. To examine how N deposition and warming affect GHGs (CH4, CO2 and N2O) fluxes in alpine grasslands, we conducted experiments in an alpine meadow (AM), alpine-steppe (AS), and alpine cultivated grassland (CG) on the Qinghai-Tibetan Plateau (QTP). We simulated N deposition by treating soil with ammonium nitrate (NH4NO3) (8kgNha-1year-1), a warming treatment using an open top chamber (OTC) was carried out, and a combined treatment of warming and N deposition (8kgNha-1year-1) was conducted. The GHGs were collected during early, peak, and late plant growing seasons, i.e., May, August, and October of 2015, respectively, using a static chamber. We found, in general, neither N deposition nor warming solely altered CH4 and N2O fluxes in the alpine grasslands. The N deposition under warming conditions reduced CO2 emission significantly. The reduction of CO2 emission was most significant in the alpine steppe. The effects of climatic warming and N deposition on the GHGs varied greatly across the grassland types and the growing seasons. The cultivated grasslands were much more unstable than the native grasslands in CH4 uptake. In can be concluded the N deposition associated with human activities may buffer the CO2 emission in the alpine grassland ecosystems in terms of climate changes on the QTP.


A bradykinin antagonist inhibited nitric oxide generation and thromboxane biosynthesis in acute pancreatitis.
The effect of bradykinin on nitric oxide generation and eicosanoid production in the early stage of an experimental model of acute necrotizing pancreatitis induced by sodium taurocholate has been evaluated. We have compared the effect of administering a long-acting bradykinin antagonist, HOE 140, and an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl esther L-NAME) on pancreatic prostanoid synthesis. Plasma lipase levels were increased after acute pancreatitis induction, and reduced after HOE 140 or L-NAME administration. Nitric oxide production and thromboxane B2 levels were increased after pancreatitis induction and the increases were reduced by L-NAME or HOE 140 administration. In contrast, increased prostacyclin production, reflected as 6-keto-PGF1 alpha levels, was not modified by L-NAME or HOE 140. Bradykinin seems to be involved in nitric oxide and thromboxane synthesis during the initial phases of acute necrohemorrhagic pancreatitis.


Clinical Imaging of Tumor Metabolism with ¹H Magnetic Resonance Spectroscopy.
Magnetic resonance spectroscopy (MRS) is a noninvasive functional technique to evaluate the biochemical behavior of human tissues. This property has been widely used in assessment and therapy monitoring of brain tumors. MRS studies can be implemented outside the brain, with successful and promising results in the evaluation of prostate and breast cancer, although still with limited reproducibility. As a result of technical improvements, malignancies of the musculoskeletal system and abdominopelvic organs can benefit from the molecular information that MRS provides. The technical challenges and main applications in oncology of (1)H MRS in a clinical setting are the focus of this review.


Amino acid sequence of chicken fibrinopeptide A.
Chicken fibrinopeptide A was isolated and the complete amino acid sequence was established. It is a pentadecapeptide with the sequence of Gln(Pyr)-Asp-Gly-Lys-Thr-Thr-Phe-Glu-Lys-Glu-Gly-Gly-Gly-Gly-Arg and is homologous with mammalian fibrinopeptide A. Two peptides which appear to be derivatives of fibrinopeptide A were also isolated. One of these appeared to be fibrinopeptide A with NH2-terminal pyroglutamic acid; the other was fibrinopeptide A which lacked the COOH-terminal arginine residue.


Nuclear DNA damage signalling to mitochondria in ageing.
Mitochondrial dysfunction is a hallmark of ageing, and mitochondrial maintenance may lead to increased healthspan. Emerging evidence suggests a crucial role for signalling from the nucleus to mitochondria (NM signalling) in regulating mitochondrial function and ageing. An important initiator of NM signalling is nuclear DNA damage, which accumulates with age and may contribute to the development of age-associated diseases. DNA damage-dependent NM signalling constitutes a network that includes nuclear sirtuins and controls genomic stability and mitochondrial integrity. Pharmacological modulation of NM signalling is a promising novel approach for the prevention and treatment of age-associated diseases.


Occurrence and partitioning behavior of perfluoroalkyl acids in wastewater effluent discharging into the Long Island Sound.
Perfluoroalkyl acids (PFAAs) were measured in aqueous and suspended particulate matter (SPM) fractions in the final effluents from 12 wastewater treatment facilities located around the Connecticut shoreline. Aqueous phase concentrations ranged from 53 to 198 ng/L for ∑PFAAs with ≤7 perfluorinated carbons (CF2) and 2-73 ng/L for >7 CF2 PFAAs. Predominant PFAAs associated with effluent derived SPM were perfluorodecanoic acid and perflurorooctane sulfonic acid, detected in 48% and 52% of samples in concentrations ranging from <LOQ-1770 ng/g and <LOQ-2750 ng/g respectively. Based on the range of concentrations detected and the average flow of final effluent to the Long Island Sound (LIS), average total annual PFAA mass loads from wastewater treatment facilities to the LIS is estimated in the range of 70-315 kg/year, with 4-100 kg/year consisting of >7 CF2 PFAAs. Partitioning coefficients (log KOC) derived for effluent water and SPM phases (4.2 ± 0.3, 4.4 ± 0.4, 5.1 ± 0.2 and 5.3 ± 0.2 for PFOA, PFNA PFDA and PFUnA; 4.5 ± 0.2 and 5.2 ± 0.2 for PFOS and PFHsX respectively) were found to be of similar magnitude to aeration tank particles, though 0.5 to 2 log units greater than sludge solids and to natural system particulates including riverine SPM, estuarine SPM and sediments. Results from this study suggest that effluent derived suspended particulate matter could be an effective vector in the transport of long-chained PFAAs through wastewater treatment into receiving waters, and a potential vector to the local food chain.


Application effect of Kolb's experiential learning theory in clinical nursing teaching of traditional Chinese medicine.
This study aimed to explore the practical application and effect of Kolb's experiential learning theory in the clinical nursing training of traditional Chinese medicine (TCM). This study is a quasi-experimental study. Eighty clinical nurses from a class-III grade-A general hospital were enrolled in 2020 and 2021, respectively, as research subjects. The subjects in the control group were trained in "theory explanation, clinical practice, summary and Q&A, [and] centralized examination." The subjects in the experimental group were first grouped according to Kolb's experiential learning style. The training followed a "problem-exploration-practice-exploration-theory-explanation-summary-centralized examination" structure based on Kolb's experiential learning cycle, the training place is Conference Room 1 of the hospital. The training time is from February to August 2020 and 2021. The application effect of the experiential learning theory was evaluated by analyzing course evaluation questionnaires and the final examination results. The total score of the course evaluation questionnaire of the experimental group was 112.23 ± 5.88. The difference compared with the control group was statistically significant (P < .01). In the experimental group, the theoretical score was 85.27 ± 3.29, and the operational score was 85.36 ± 3.01. The differences compared with the control group were statistically significant (P < .01). The application of Kolb's experiential learning theory to the training of TCM clinical nursing can make the clinical practice of TCM nursing more "scientific" and the training more effective, and it can improve the subjective initiative of students.


New approach to the practical synthesis of tri- or tetrasubstituted pyrimidine derivatives: a four-component coupling reaction from a functionalized silane, two types of aromatic nitriles, and acetals.
[reaction: see text] A new approach to the synthesis of tri- or tetrasubstituted pyrimidines by a four-component coupling reaction using a functionalized silane, two types of aromatic nitriles, and an acetal is described. The efficient transformation of the pyrimidine framework consisting of an isoxazolyl ring and an ethoxy group to the 1,3,8-triazanaphthalene skeleton also proceeded in nearly quantitative yield.


Assessment of left ventricular function by isometric handgrip exercise after thrombolysis in patients with refractory unstable angina.
The handgrip test has been proposed for the evaluation of the hemodynamic reserve in patients with coronary artery disease and to quantitate the impairment of left ventricular (LV) function. The present study was designed to evaluate the effect of thrombolytic therapy in patients with refractory unstable angina in order to test the hypothesis that a reduction in intracoronary thrombosis could ameliorate their hemodynamic response to the handgrip test. During left heart catheterization, 20 patients with refractory unstable angina of recent onset performed a handgrip test before (HG1) and 24-72 hours after (HG2) being randomized to receive recombinant tissue-type plasminogen activator or placebo, according to a double-blind parallel group design. HG1 induced an increase in heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during baseline handgrip were highly different in individual patients, resulting in a trend toward an increase. Similarly, a different individual response was observed in the behavior of the isovolumetric and relaxation indices. In comparison with HG1, no difference was detected during HG2 in the 2 treatment groups with respect to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures, +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable angina of recent onset, the handgrip test performed before and after thrombolysis did not prove to be useful in assessing directional changes of LV performance, mainly because of the different individual response to the baseline handgrip test.


[Health information behaviour and health literacy on COVID-19 vaccination of the general population in Germany-findings from the CoSiD study].
Although COVID-19 vaccination reduces severe disease progression as well as hospitalisations and deaths, every fourth to fifth person in Germany is not vaccinated against COVID-19. Effective information and communication measures are needed to reach these people. For this, it is important to know the information behaviour as well as the health competences in the area of COVID-19 vaccination, especially of previously unvaccinated people. The third representative population survey (November/December 2021; n = 4366) of the CoSiD study (Corona vaccination in Germany) was conducted as a combined telephone and online survey. Bivariate correlations between reported information behaviour, subjective health literacy and vaccination status and intention are investigated. In addition, multivariate correlations of socio-demographic characteristics and subjective health literacy are analysed. Undecided people and people that are more likely to vaccinate were overall less likely to report a good subjective level of information (46.1%; 41.1%) and competences in evaluating information about COVID-19 vaccination (36.5%; 38.8%) as well as decision making (39.0%; 35.9%). Unvaccinated people without vaccination intentions are more likely to report observing information rated as untrustworthy or wrong (60.3%). People with a lower level of education, younger people and people with a migration background report lower levels of heath literacy. Communication measures to promote health literacy should specifically address people with uncertain vaccination intentions as well as younger people, people with lower levels of education and people with a migration background.


