Epstein-Barr virus infection of HIV-seropositive individuals is transiently suppressed by high-dose acyclovir treatment.
To assess whether oral acyclovir can eliminate persistent Epstein-Barr virus (EBV) infection and thereby prevent EBV-associated lymphoma development in HIV-seropositive homosexual men. Persistent EBV infection was examined in a group of 21 HIV-seropositive homosexual men before, during and after treatment with oral acyclovir at a dose of 800 mg every 6 h (10 individuals) or with a placebo (11 individuals). In 13 individuals, EBV was isolated from the oropharynx before and after treatment (seven cases from the acyclovir-treated group and six from the placebo-treated group). A significant reduction in virus isolation occurred during treatment in the acyclovir-treated group, but not in the placebo-treated group. In seven cases in whom EBV shedding was detected before and after treatment, the EBV strain isolated was identical throughout the study, even when acyclovir had abolished detectable shedding for the duration of the treatment. In two other cases more than one strain was detected. On examination of the EBV type present, 89% of a group of 18 patients consistently shed type A virus, 5.5% type B virus and 5.5% showed evidence of co-infection with both virus types. This compares with figures of 100, 0 and 0%, respectively, in a control group of HIV-seronegative individuals. High-dose acyclovir therapy does not eliminate persistent EBV infection from the oropharynx of healthy HIV-seropositive individuals and therefore would not necessarily prevent lymphoma development. Our results suggest that infection by type B EBV, and co-infections of both A and B type, are more common in HIV-seropositives than HIV-seronegatives.


Factors associated with post-stroke depression in the acute phase of ischemic stroke: A cross-sectional study.
Ischemic stroke is a remarkable cause of death and disability worldwide. Post-stroke depression (PSD) is the most common psychiatric disturbance after stroke. Despite PSD being a potentially treatable condition, it still requires approaches to improve the early diagnosis. The present study aims to investigate the factors associated and correlated variables associated with PSD during hospitalization. A retrospective cross-sectional study was conducted in a specialized center of neurology in Santa Catarina, Brazil. 148 patients with acute ischemic stroke hospitalized between January 2020 and February 2021 were included. Sociodemographic, clinical and radiological variables were assessed during hospitalization. The Hospital Anxiety and Depression Scale (HADS) was applied, as well as the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Factors associated were investigated through binary logistic regression and continuous variables through correlation tests. The prevalence of PSD during hospitalization was 31.1%. Factors associated with PSD in the acute phase of the stroke were female sex (OR: 2.6; CI 95%: 1.3-5.4; p < 0.01) and post-stroke anxiety during hospitalization (OR: 4.9; CI 95%: 2.3-10.3; p < 0.01). The variables NIHSS, mRS, and stroke area were positively correlated with HADS - depression values. This research evidenced a high prevalence of PSD in the acute phase of stroke. Despite the study being conducted during the COVID-19 pandemic, the frequency is similar to the non-pandemic periods. The research provided clues to identify and timely treat patients at greater risk of developing PSD during hospitalization.


Absence of paradoxical pulse in patients with cardiac tamponade and atrial septal defects.
Five patients with atrial septal defect and proved cardiac tamponade had neither paradoxical pulse nor the inspiratory reduction of left ventricular internal dimension associated with this sign. It is assumed that equilibration of flow across the atrial septal defect prevented paradoxical pulse. Patients with a large atrial septal defect and tamponade do not manifest a paradoxical pulse.


LINC01225 promotes occurrence and metastasis of hepatocellular carcinoma in an epidermal growth factor receptor-dependent pathway.
The long noncoding RNAs (lncRNAs) have long been clarified to participate in hepatocellular carcinoma (HCC) as a biomarker. We carried out the present study in order to identify HCC-related lncRNAs and elucidate the functional roles in the development and progression of HCC. Our previous study has provided that LINC01225 may be an HCC-related gene. Here, we verified that LINC01225 was upregulated in HCC. Knockdown of LINC01225 resulted in inhibited cell proliferation and invasion with activated apoptosis and cell cycle arrest in vitro. Overexpression of LINC01225 in LINC01225 knockdown cells presented that attenuated cell proliferation and invasion were restored and enhanced. Subcutaneous and tail vein/intraperitoneal injection xenotransplantation model in vivo validated reduced tumor progression and metastasis. Investigation of mechanism found that LINC01225 could bind to epidermal growth factor receptor (EGFR) and increase the protein level of EGFR, and subsequently fine tune the EGFR/Ras/Raf-1/MEK/MAPK signaling pathway. Analysis with clinicopathological information suggested a high expression of LINC01225 is positively associated with poor prognosis. We also proved that LINC01225 was stably expressed in serum and can act as a novel biomarker in predicting the diagnosis of HCC. As a conclusion, LINC01225 plays a crucial role in HCC and can act as a biomarker for the diagnosis and prognosis of HCC.