The effect of binge fetal alcohol exposure on the number of vasoactive intestinal peptide-producing neurons in fetal sheep brain.
Previously we demonstrated that fetal alcohol exposure attenuates hypoxic cerebral vasodilation in fetal and neonatal sheep. One mechanism may be altered expression of brain vasoactive substances. We hypothesized that early fetal alcohol exposure alters the number of fetal neurons expressing vasoactive intestinal peptide (VIP), a potent cerebral vasodilator. Thirteen pregnant ewes received daily i.v. infusions of alcohol (1.5 g/kg) or saline on days 30-54 of gestation (term = 145 days). Fourteen fetal brains (6 alcohol-exposed, 8 saline control) were obtained on gestational day 126. Using unbiased stereology, we counted immunohistochemically-labeled VIP neurons in one half of each forebrain with an optical fractionator. The total NeuN-labeled neurons were similarly counted. Alcohol-exposed fetal sheep brains had fewer VIP-immunopositive neurons per hemisphere, 14.6 x 10(6), compared to saline controls, 19.8 x 10(6). The total neuron number was not different, 1.19 x 10(9) versus 1.23 x 10(9) respectively, indicating a selective decrease in VIP neurons as a result of alcohol exposure. In sheep, alcohol exposure early in gestation is associated with fewer VIP-producing neurons later in gestation compared to saline controls; therefore, alcohol-related changes in the number of VIP-expressing neurons may be responsible in part for the attenuated hypoxic cerebral vasodilation described in fetal and neonatal sheep exposed to alcohol earlier in gestation.


Examining the consequences of tinnitus using the multidimensional perspective.
Tinnitus is one of the most frequent chronic conditions in adults with wide range of consequences. The aim of the current study was to determine the problems and life effects reported by individuals with tinnitus using the International Classification of Functioning, Disability and Health (ICF) framework. The study used a cross-sectional survey design. A total of 344 individuals with tinnitus completed a series of questionnaires. The responses to open-ended questions were linked to ICF categories. Activity limitations and participation restrictions were most dominant consequence of tinnitus followed by effect on the body function with limited emphasis on the contextual factors. Frequently reported responses to body function involved emotional functions (b152), attention function (b140), and sleep functions (b134). Commonly reported responses to activity limitations and participation restrictions were recreation and leisure (d920), conversation (d350), communicating with-receiving-spoken messages (d310), listening (d115), and remunerative employment (d850). Sound intensity (e2500) and sound quality (e2501) were the frequently reported responses to environmental factors. Coping styles, past and present experiences, and lifestyle were the most frequently occurring personal factors. The study highlighted some key influencing factors of tinnitus in different ICF domains which can be helpful in rehabilitation planning.


The association between glycemic index, glycemic load, and metabolic syndrome: a systematic review and dose-response meta-analysis of observational studies.
The association of glycemic index (GI) and glycemic load (GL) with metabolic syndrome (MetS) is controversial. Therefore, we conducted this first systematic review and dose-response meta-analysis of observational studies to quantify these associations. We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies up to 1 April 2019. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated by a random-effects model. This study was registered with PROSPERO (CRD42019131788). We included eight high-quality (n = 5) or medium-quality (n = 3) cross-sectional studies in the final meta-analysis, comprising 6058 MetS events and 28,998 participants. The summary ORs of MetS for the highest versus lowest categories were 1.23 (95% CI 1.10-1.38, I2 = 0, tau2 = 0, n = 5) for dietary GI, 1.06 (95% CI 0.89-1.25, I2 = 36.2%, tau2 = 0.0151, n = 6) for dietary GL. The summary OR was 1.12 (95% CI 1.00-1.26, I2 = 0, tau2 = 0, n = 3) per 5 GI units, 0.96 (95% CI 0.83-1.10, I2 = 33.4%, tau2 = 0.0059, n = 2) per 20 GL units. Dietary GI was positively associated with the prevalence of MetS. However, no significant association was found between dietary GL and the prevalence of MetS. Further studies with prospective design are needed to establish potential causal relationship between dietary GI and the MetS.


A Review of the Potential Local Mechanisms by Which Exercise Improves Functional Outcomes in Intermittent Claudication.
Intermittent claudication (IC) is a common condition which is associated with significant quality of life limitation. National Institute for Health and Care Excellence guidelines recommend a group-based supervised exercise program as the primary treatment option for claudication, based on clinical and cost effectiveness. This review aims to assess the mechanisms by which exercise improves outcomes in patients with IC. MEDLINE, EMBASE, and PubMed were searched using the search strategy "claudication" [AND] "exercise" [AND] "mechanisms." Searches were limited from 1947 to October 2014. Only full-text articles published in the English language in adults (over 18 years of age) were eligible for the review. Any trial involving a nonsupervised exercise program was excluded. Abstracts identified by the database search were interrogated for relevance and citations from the shortlisted papers were hand searched for relevant references. The search yielded a total of 112 studies, of which 42 were duplicates. Forty-seven of the remaining 70 were deemed appropriate for inclusion in the review. Exercise is the first-line treatment for IC. Supervised exercise programs improve walking distances, endothelial and mitochondrial function, muscle strength, and endurance. Furthermore, it leads to a generalized improvement in cardiovascular fitness and overall quality of life. The mechanism by which exercise improves outcome in claudicants is complicated and multifactorial. Further research is required in this area to fully elucidate the precise and predominant mechanisms and to assess whether targeted exercise program modification maximizes mechanism efficacy and patient outcome.


Estrogen regulation of testicular function.
Evidence supporting a role for estrogen in male reproductive tract development and function has been collected from rodents and humans. These studies fall into three categories: i) localization of aromatase and the target protein for estrogen (ER-alpha and ER-beta) in tissues of the reproductive tract; ii) analysis of testicular phenotypes in transgenic mice deficient in aromatase, ER-alpha and/or ER-beta gene; and, iii) investigation of the effects of environmental chemicals on male reproduction. Estrogen is thought to have a regulatory role in the testis because estrogen biosynthesis occurs in testicular cells and the absence of ERs caused adverse effects on spermatogenesis and steroidogenesis. Moreover, several chemicals that are present in the environment, designated xenoestrogens because they have the ability to bind and activate ERs, are known to affect testicular gene expression. However, studies of estrogen action are confounded by a number of factors, including the inability to dissociate estrogen-induced activity in the hypothalamus and pituitary from action occurring directly in the testis and expression of more than one ER subtype in estrogen-sensitive tissues. Use of tissue-specific knockout animals and administration of antiestrogens and/or aromatase inhibitors in vivo may generate additional data to advance our understanding of estrogen and estrogen receptor biology in the developing and mature testis.


Chemical analysis and filtration efficiency of ceramic point-of-use water filters.
Ceramic water filters (CWFs) are globally employed as a point-of-use water treatment technology. Although, there are no standards to regulate the use of these CWFs in developing countries, they are gaining acceptability for domestic water treatment. This study sought to assess and compare the efficiency of commercially available types of CWFs and to propose a consumer selection guide for the purchase and use of CWFs. The CWFs selected for the study were, Ball filter with activated carbon (BF + AC), Candle filter (CF), and Pot filter (PFcs) coated with colloidal silver. The elemental and mineral oxide composition of the selected CWFs were analysed with x-ray fluorescence method. Furthermore, the raw unfiltered water (from three different common sources), and the filtrates obtained with the CWFs were analysed for their physicochemical, metal ion removability, and microbial correction. The x-ray fluorescence analysis indicated that Al2O3 and SiO2 were the major mineral oxide compositions of the selected CWFs. These metal oxides were present in varying concentrations. The CWFs showed turbidity reduction of 74.28-99.40%, Mn and Fe reduction of 54.04-98.48% and 48.82-97.50% respectively. In addition, the total coliform reduction by the selected CWFs ranged from 2.31 to 76.97%. It was therefore observed from the results that, the efficiency of commercially available CWFs varied in the order BF + AC > CF > PFcs. BF + AC was the most efficient in both physicochemical and microbial correction of all water sources. CWF selection guide for consumers based on different sources of water which considered the physicochemical parameters, biological parameters and Water Quality Index was discussed. This has an implication for regulation and standardization of CWFs.


Semimicrotitration device for cholinesterase assay.
A semimicrotitration device for reaction volumes of 0.5 to 2 ml and effective stirring of reaction solution or suspension is described. The principal part of the device is a combined glass electrode functioning as a reaction vessel (combined "cup"-glass electrode). Characteristics of the device are small volumes and great reliability. Nonspecific cholinesterase activities measured in rat plasma and liver tissue homogenates and compared with the activities of the same tissue and plasma samples measured radiometrically and spectrophotometrically illustrate the applicability of the device. The method is best suited for kinetic studies with multiple substrates of esterases, either in the soluble form or in tissue homogenates.


Can Workplace Rest Breaks Prevent Work-Related Injuries Related to Long Working Hours?
This study examined the relationship between long working hours, rest breaks, and work-related injuries. A total of 25,439 employees were examined from the 4th Korean Working Conditions Survey. Rest breaks were divided into two groups and working hours were divided into four groups. Multiple logistic regression was conducted to estimate the relationship between long working hours, rest breaks, and work-related injuries. Work-related injuries were significantly associated with long working hours. Stratified by rest breaks, the risk of work-related injuries increased with increasing working hours in a dose-response pattern among those with insufficient rest breaks, while the risk was not significant among those with sufficient rest breaks. It is important to provide sufficient rest breaks to prevent work-related injuries among workers with long working hours.


Uterus transplantation: animal research and human possibilities.
Uterus transplantation research has been conducted toward its introduction in the human as a treatment of absolute uterine-factor infertility, which is considered to be the last frontier to conquer for infertility research. In this review we describe the patient populations that may benefit from uterus transplantation. The animal research on uterus transplantation conducted during the past two decades is summarized, and we describe our views regarding a future research-based human attempt.


[Dehydration in the infant. Revision of 100 cases. Epidemiologic, clinical and biochemical aspects (author's transl)].
A retrospective study of 100 dehydrated children with ages between 0 and 18 months is presented. Ecologic, epidemiologic, clinical and biochemical aspects are revised, as the first part of a series. Relating facts to distribution according with ages and etiology in cases of bacterial diarrhea are similar to other authors. Hypertonic dehydration caused by concentrated nutrition of feeding is prominent, in tight relation with children in low socioeconomically groups. 31% of children had natremia between 150 and 160 mEq/I; and 16% over to 160 mEq/I. Hypocalcemia during rehydration was rarely observed.


Immunohistochemical characterization of nodose cough receptor neurons projecting to the trachea of guinea pigs.
Cough in guinea pigs is mediated in part by capsaicin-insensitive low threshold mechanoreceptors (cough receptors). Functional studies suggest that cough receptors represent a homogeneous population of nodose ganglia-derived sensory neurons. In the present study we set out to characterize the neurochemical profile of cough receptor neurons in the nodose ganglia. Nodose neurons projecting to the guinea pig trachea were retrogradely labeled with fluorogold and processed immunohistochemically for the expression of a variety of transporters (Na+/K+/2C1- co-transporter (NKCC1), alpha1 and alpha3 Na+/K+ ATPase, vesicular glutamate transporters (vGlut)1 and vGlut2), neurotransmitters (substance P, calcitonin gene-related peptide (CGRP), somatostatin, neuronal nitric oxide synthase (nNOS)) and cytosolic proteins (neurofilament, calretinin, calbindin, parvalbumin). Fluorogold labeled ~3 per cent of neurons in the nodose ganglia with an average somal perimeter of 137 +/- 6.2 mum (range 90-200 microm). All traced neurons (and seemingly all nodose neurons) were immunoreactive for NKCC1. Many (> 90 per cent) were also immunoreactive for vGlut2 and neurofilament and between 50 and 85 per cent expressed alpha1 ATPase, alpha3 ATPase or vGlut1. Cough receptor neurons that did not express the above markers could not be differentiated based on somal size, with the exception of neurofilament negative neurons which were significantly smaller (P < 0.05). Less than 10 per cent of fluorogold labeled neurons expressed substance P or CGRP (and these had somal perimeters less than 110 microm) and none expressed somatostatin, calretinin, calbindin or parvalbumin. Two distinct patterns of nNOS labeling was observed in the general population of nodose neurons: most neurons contained cytosolic clusters of moderately intense immunoreactivity whereas less than 10 per cent of neurons displayed uniform intensely fluorescent somal labeling. Less than 3 per cent of the retrogradely traced neurons were intensely fluorescent for nNOS (most showed clusters of nNOS immunoreactivity) and nNOS immunoreactivity was not expressed by cough receptor nerve terminals in the tracheal wall. These data provide further insights into the neurochemistry of nodose cough receptors and suggest that despite their high degree of functional homogeneity, nodose cough receptors subtypes may eventually be distinguished based on neurochemical profile.


Job decision latitude as a potential modifier of the contribution of physical workload to poor functioning in middle-aged employees.
It was hypothesised that job decision latitude may alleviate the detrimental health effect of physical workload. The objective was to test whether job decision latitude modifies the effect of physically demanding work on poor physical functioning, and whether the effects of physically demanding work and job decision latitude are dependent on occupational social class. Data were derived from the Helsinki Health Study baseline questionnaire survey. The participants were employees of the City of Helsinki, Finland, aged 40-60 years. Functioning was measured by Short Form 36 physical component summary. Logistic regression models were used to analyse the data. The hypothesised modification of the effect of physical demands at work on physical functioning by job decision latitude could not be demonstrated. The expected interaction effect was observed only for the semi-professional class, and interaction of physical demands, decision latitude and occupational social class was not statistically significant. Furthermore, the effects of physically demanding work as well as low decision latitude were of similar magnitude in all the occupational social classes. The results suggest that for the majority of employees the effect of physical workload on physical functioning is independent of job decision latitude or occupational social class in general. Control over work conditions is unlikely to reduce difficulties to cope with physical demands, when the actual physical tasks are not changed.


IKK- and NF-κB-mediated functions in carcinogenesis.
Since the initial cloning of RelA and its close relationship to c-Rel, the cellular homolog of the viral oncoprotein v-Rel, the nuclear factor κB (NF-κB) signaling pathway and its upstream activating kinase complex (IκB-kinase) have been suspected to play a major role in tumorigenesis. This was further corroborated by the discovery of oncogenic mutations in NF-κB proteins in certain lymphoid malignancies and the notion that NF-κB is persistently activated in a large variety of solid tumors. With the advent of conditional knockout mice allowing tissue-specific targeting of the various components of the NF-κB signaling pathway, it was possible to genetically test the cell autonomous and non-autonomous functions of NF-κB in inflammation-associated cancer as well as sporadic cancers. Here, we review molecular evidence that demonstrates the various functions of NF-κB during different tumor stages and that supports the rationale to target NF-κB in cancer prevention and therapy.


Genomic analysis of response to traumatic brain injury in a mouse model of Alzheimer's disease (APPsw).
Numerous studies have shown that the beta-amyloid peptide (Abeta) or beta-amyloid deposits impact many processes that can contribute to neurodegeneration, ranging from immune and inflammatory processes to cell death and apoptosis, processes characteristic of both Alzheimer's disease and head injury. Human and animal studies of traumatic brain injury (TBI) have shown that Abeta production is increased acutely following injury, and there is evidence for increased amyloid deposition and risk for Alzheimer's disease following TBI. Given the poorer outcome after injury observed both in transgenic mice overproducing Abeta, as well as in humans subjected to repetitive head injury, one may conclude that the presence of elevated brain levels of Abeta, whether endogenous or as a consequence of previous injury, exacerbates many of the deleterious processes triggered by TBI. We sought to test this hypothesis by examining the genomic response to injury in wild-type mice and in transgenic mice (APPsw) overexpressing and accumulating cerebral Abeta/beta-amyloid. Gene expression was investigated by microarray 24 h after controlled cortical impact (CCI) injury or sham injury in aged APPsw transgenic mice and wild-type controls. Stringent statistical analysis revealed differential expression of a total of 129 genes in the transgenic TBI vs. sham comparison and 119 genes in the wild-type TBI vs. sham comparison. Of these, only 28 genes were common to both comparisons, suggesting considerable differences in response to injury in the Alzheimer models compared to wild-type mice. We focused our analyses by creating a "genotype-dependent" data set of response to injury which contained the genes that were uniquely altered in response to injury in either wild-type or APPsw mice, as well as those which were significantly differently modulated following TBI in one genotype compared to the other. The cellular functions predicted to be influenced by these changes in gene expression thus indicate the adverse pathways triggered by increased levels of Abeta, and the potentially favorable (recovery) pathways which are activated in wild-type mice but suppressed when Abeta levels are high. The results show that the cellular functions most influenced by the cerebral Abeta levels following TBI include inflammation, immune response, and cell death, which suggest a particular vulnerability to head injury in the Alzheimer brain.


Pharmacological treatment in patients with heart failure: patients knowledge and occurrence of polypharmacy, alternative medicine and immunizations.
To evaluate in patients with heart failure (HF) due to systolic dysfunction the occurrence of polypharmacy, alternative medicine, immunization against influenza, and patients' knowledge about their medication. Sixty-five patients, 49 men, mean age 60.5+/-12.0 years answered a confidential questionnaire during 2002. Polypharmacy was frequent, 48 (74%) were taking six or more pills per day and 18 (28%) 11 or more. Fifteen patients (23%) used over-the-counter analgesics. Eight patients (12%) used alternative medicine [five women (31%) vs. three men (6%), P=0.02]. Forty-four patients (68%) received immunization against influenza (18 patients <65 years (54%) vs. 25 patients > or =65 years (79%), P=0.03). Half the patients knew that beta-blockers and vasodilators decreased blood pressure, 31 patients receiving diuretics (88%) knew that this drugs help to eliminate liquids, 12 patients (38%) recognized this effect with low dose spironolactone and 23% or less with other drugs. Only 12 patients (42%) treated with acenocoumarol and 13 of those treated with aspirin (32%) recognized the action of these drugs. Patients with HF and systolic dysfunction have a poor knowledge about the medication they receive. Polypharmacy, over-the-counter, homeopathic and alternative medicine use is frequent whereas the rate of immunization against influenza is low.


Radical cystectomy with or without urethrectomy?
After the introduction of bladder replacement procedures, the indications for prophylactic urethrectomy have become more and more restricted. While years ago, a prophylactic urethrectomy was performed in many patients with cutaneous diversions, it has become clear that only patients with invasion by transitional cell carcinoma at the level of the prostatic urethra or bladder neck have a substantial risk of developing subsequent urethral recurrence. The pre- or intra-operative assessment of the prostatic urethra in males and of the bladder neck in females is the key to appropriate management of the urethra in patients with bladder cancer.


Intracellular picrotoxin blocks pentobarbital-gated Cl- conductance.
Using the 'inside-out' configuration of frog sensory neurons, we studied the effect of intracellular picrotoxin on the pentobarbital-gated single channel response of Cl- -current (iCl). The pentobarbital-induced iCl showed no voltage-dependency and the single channel conductance (gamma Cl) was 16 +/- 3.1 pS (n = 6). Picrotoxin caused the pentobarbital-gated Cl- channels to react in a flickering pattern and then finally caused them to cease their opening altogether. This inhibitory action of picrotoxin was reversible.


Modeling and experimental analyses reveal a two-domain structure and amino acids important for the activity of aminoglycoside resistance methyltransferase Sgm.
Methyltransferases that carry out posttranscriptional N7-methylation of G1405 in 16S rRNA confer bacterial resistance to aminoglycoside antibiotics, including kanamycin and gentamicin. Genes encoding enzymes from this family (hereafter referred to as Arm, for aminoglycoside resistance methyltransferases) have been recently found to spread by horizontal gene transfer between various human pathogens. The knowledge of the Arm protein structure would lay the groundwork for the development of potential resistance inhibitors, which could be used to restore the potential of aminoglycosides to act against the resistant pathogens. We analyzed the sequence-function relationships of Sgm MTase, a member of the Arm family, by limited proteolysis and site-directed and random mutagenesis. We also modeled the structure of Sgm using bioinformatics techniques and used the model to provide a structural context for experimental results. We found that Sgm comprises two domains and we characterized a number of functionally compromised point mutants with substitutions of invariant or conserved residues. Our study provides a low-resolution (residue-level) model of sequence-structure-function relationships in the Arm family of enzymes and reveals the cofactor-binding and substrate-binding sites. These functional regions will be prime targets for further experimental and theoretical studies aimed at defining the reaction mechanism of m7 G1405 methylation, increasing the resolution of the model and developing Arm-specific inhibitors.


Anesthesia in the geriatric patient.
Geriatric anesthesia, or anesthesia in the aged, is no different from anesthesia in younger patients, except that it takes less and lasts longer. Both the anesthesiologist and the surgeon must treat the aged patient with care and gentleness. We must be ever aware that each vital system can be irreparably damaged by our slightest inattention to minute detail. Dr. Harold Griffith once said, "The straw which breaks the camel's back may be a very small one when the camel is nearing the end of its journey."


Autohydrolysis of bamboo (Dendrocalamus giganteus Munro) culm for the production of xylo-oligosaccharides.
Bamboo culm (Dendrocalamus giganteus Munro) was treated with hot water in non-isothermal conditions (140, 160, 180 and 200°C) for various reaction times (10, 30, 60 and 120 min) to generate xylo-oligosaccharides in a batch reactor at a solid to liquor ratio of 1:10 g/g. The influence of reaction conditions on yields, compositions and characteristics of the products were evaluated. The maximum yield of xylo-oligosaccharides of 47.49% was achieved at 180°C for 30 min with a relatively low level of xylose (4.73%) and other products (arabinose 0.20 g/L, galactose 0.19 g/L, HMF 0.15 g/L, furfural 0.36 g/L, acetic acid 0.64 g/L and formic acid 0.26 g/L). Higher temperature and/or longer reaction time reduced the yield of oligosaccharides, and enhanced concentrations of monosaccharides and byproducts. The result demonstrated that the yield of xylo-oligosaccharides obtained by autohydrolysis depends on the reaction temperature and time.


Quick two-dimensional differential in gel electrophoresis-based method to determine length and secondary structures of telomeric DNA.
A novel differential in gel electrophoresis (DIGE)-based method has been developed and applied to measure telomere length and appearance of two-dimensional structural DNA changes. It can be applied to any area requiring quick and evident measurement of structural DNA changes.


Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid.
the aim of this quantitative review is to document potential benefit and adverse effects of hyaluronic acid (HA) injection into the shoulder with rotator cuff tears. a systematic literature search was performed in english PubMed, Medline, Ovid, Google Scholar and Embase databases using the combined key words "hyaluronic acid", "rotator cuff tear", "hyaluronate", "shoulder", "viscosupplementation", with no limit regarding the year of publication. Articles were included if they reported data on clinical and functional outcomes, complications in series of patients who had undergone HA injection for management of rotator cuff tears. Two Authors screened the selected articles for title, abstract and full text in accordance with predefined inclusion and exclusion criteria. The papers were accurately analyzed focusing on objective rating scores reported. a total of 11 studies, prospective, 7 were randomized were included by full text. A total of 1102 patients were evaluated clinically after different HA injection compare with corticosteroid injection, physically therapies, saline solution injection and control groups. The use of HA in patients with rotator cuff tears improve VAS and functional score in all trials that we have analyzed. intra-articular injection with HA is effective in reducing pain and improving function in shoulder with rotator cuff tears and without severe adverse reaction. Level I.


Benzo[a]pyrene--serum : albumin/cysteine interactions: fluorescence and electron spin resonance studies.
The complex between bovine serum albumin (BSA) and benzo[a]pyrene (BaP) exhibits three different types of fluorescence. The visible fluorescence at 407, 431 and 458 nm is modified by the formation of both hydroxy-BaP derivatives and BaP products strongly bound to the protein. The ultraviolet fluorescence I is characterized by a triple-peaked structural fluorescence with maxima at 340, 357 and 378 nm. Upon addition of mercaptoethanol, this ultraviolet fluorescence decreases. The ultraviolet fluorescence II appears at 380 nm and corresponds to that of pyrene-like products. When irradiated with ultraviolet (365 nm) light, both the ultraviolet fluorescence I and the visible fluorescence decreases. In the interactionsof BaP with BSA, a new radical has also been found in addition to the known 6-oxo-BaP radical. The lyophilized BSA-BaP complex exhibits two broad ESR bands, one of which increases in lipid-free BSA. In the concentrated aqueous solution of the BSA-BaP complex, the ESR signal is converted to a six-line spectrum. The benzene extract, which removes non-covalently bound BaP products, shows an ESR signal similar to that in aqueous solution except for the absence of two lower g-valued lines. When irradiated with ultraviolet (365 nm) light the signal intensity of the new radical species decreases, while that of 6-oxo-BaP increases. Upon addition of of mercaptoethanol, the signal of the new radical also diminishes and is replaced by a single narrow signal. Ths mixture of BaP and cysteine kept at room temperature for one day in the dark produces both a six-line ESR spectrum and a broad ultraviolet fluorescence at 330 nm, which gradually decay in about one week. When BaP and cysteine are mixed at 65 degrees C for several hours, little ultraviolet fluorescence and ESR signal are detected. The results indicate the formation of a BaP radical as an intermediate in the interaction of BaP with BSA and cysteine in the presence of oxygen and suggest the involvement of SH-groups in this interaction.


Immediate post-partum insertion of the Antigon.
The results of intrauterine contraception using the Antigon inserted into 364 women immediately post partum are submitted. The patients were followed for 24 months, total number of woman months 5225. The follow-up was 96.7% after 3 months, 92.9% after 12 months, and 89.7% after 24 months. Four types of Antigon were used, having surface areas from 785 to 2740 mm2. Type I and the wing model (type IV), which have the smallest surface area, proved best suited. The continuation rates for types I and IV after 12 and 24 months were 77.4--59.2 and 76.4--54.5 respectively. These rates are on a level with those for Antigon inserted 6--8 weeks post partum. It is notable that the expulsion rates (12.8 and 12.7 after 12 months) were no higher than those for Antigons inserted 6--8 weeks post partum. The incidence of puerperal complications was not increased, and no perforations occurred.


Analysis of the yopA gene encoding the Yop1 virulence determinants of Yersinia spp.
The Yop proteins of Yersinia are important virulence determinants. The Yop1 protein sequences of Yersinia pestis, Yersinia pseudotuberculosis, and two Yersinia enterocolitica serotypes, 0:3 and 0:8, deduced from the nucleotide sequences of the corresponding yopA genes, were compared. Most differences were found in the hydrophilic domains of the proteins, whereas the hydrophobic domains were conserved. The amino acid sequences revealed a signal sequence 25 amino acids long. No cysteine residues were present, even though Yop1 forms a polymeric structure. The transcription startpoint of yopA was determined by primer extension. The coding region and transcription startpoint were separated by a leader sequence 270 nucleotides long. The yopA promoter sequence of Y.pestis is identical to the corresponding sequence of Y. pseudotuberculosis and transcription studies revealed that this promoter is active in Y.pestis. Thus, the inability of Y.pestis to express the Yop1 protein is due to a single base pair deletion in the coding region of the yopA gene of Y.pestis.


Value of age and alarm features for predicting upper gastrointestinal malignancy in patients with dyspepsia: an endoscopic database review of 4664 patients in Thailand.
Age and alarm features are commonly used as indicators for endoscopy in dyspeptic patients; however, the age cut-off and the predictive value of these parameters for identifying upper gastrointestinal (UGI) malignancies are uncertain. Cross-sectional study. Data were extracted from the Gastrointestinal Endoscopy Centre of Siriraj Hospital, Thailand, during 2005-2011. Consecutive patients underwent a first-time upper endoscopy for dyspepsia. Patients with previous surgery, suspected UGI malignancy by imaging, or indefinite biopsy results on prior examination were excluded. Alarm features included dysphagia, unintentional weight loss, GI bleeding/anaemia, and persistent vomiting. The diagnostic performance of each alarm feature and different age cut-off values were evaluated. A total of 4664 patients (mean age: 52.0±14.4 years, 66% female) were included. Alarm symptoms were presented in 21.6%. The prevalence of active Helicobacter pylori infection was 26.3%. Fifty-eight (1.2%) patients had UGI malignancy. The prevalence of malignancy significantly increased with increasing age (0.6% in patients aged <50 years, and 1.8% in patients aged >60 years (p<0.001)). Cancer was found in two patients aged <50 years who did not have alarm features. Patients with alarm features had a higher prevalence of malignancy (OR 22.3, 95% CI 10.5 to 47.4; p<0.001) than those without. The pooled sensitivity, specificity, positive predictive value and negative predictive value of alarm features for UGI malignancy were 87.0%, 79.1%, 4.7% and 99.8%, respectively. Among all age groups, persistent vomiting had a positive likelihood ratio (PLR) >10, while dysphagia and GI bleeding/anaemia had a PLR >10 in patients <50 years old. Despite the overall limited value of age and alarm features, persistent vomiting, dysphagia, and GI bleeding/anaemia are strong predictors for malignancy in patients aged <50 years. Without these symptoms, cancer prevalence is negligible; thus, they are worthy guidance for endoscopic evaluation in this age group.


The Impact of a Vocal Loading Task on Voice Characteristics of Female Speakers With Benign Vocal Fold Lesions.
To examine the effect of a vocal loading task on measures of vocal structure and function in females with benign vocal fold lesions (BVFLs) and determine if change is observed in voice and lesion characteristics. Prospective cohort study. Twenty-eight (n = 28) female subjects with phonotraumatic BVFLs completed a vocal loading task of 30 minutes of reading aloud at 75-85 dBA. Multidimensional voice evaluation was completed pre- and post-load, including audio and videostroboscopy recordings and images for expert perceptual ratings and acoustic and aerodynamic evaluation. Subjects also scored themselves using a 10 cm visual analogue scale for Perceived Phonatory Effort, and completed the Evaluation of Ability to Voice Easily, a 12 item self-report scale of current perceived speaking voice function. An exploratory rather than confirmatory approach to data analysis was adopted. The direction and magnitude of the change scores (pre- to post-load) for each individual, across a wide variety of instrumental and self-report measures, were assessed against a Minimal Clinically Important Difference criteria. Observations of change and the direction of change in vocal response of individuals with BVFLs to 30 minutes of loud vocal load was variable. Minimal to no change was noted for participants pre- to post-load as rated perceptually, for auditory and videostroboscopy samples. For most instrumental measures, change was shown for many participants including an overall improvement in aerodynamic and acoustic measures of function and efficiency post-load for 20 participants (77%) and decline in function for 4 participants (15%). Self-reported effort and vocal function post-load was multidirectional with similar numbers of participants reporting no change, improved function or a decline. Subjects with BVFLs demonstrate change in vocal function following 30 minutes of vocal load. While this change can be variable and multidirectional, overall improvement was observed in instrumental measures of function and efficiency for most participants. Some participants perceived this change to be an increase in effort, some a reduction in effort and some perceived no change. Improved vocal function despite relative lesion stability can seemingly occur after loading in some pathological voices.


The endoplasmic reticulum-Golgi pathway is a target for translocation and aggregation of mutant superoxide dismutase linked to ALS.
Mutations in superoxide dismutase 1 (SOD1) are responsible for 20% cases of familial amyotrophic lateral sclerosis (ALS). However, the mechanism of motor neuron degeneration caused by ALS-linked SOD1 mutants is not fully understood. Here, we used novel live cell imaging techniques to demonstrate the subcellular localization of EGFP-fused SOD1 of both wild-type (WT) and ALS-linked mutant forms in the endoplasmic reticulum (ER) and Golgi. The presence of WT and mutant SOD1 species in luminal structures was further confirmed by immunoblotting analysis of microsomal fractions from spinal cord lysates of SOD1 transgenic mice prepared by sucrose density-gradient ultracentrifugation. Chemical cross-linking studies also revealed an age-dependent aggregation of mutant SOD1, but not of WT SOD1, prominently in the microsomal fraction. Cell-free translocation assays provided evidence that monomeric SOD1 is a molecular form that can be translocated into luminal structures in the presence of ATP. Our finding that the ER-Golgi pathway is a predominant cellular site of aggregation of mutant SOD1 suggests that secretion could play a key role in pathogenesis, which is in line with the view that the disease is non-cell autonomous.


Effects of NFkappaB activation on KSHV latency and lytic reactivation are complex and context-dependent.
Like all herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV) can produce either latent or lytic infection. The latent v-FLIP gene is a strong activator of NFkappaB, and in primary effusion lymphoma (PEL) cells, blockade of NFkappaB activation is associated with enhanced lytic gene expression, while overexpression of p65 impairs expression of reporter genes driven by lytic promoters. This has led to the suggestion that NFkappaB activation may promote latency by suppressing lytic reactivation. Here we examine in detail the effects of NFkappaB activation on KSHV replication in several cell types. In accord with earlier work, we find that inhibition of NFkappaB signaling in PEL cells is associated with enhanced lytic reactivation of KSHV. Similarly, in de novo KSHV infection of primary endothelial cells, inhibition of NFkappaB signaling leads to an increase in lytic gene expression and enhanced virion production. By contrast, KSHV-infected human foreskin fibroblasts (HFF) show no increase in spontaneous lytic reactivation when NFkappaB is inhibited. Moreover, if NFkappaB activation is always inhibitory to lytic gene expression, one might expect its activation to be suppressed during the lytic cycle. However, we find that NFkappaB signaling is strongly and consistently activated in lytically infected cells of all lineages. Together these data indicate that (i) the relationship of NFkappaB activation to latency and lytic reactivation is not uniform, but is dependent on the cellular context; and (ii) even though NFkappaB activation is inhibitory to lytic gene expression in some contexts, such inhibition is at least partially bypassed or overridden during lytic growth.


[Results of sacral posterior neuromodulation on voiding disorders and impact on sexuality based on a single-center study].
The objective of this study was to evaluate the results of S3 sacral neuromodulation on certain voiding disorders (overactive bladder and chronic retention) and its impact on the sexuality of these patients. A S3 sacral root neuromodulator was implanted in 41 patients with a mean of age of 53 years between January 1999 and March 2004. This study comprised two groups: one group composed of patients with overactive bladder (32 subjects) and the other composed of patients with chronic retention without obstruction (nine subjects). The mean follow-up of this study was 34 months (range: 12 to 72 months). In the group of patients with overactive bladder, after the operation, the daily voiding frequency decreased from 20.8 to 7.8 (p<0.0001), episodes of incontinence decreased from 3.7 to 1.4 per day (p<0.0001), the number of pads decreased from 2.5 to 1 per day (p<0.001) and 72% of these patients reported an improvement of their continence time. In the group with chronic retention, the number of intermittent self-catheterizations decreased from 4.77 to 0.44 per day (p=0.0169) and 72% of these patients resumed spontaneous voiding (7/9). Among this patient population, 41.5% reported sexual problems, which were improved after implantation of the neurostimulator in 41.2% of cases. In the light of these results, sacral neuromodulation appears to be an effective treatment for certain refractory chronic voiding disorders such as overactive bladder and chronic retention without obstructive syndrome. This study showed that improvement of clinical signs could have a positive impact on the sexuality of these patients, especially for patients with chronic retention without obstruction.


Prognostic significance of the absence of normal septal Q waves before aortic valve replacement.
Aim of this study was to investigate the prognostic significance of absence of septal Q waves in patients scheduled for aortic valve replacement. Sixty-one patients who underwent isolated aortic valve replacement for aortic stenosis were retrospectively evaluated. Septal Q waves were defined as Q waves of<2mm in amplitude and<40ms in width and absence of septal Q waves was defined as simultaneous loss of Q waves from at least three of the leads I, aVL, V5 and V6. Septal Q waves were absent in 17 patients (Group AQ, 27.8%) and were present in 44 patients (Group PQ, 72.1 %) preoperatively. Newly developed AV block>1st degree and newly developed left bundle branch block were primary endpoints. Preoperatively, absence of normal septal Q waves was significantly associated with increased risk of postoperative AV block (HR: 11.18, range 1.37-91.21, 95% CI, p=0.02) whereas it was not associated with increased risk for newly developed LBBB (HR: 3.15 0.62-15.83, 95% CI, p=0.16). Absence of normal septal Q waves in the preoperative ECG may predict further delay in conduction which might develop in the early postoperative course of aortic valve replacement.


Comparative histopathologic study of various lens biomaterials in primates after Nd:YAG laser treatment.
A Nd:YAG laser was used to perform posterior capsulotomies on primates in whom one-piece silicone or three-piece polymethylmethacrylate intraocular lenses were in place for more than one year. The eyes were followed for eight weeks after treatment before enucleation. Histologically, no toxic effects caused by the dispersion of any of the biomaterial within the eyes and no significant inflammatory reactions were seen. The silicone lenses used in this study compared favorably with traditional polymethylmethacrylate lenses when posterior capsulotomies with a Nd:YAG laser were performed.


National Partnership for Maternal Safety: Consensus Bundle on Support After a Severe Maternal Event.
Supporting women, families, and clinicians with information, emotional support, and health care resources should be part of an institutional response after a severe maternal event. A multidisciplinary approach is needed for an effective response during and after the event. As a member of the maternity care team, the nurse's role includes coordination, documentation, and ensuring patient safety in emergency situations. The National Partnership for Maternal Safety, under the guidance of the Council on Patient Safety in Women's Health Care, has developed interprofessional work groups to develop safety bundles on diverse topics. This article provides the rationale and supporting evidence for the support after a severe maternal event bundle, which includes structure- and evidence-based resources for women, families, and maternity care providers. The bundle is organized into four domains: Readiness, Recognition, Response, and Reporting and Systems Learning, and it may be adapted by nurses and multidisciplinary leaders in birthing facilities for implementation as a standardized approach to providing support for everyone involved in a severe maternal event.


Mega-oss and Mega-TCP versus Bio-Oss granules fixed by alginate gel for bone regeneration.
Bone graft materials are widely used at present because inadequate bone volume is usually found in implant patients. To determine the biocompatibility of a new grafting material, in vitro research is routinely performed before animal experiments and clinical testing. However, during in vitro experiments, bone material particles might move during testing, which could affect the accuracy of the results. To evaluate the biocompatibility of new bone substitutes, Mega-oss and Mega-TCP were compared with Bio-Oss using osteoblast cells and osteoclast cells fixed with alginate gel. Cell morphology, viability, bone resorption, alkaline phosphatase (ALP) activity, and staining were tested to compare the biocompatibility differences in the performance of Mega-oss, Mega-TCP, and Bio-Oss. Cells spread better on Mega-oss and Mega-TCP than the round shape on Bio-Oss. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) results showed that Mega-oss, Mega-TCP, and sodium alginate had good viability. Meanwhile, Mega-oss and Mega-TCP had the same osteoblast differentiation ability as Bio-Oss. The resorption rates of Mega-TCP and Mega-oss were higher than those of Bio-Oss (24.4%, 15.3%, and 3.3%, respectively). Mega-oss and Mega-TCP might be useful alternative bone graft materials compared with Bio-Oss. In addition, fixing the materials with sodium alginate gel could be a new method for in vitro bone material experiments.


Automatic Extraction of Comprehensive Drug Safety Information from Adverse Drug Event Narratives in the Korea Adverse Event Reporting System Using Natural Language Processing Techniques.
Concerns have been raised over the quality of drug safety information, particularly data completeness, collected through spontaneous reporting systems (SRS), although regulatory agencies routinely use SRS data to guide their pharmacovigilance programs. We expected that collecting additional drug safety information from adverse event (ADE) narratives and incorporating it into the SRS database would improve data completeness. The aims of this study were to define the extraction of comprehensive drug safety information from ADE narratives reported through the Korea Adverse Event Reporting System (KAERS) as natural language processing (NLP) tasks and to provide baseline models for the defined tasks. This study used ADE narratives and structured drug safety information from individual case safety reports (ICSRs) reported through KAERS between 1 January 2015 and 31 December 2019. We developed the annotation guideline for the extraction of comprehensive drug safety information from ADE narratives based on the International Conference on Harmonisation (ICH) E2B(R3) guideline and manually annotated 3723 ADE narratives. Then, we developed a domain-specific Korean Bidirectional Encoder Representations from Transformers (KAERS-BERT) model using 1.2 million ADE narratives in KAERS and provided baseline models for the task we defined. In addition, we performed an ablation experiment to investigate whether named entity recognition (NER) models were improved when a training dataset contained more diverse ADE narratives. We defined 21 types of word entities, six types of entity labels, and 49 types of relations to formulate the extraction of comprehensive drug safety information as NLP tasks. We obtained a total of 86,750 entities, 81,828 entity labels, and 45,107 relations from manually annotated ADE narratives. The KAERS-BERT model achieved F1-scores of 83.81 and 76.62% on the NER and sentence extraction tasks, respectively, while outperforming other baseline models on all the NLP tasks we defined except the sentence extraction task. Finally, utilizing the NER model for extracting drug safety information from ADE narratives resulted in an average increase of 3.24% in data completeness for KAERS structured data fields. We formulated the extraction of comprehensive drug safety information from ADE narratives as NLP tasks and developed the annotated corpus and strong baseline models for the tasks. The annotated corpus and models for extracting comprehensive drug safety information can improve the data quality of an SRS database.


Inhibitory effects of TTP sera on binding of anti-platelet glycoprotein IIb-IIIa monoclonal antibodies to human vascular endothelial cells.
The binding of anti-human platelet glycoprotein (GP) IIbIIIa monoclonal antibodies to human umbilical vein endothelial cells (HUVE) was studied. Scatchard analysis using 125I-anti-platelet GPIIb-IIIa monoclonal antibody showed that the maximum binding capacity (B max) was 8 X 10(4)/cell and Kd was 40.2 nM. The binding rate of 125I-anti-platelet GPIIbIIIa monoclonal antibodies to HUVE treated with TTP sera was 11.6 +/- 2.8%, compared with the 24.0 +/- 7.5% observed for HUVE treated with normal sera. These findings showed that there are GPIIb-IIIa on HUVE and that TTP sera may contain anti-platelet GPIIbIIIa antibodies.


Hindfoot salvage with external fixation.
Hindfoot salvage procedures by definition present circumstances requiring extraordinary measures to prevent or limit damage or destruction. Although this technique is used at some centers as the only means of correcting and fixating foot and ankle deformities, it is an expensive procedure. Other available methods may be more expeditious depending on the circumstances. However, the benefits of external fixation in certain circumstances are invaluable. Circular frame external fixators are important tool for the foot and ankle surgeon.


Dietary polyphenols: focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis.
Plants continuously produce an extraordinary variety of biologically active low-molecular-mass compounds. Among them, resveratrol (3,5,4'-trihydroxystilbene) is endowed with significant positive activities by protecting against cardiovascular diseases and preventing the development and progression of atherosclerosis. Furthermore, the molecule significantly ameliorates glucose homeostasis in obese mice. These beneficial effects have driven considerable interest towards resveratrol molecular activities, and intensive efforts for the identification of the stilbene targets have been made. The molecule shows a pleiotropic mode of action. Particularly, its cellular targets are crucial for cell proliferation and differentiation, apoptosis, antioxidant defence and mitochondrial energy production. The complexity of resveratrol activities might account for its effectiveness in ameliorating multifactorial processes, including the onset and/or progression of several degenerative diseases such as myocardial infarction, atherosclerosis and type 2 diabetes. This article reports the actions of resveratrol on cardiovascular diseases and the molecular bases of its activity. We also discuss recent data on the effect of resveratrol on glucose homeostasis and obesity. Finally, the relevance of the stilbene use in the development of new pharmacological strategies is evaluated.


Extra-osseous localisation of 99Tcm methylene diphosphonic acid (MDP) in a primary neuroblastoma.
A case of primary neuroblastoma in a seven year old boy is presented in which 99Tcm methylene diphosphonic acid (MDP) used as a bone scanning agent localised in the primary tumour. The possible mechanism for this is discussed.


Solar-driven water-splitting provides a solution to the energy problem underpinning climate change.
The emergence of the oxygen-evolving photosystem two complex over 2.6 billion years ago represented the 'big bang of evolution' on planet Earth. It allowed phototrophic organisms to use sun light as an energy source to extract electrons and protons from water, and concomitantly release oxygen. Oxygenic photosynthesis not only created an aerobic atmosphere but also removed CO2 to produce the organic molecules that make up the current global biomass and fossil fuel. In addition, it paved the way for animal life. Today extensive burning of fossil fuels is reversing the results of photosynthesis through billions of years, rapidly releasing CO2 back into the atmosphere and consequently increasing the temperature of the planet. There is an urgent need to develop new sustainable energy sources, but the choice is not obvious. My approach to this problem has been to unravel the blueprint of photosystem II (PSII) and to develop an 'Artificial Leaf' technology. A significant step with respect to that mission was achieved at Imperial College when we could conclude from X-ray diffraction of PSII crystals, that the water-splitting catalytic centre consists of a unique Mn3Ca2+O4 cubane structure with a fourth dangler Mn oxo-bonded to the cubane. Here I use this and more recent structures to discuss the mechanism of water splitting and O-O bond formation. Furthermore, I will address how this information can be used to design novel water-splitting catalysts and highlight recent progress in this direction. My conviction is 'if plants can do it, we can do it - after all it is all about chemistry'.


Dispensing medications without prescription at Saudi community pharmacy: Extent and perception.
To investigate the dispensing behavior of pharmacists in retail pharmacy practice and to assess their attitude toward dispensing non-OTC drugs and scrutinize the causes of their malpractice; if in fact was perceived. Between December 2010 and January 2011 retail pharmacies in Jeddah-KSA were visited randomly by a number of voluntary collaborators who played the role of asking for one or more of the following medications without providing a prescription: Co-amoxiclav (Augmentin) or Cefaclor (Ceclor), Captopril (Capoten) and Fluoxetine (Prozac). A total of 60 pharmacies were randomly included in this study; 100% of the pharmacists working were male, 96.7% of them were non-Saudis and only 2 (3.3%) were Saudis. In a total of 119 drug requests, almost all pharmacists (97.9%) handed out the antibiotic immediately, 100% dispensed captopril and 89.5% gave the antipsychotic simply by following the collaborator's request without even asking for a doctor's prescription. In the second part of the study (where a mini-questionnaire is administered), 85% of the pharmacists agreed to answer the mini-questionnaire, and 15% refused to participate. The highest reason given for their wrongdoing, was for that if the pharmacist did not, others - of neighboring pharmacies - would do the same, followed by that there is no available OTC list. The study confirmed that pharmacists are still violating the law, which is leading to a profound malpractice in retail pharmacies around the country. Consequently, regulations should be reviewed and structured educational campaigns are a must to both pharmacists and public. The OTC list should be generated, implemented, and monitored by Saudi regulators and penalize violators.


A new lectin from the floral capitula of Egletes viscosa (EgviL): Biochemical and biophysical characterization and cytotoxicity to human cancer cells.
Egletes viscosa is a plant with therapeutic value due to its antibacterial, antinociceptive and gastroprotective properties. This study aimed to purify, characterize, and evaluate the cytotoxicity of a lectin (EgviL) from the floral capitula of E. viscosa. The lectin was isolated from saline extract through precipitation with ammonium sulfate followed by Sephadex G-75 chromatography. The molecular mass and isoelectric point (pI) of EgviL were determined as well as its temperature and pH stability. Physical-chemical parameters of interaction between EgviL and carbohydrates were investigated by fluorescence quenching and 1H nuclear magnetic resonance (NMR). Cytotoxicity was investigated against human peripheral blood mononuclear cells (PBMCs) and neoplastic cells. EgviL (28.8 kDa, pI 5.4) showed hemagglutinating activity stable towards heating until 60 °C and at the pH range 5.0-7.0. This lectin is able to interact through hydrophobic and electrostatic bonds with galactose and glucose, respectively. EgviL reduced the viability of PBMCs only at the highest concentration tested (100 μg/mL) while was toxic to Jurkat E6-1 cells with IC50 of 24.1 μg/mL,inducing apoptosis. In summary, EgviL is a galactose/glucose-binding protein with acidic character, stable to heating and with cytotoxic effect on leukemic cells.


Cell-sheet technology combined with a thienoindazole derivative small compound TD-198946 for cartilage regeneration.
Articular cartilage is a permanent tissue, with poor self-regenerative capacity. Consequently, a tissue engineering approach to cartilage regenerative therapy could greatly advance the current treatment options for patients with cartilage degeneration and/or defects. A successful tissue engineering approach would require not only induction of chondrogenic differentiation, but also suppression of subsequent endochondral ossification and chondrocyte dedifferentiation. We previously reported that direct injection of the thienoindazole derivative, TD-198946, into the knee joints of mice halted the progression of osteoarthritis; the compound induced chondrogenic differentiation without promoting endochondral ossification. In the present study, we applied TD-198946 to a cell-based cartilage reconstruction model, taking advantage of the cell-sheet technology. Cartilaginous cell-sheets were generated by culturing mouse and canine costal chondrocytes and human mesenchymal stem cells with TD-198946 on temperature-responsive dishes. The transplanted cell-sheets were then successfully used to promote the reconstruction of permanent cartilage, with no evidence of chondrocyte hypertrophy in the knee articular cartilage defects created in mice and canines. Thus, TD-198946 is a promising candidate for cell-based cartilage reconstruction therapies, enabling us to avoid any concern surrounding the use of scaffolds or cytokines to stimulate regeneration.


The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy.
While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established. To evaluate the association of PBT with disease recurrence and mortality following RC. We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization. Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables. A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range [IQR]: 2-4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p<0.0001), had a worse Eastern Cooperative Oncology Group performance status (p<0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p = 0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9-15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p = 0.01), cancer-specific survival (59% vs 72%; p<0.001), and overall survival (45% vs 63%; p<0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio [HR]: 1.20; p = 0.04), death from BCa (HR: 1.31; p = 0.003), and all-cause mortality (HR: 1.27; p = 0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p<0.0001) and all-cause mortality (HR: 1.05; p<0.0001). Limitations include selection bias and lack of standardized transfusion criteria. We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted.


Selection of single-chain antibodies that specifically interact with vesicular stomatitis virus (VSV) nucleocapsid and inhibit viral RNA synthesis.
The RNA genome of non-segmented negative-strand RNA viruses is completely covered by the nucleoprotein (N) forming a ribonucleoprotein complex, the nucleocapsid. The nucleocapsid functions as the template for viral RNA synthesis that is mediated by a viral RNA-dependent RNA polymerase. It is postulated that the selection of molecules that would specifically target the nucleocapsid and thus inhibit the viral polymerase activity could represent a common approach to block negative-strand RNA viruses. Two single-chain antibody fragments (scFv) that were selected using the phage display technology and interacted specifically with vesicular stomatitis virus (VSV) nucleocapsid were characterized. The two recombinant antibodies recognize a conformational epitope on the nucleocapsid and immunoprecipitate specifically nucleocapsids from infected cell extracts. Both antibodies have a strong inhibitory effect on VSV transcription activity in vitro. Thus, they represent starting molecules for future development of in vivo viral RNA synthesis inhibitors.


Identifying potential indicators to measure the outcome of translational cancer research: a mixed methods approach.
In a context where there is an increasing demand to evaluate the outcome of bio-medical research, our work aims to develop a set of indicators to measure the impact of translational cancer research. The objective of our study was to explore the scope and issues of translational research relevant to evaluation, explore the views of researchers on the evaluation of oncological translational research, and select indicators measuring the outcomes and outputs of translational research in oncology by consensus. Semi-structured interviews amongst 23 researchers involved in translational cancer research were conducted and analysed using thematic analysis. A two-round modified Delphi survey of 35 participants with similar characteristics was then performed followed by a physical meeting. Participants rated the feasibility and validity of 60 indicators. The physical meeting was held to discuss the methodology of the new indicators. The main themes emerging from the interviews included a common definition for translational research but disagreements about the exact scope and limits of this research, the importance of multidisciplinarity and collaboration for the success of translational research, the disadvantages that translational research faces in current evaluation systems, the relative lack of pertinence of existing indicators, and propositions to measure translational cancer research in terms of clinical applications and patient outcomes. A total of 35 participants took part in the first round survey and 12 in the second round. The two-round survey helped us select a set of 18 indicators, including four that seemed to be particularly adapted to measure translational cancer research impact on health service research (number of biomarkers identified, generation of clinical guidelines, citation of research in clinical guidelines, and citation of research in public health guidelines). The feedback from participants helped refine the methodology and definition of indicators not commonly used. Indicators need to be accepted by stakeholders under evaluation. This study helped the selection and refinement of indicators considered as the most relevant by researchers in translational cancer research. The feasibility and validity of those indicators will be tested in a scientometric study.


Auto ADP-ribosylation of NarE, a Neisseria meningitidis ADP-ribosyltransferase, regulates its catalytic activities.
NarE is an arginine-specific mono-ADP-ribosyltransferase identified in Neisseria meningitidis that requires the presence of iron in a structured cluster for its enzymatic activities. In this study, we show that NarE can perform auto-ADP-ribosylation. This automodification occurred in a time- and NAD-concentration-dependent manner; was inhibited by novobiocin, an ADP-ribosyltransferase inhibitor; and did not occur when NarE was heat inactivated. No reduction in incorporation was evidenced in the presence of high concentrations of ATP, GTP, ADP-ribose, or nicotinamide, which inhibits NAD-glycohydrolase, impeding the formation of free ADP-ribose. Based on the electrophoretic profile of NarE on auto-ADP-ribosylation and on the results of mutagenesis and mass spectrometry analysis, the auto-ADP-ribosylation appeared to be restricted to the addition of a single ADP-ribose. Chemical stability experiments showed that the ADP-ribosyl linkage was sensitive to hydroxylamine, which breaks ADP-ribose-arginine bonds. Site-directed mutagenesis suggested that the auto-ADP-ribosylation site occurred preferentially on the R(7) residue, which is located in the region I of the ADP-ribosyltransferase family. After auto-ADP-ribosylation, NarE showed a reduction in ADP-ribosyltransferase activity, while NAD-glycohydrolase activity was increased. Overall, our findings provide evidence for a novel intramolecular mechanism used by NarE to regulate its enzymatic activities.


Saturable absorber Co2+:MgAl2O4 crystal for Q switching of 1.34-microm Nd3+:YAlO 3 and 1.54-microm Er3+:glass Lasers.
Saturable-absorber Q switching of a neodymium-doped YAlO(3) laser at 1.34 microm and an erbium-doped glass laser at 1.54 microm with a Co(2+):MgAl(2)O(4) crystal was demonstrated. Q-switched 1.34-microm pulses of 19-mJ energy and 60-ns duration and Q-switched 1.54-microm pulses of 2.7-mJ energy and 75-ns width were obtained. The ground-state absorption cross sections of the Co(2+):MgAl(2)O(4) crystal were estimated to be (2.8 +/- 0.4) x 10(-19) and (3.5 +/- 0.6) x 10(-19) cm(2) at 1.34 and 1.54 microm, respectively. The (4)T(1)((4)F)-->(4)A(2) relaxation time of the Co(2+) ion in the MgAl(2)O(4) crystal was measured to be approximately 350 ns.


Pulmonary Manifestations of Immunodeficiency and Immunosuppressive Diseases Other than Human Immunodeficiency Virus.
Immune deficiencies may alter normal lung function and protective mechanisms, resulting in a myriad of pulmonary manifestations. Primary immunodeficiencies involve multiple branches of the immune system, and defects may predispose to recurrent upper and lower respiratory infections by common pathogens; opportunistic infections; and autoimmune, inflammatory, and malignant processes that may result in interstitial pneumonias. Secondary immunodeficiencies may result from neoplasms or their treatment, organ transplant and immunosuppression, and from autoimmune diseases and their treatments. Primary and secondary immunodeficiencies and their pulmonary manifestations may be difficult to diagnose and treat. A multidisciplinary approach to evaluation is essential.


Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism.
Sleep-disordered breathing (SDB) may trigger thromboembolic events by enhancing intravascular clot formation. The primary objective of the present nested case-control study was to investigate whether the prevalence of SDB is increased in patients with deep vein thrombosis (DVT) and/or acute pulmonary embolism (PE). 82 consecutive patients with DVT and/or PE (cases) were prospectively enrolled irrespective of SDB-related symptoms and formed matched pairs with patients without DVT and/or PE (controls) according to sex and pre-defined categories of age and body mass index. The prevalence of SDB (respiratory disturbance index assessed by polygraphy ≥ 15 events·h(-1)) was significantly greater in the cases with DVT and/or PE than in controls (40 versus 26%, p=0.046) and was predominantly obstructive in nature. Multiple regression analysis revealed that SDB was significantly associated with DVT and/or PE (OR 2.28, 95% CI 1.08-4.85; p=0.032) independent of established risk factors for thrombosis. In the sex-specific analyses this association was significant in females (OR 4.14, 95% CI 1.05-16.36; p=0.042), but not in males (OR 1.55, 95% CI 0.57-4.21; p=0.391). SDB occurs more frequently in females with DVT and/or PE than in controls matched for anthropometric variables, and is independently associated with the occurrence of these thromboembolic events.


Medicolegal aspect of loss of smell and olfactory event-related potentials.
It is not straightforward to objectively evaluate the olfactory dysfunction that occurs following forensic incidents. The olfactory event-related potentials method, based on electrophysiological records, may provide objective data in the evaluation of posttraumatic anosmia cases from the medicolegal perspective. This study, where a quantitative evaluation of the cases with the complaints of olfactory sensation disorder was performed using the olfactory event-related potentials test, aims to identify the factors that should be considered in the evaluation of olfactory dysfunction from the medicolegal perspective. This study first evaluated the complaints of 98 patients admitted because of posttraumatic impaired smell and then administered electrophysiological odor tests on the patients. Because of this, the relationship between the EEG responses of the cases and the olfactory disorder was examined. Of the 98 cases that participated in the study, 68 (69.4%) were male and 30 (30.6%) were female. Of all cases, 53 (54.1%) had complaints of not being able to smell at all, 14 (14.3%) had complaints of reduced smell, whereas, in addition to the existing complaints of olfactory dysfunction, 44 (44.9%) of them had complaints of taste perception and 18 (18.3%) reported having vision disorders. 21 of 37 cases who reported being unable to smell during the test turned out to be anosmic. Furthermore, 16 cases stated that, though having had a response in the odor test, they had no sense of smell following the test. Although it seems possible to prove that there is a relationship between the olfactory event-related potential test and the diagnosis of anosmia, there is still ongoing research on its use in clinical practice. Performing both subjective and electrophysiological tests together to detect olfactory dysfunctions that occur after a forensic incident enable provide more reliable results in diagnosis.


The structure of a reduced mutant T4 glutaredoxin.
The mutant T4 glutaredoxin where the active site residues Val15 and Tyr16 have been substituted by Gly and Pro, respectively, crystallizes in a form where the active site disulfide is accessible to reagents. Treatment of the crystals with dithiotreitol causes very subtle changes in the overall glutaredoxin structure. The main differences are seen around the active site where the sulfurs of Cys14 and Cys17 move apart slightly.


Prevalence, incidence and mortality of hypertrophic cardiomyopathy based on a population cohort of 21.9 million in China.
There are limited studies on the prevalence and incidence of clinically diagnosed hypertrophic myocardiopathy (HCM) and its mortality in the Chinese population, and the projected population burden of HCM over the next decades. We collected data on HCM and its mortality from the Beijing Municipal Health Commission Information Center (BMHCIC) database and estimated the prevalence and incidence based on the whole Beijing population. Calculation of population trends was performed using annual percentage change (APC) and average annual percentage change (AAPC). Finally, future HCM incidence was built by modelling projection of HCM to the next decades using Poisson regression analysis and Gray Model 1,1(GM [1,1]). The prevalence of HCM was 0.0069% (95%CI, 0.0065-0.0072%; N = 1343) in 2010, rising to 0.076% (95% CI, 0.074-0.077%; N = 16,616) in 2019, and the incidence of HCM was 6.85 per 100 000 person-year in 2010, rising to 11.76 per 100 000 person-year in 2019. Males had higher prevalence and incidence of HCM than females. The APPC for the rising incidence of HCM was 5.8% and the expected numbers will double increase in 2029 by assuming the same increase trend as the last decades. HCM had increased annual incidence of HF (APPC: 8.4, 4.4-12.6, p < 0.05), and relatively stable annual incidence of mortality (APPC: 1.2%, - 2.3% to 4.8%, p > 0.05) during the studied period. Males had lower mortality (2.70% vs. 4.20%, p < 0.001) than females. The calculated HCM prevalence was much lower compared to prior screening studies from 2004, although the predicted HCM incidence would double over the next decades. HCM was associated with a stable risk of mortality during the studied period.


Evaluation of a new ambulatory blood pressure device.
We assessed the OSCILL-IT ambulatory blood pressure (BP) recorder (FIGI sr1, Rome, Italy) according to the performance criteria set out by the British Hypertension Society (BHS) protocol. The OSCILL-IT is a portable, noninvasive recorder that uses a process that correlates systolic, mean, and diastolic areas, identified on the oscillations, to the cuff absolute pressure. According to the recommendations of BHS, a large heterogeneous population (100 subjects: 52 men aged from 19 to 79--median 44 and 48 women from 19 to 74--median 54) was recruited in order to assess accuracy and to analyze, in addition, the effects of observer agreement and BP level on the observer-device differences. With reference to BP level, we suggest also a new graphic approach. Four sets of sequential, same arm, comparative BP measurements were obtained, performed by the OSCILL-IT recorder and two skilled clinicians using a mercury column, for each subject. We used a linear combination for the statistical evaluations. We confirmed the observer agreement through the frequency distribution of BP as a function of the observer and through the differences between observers. We compared OSCILL-IT with sphygmomanometric readings: the differences were not significant. A visual inspection, with the addition of regression lines, showed that there were no variations in differences at the changing of BP level. The difference between observers and OSCILL-IT was 0.2 +/- 5.3 mm Hg and 0.2 +/- 5.8 mm Hg both for systolic BP (SBP) and diastolic BP (DBP). The level of agreement, according to BHS criteria, showed that 64% of all systolic and 70% of all diastolic readings obtained by the OSCILL-IT were within 5 mm Hg of the sphygmomanometric determinations. Therefore, the grade is C for SBP, even if 93% of SBP and 95% of DBP obtained by the OSCILL-IT were within 10 mm Hg of the sphygmomanometric determinations. These analyses demonstrate that the OSCILL-IT satisfies the accuracy parameters and the additional linear regression yields graphics more immediate.


How has the COVID-19 pandemic influenced nursing students' academic experience and career choices? A qualitative descriptive analysis.
COVID-19 control measures influenced education and training environments and profoundly impacted nursing students' career prospects and academic lives. This study intends to elucidate the impact of the COVID-19 pandemic on nursing students' academic experience and career choices. A qualitative descriptive study was conducted at a 4-year university in Japan, using semi-structured interviews with 14 nursing students. Sandelowski's qualitative descriptive analysis was conducted. We identified 11 categories that summarize COVID-19's influence on students' academic experience and career choices: "Forced change to a new learning system," "Difficult learning thoroughly with restricted face-to-face interactions," "Worries regarding teacher evaluations when face-to-face interactions are restricted," "Adapting to changes in the learning environment," "Finding new ways to learn due to the different learning environment," "Worries regarding career decision-making after losing opportunities to obtain career information," "Fully utilizing limited information resources in deciding where to work while being influenced by others," "Coping with a confusing new job hunting system," "Worries about becoming a nurse without enough practical experience," "Conscious of working as a nurse while facing infections," and "Support from those around me is helpful in an unfamiliar environment." The categories comprised four elements: academic impact, employment/career impact, future impact on working as a nurse, and environmental support. Building an online education/training program, ensuring the availability of regular psychological support, providing abundant information on employment, installing an information desk, and providing regular feedback were considered imperative for supporting nursing students.


Epstein-Barr virus vaccines.
Epstein-Barr virus (EBV) is a human viral pathogen of considerable importance. More than 95% of the human population world-wide becomes infected with the virus during childhood, although in the West infection may be delayed until adolescence. The infection only has an undesirable significant clinical outcome in a tiny minority of cases, but because the virus is so ubiquitous the minority is numerically very significant. The virus is associated with two important human cancers, endemic Burkitt's lymphoma (BL) and undifferentiated nasopharyngeal carcinoma (NPC). These diseases have a very clearly defined geographical distribution in the Third World indicating a strong co-factor dependence. In the West, Epstein-Barr virus infection, when delayed to adolescence, is associated with infectious mononucleosis. The virus is also associated in the West with tumours arising in individuals undergoing immunosuppressive treatment or who are immunosuppressed as a result of HIV infection. More recently evidence has been obtained of an association with Hodgkin's disease which is very common in the West. A number of vaccines have been developed based on the EBV envelope glycoprotein gp340. Vaccination of those populations at risk from developing NPC or BL should lead to a reduction or elimination of these diseases. A safe and effective vaccine may also have a role in the prevention of EBV-related diseases in the West. Recombinant vaccinia, varicella and adenovirus vaccine vectors expressing gp340 are being developed and a recombinant-derived subunit vaccine based on the gp340 molecule is shortly to enter phase I human trials.


Anaesthetic management of emergency caesarean section in a patient with seizures and likely raised intracranial pressure due to tuberculous meningitis.
We report the anaesthetic management of a term pregnant woman with active tuberculous meningitis, who had experienced seizures, had signs of raised intracranial pressure and required emergency caesarean section. Peripartum anaesthetic management of a patient with tuberculous meningitis is a rare event.


Embryotoxicity and in vivo cytogenetic changes following maternal exposure to cadmium chloride in mice.
Cadmium is a well-known teratogen in laboratory animals and a widespread environmental pollutant. The frequencies of sister chromatid exchanges (SCEs), nucleolar organizing regions (NORs) and chromosomal aberrations were analysed in maternal bone marrow and fetal liver and/or lung cells of mice, following maternal treatment with cadmium chloride, on gestational days 8 through 10. The embryotoxic effects and morphological changes on day 18 fetuses were also studied. Cadmium chloride is readily transferred across the placenta and significant levels were detected in both the placenta and fetus. No significant changes in the frequencies of SCEs or NORs in maternal and fetal cells were observed following exposure to cadmium chloride. Fetal tissues showed mitotic inhibition at the highest dose levels (8.4 and 11.4 mg/kg, b.w.). Maternal treatment with cadmium chloride increased embryonic resorptions and fetal lethality, as well as reduced placental weight; however, it did not produce significant chromosomal changes except at the highest dose level (11.4 mg/kg).