Mucosal mast cells of the rat intestine: a re-evaluation of fixation and staining properties, with special reference to protein blocking and solubility of the granular glycosaminoglycan.
Mucosal mast cells of the gastrointestinal tract constitute a separate cell line within the mast cell system of the rat, differing in several respects from the classical connective tissue mast cells and, unlike the latter, requiring special fixation techniques for their demonstration. We have examined some histochemical properties of mucosal mast cells of the duodenum and compared them with connective tissue mast cells of the tongue or skin. The results indicate that the structural integrity of the granules of both types of mast cell is partly dependent on ionic linkages between glycosaminoglycan and protein. The so far unidentified glycosaminoglycan of mucosal mast cells appears to be more soluble than the heparin of connective tissue mast cells. The strongly fluorescent binding of Berberine to the granules of connective tissue mast cells and, depending on their content, of heparin is absent from mucosal mast cells, confirming previous findings which suggested that they contain a glycosaminoglycan with a lower degree of sulphation. Aldehyde fixation by routine procedures reversibly blocks the cationic dye binding of mucosal mast cell granules. The dye binding groups may be unmasked by trypsination or by long staining times of the order of several days. The results suggest that the blocking of staining by aldehydes is caused by a diffusion barrier of a protein nature. Mucosal and connective tissue mast cells thus differ with respect to the spatial arrangement of glycosaminoglycan and protein in their granules. As a result of the study a modified method for the demonstration of mucosal mast cells in tissue sections is described, based on normal formaldehyde fixation and staining in Toluidine Blue for a long time. It has some advantages over previous methods and preserves the structure of mucosal and connective tissue mast cells equally well.


Improved delivery of sinus irrigations after middle turbinate resection during endoscopic sinus surgery.
Improvement in topical delivery to nasal mucosa is a fundamental goal of endoscopic sinus surgery (ESS). This study compares the penetration of irrigation before and after middle turbinate resection (MTR) to assess the efficacy of topical delivery. ESS was performed on 4 cadaver heads, followed by MTR. Each head was irrigated with fluorescein-dyed water using a squeeze bottle both before and after MTR. Videos were recorded by rigid nasal endoscopy. Four blinded raters reviewed videos and scored the extent of staining (0 to 3) for each site. The mean score for the extent of staining of all anatomical sites before and after MTR was 1.30 and 1.92, respectively (p = 0.035). The mean score for extent of staining before and after MTR was 2.56 and 2.81 (p = 0.134) for the maxillary sinus, 1.66 and 2.25 (p = 0.022) for the ethmoid sinus, 1.03 and 1.94 (p = 0.263) for the sphenoid sinus, 0.16 and 0.94 (p = 0.055) for the frontal sinus, and 1.09 and 1.66 (p = 0.340) for the olfactory cleft, respectively. When evaluating interrater reliability, Cronbach's alpha was 0.92, which is acceptable. When evaluating intrarater reliability, the Fleiss kappa statistic for each rater was excellent or good. Overall, MTR results in significant improvement in the penetration of nasal irrigations in the cadaver model. Each individual sinus displays a trend toward improvement; however, only the ethmoid sinus displays a statistically significant improvement. Further in vivo studies are needed to elucidate the role of MTR.


The increasing role of phosphatidylethanolamine as a lipid receptor in the action of host defence peptides.
Host defence peptides (HDPs) are antimicrobial agents produced by organisms across the prokaryotic and eukaryotic kingdoms. Many prokaryotes produce HDPs, which utilise lipid and protein receptors in the membranes of bacterial competitors to facilitate their antibacterial action and thereby survive in their niche environment. As a major example, it is well established that cinnamycin and duramycins from Streptomyces have a high affinity for phosphatidylethanolamine (PE) and exhibit activity against other Gram-positive organisms, such as Bacillus. In contrast, although eukaryotic HDPs utilise membrane interactive mechanisms to facilitate their antimicrobial activity, the prevailing view has long been that these mechanisms do not involve membrane receptors. However, this view has been recently challenged by reports that a number of eukaryotic HDPs such as plant cyclotides also use PE as a receptor to promote their antimicrobial activities. Here, we review current understanding of the mechanisms that underpin the use of PE as a receptor in the antimicrobial and other biological actions of HDPs and describe medical and biotechnical uses of these peptides, which range from tumour imaging and detection to inclusion in topical microbicidal gels to prevent the sexual transmission of HIV.


Determination of the vaporization order of crude oils through the chemical analysis of crude oil residues burned on water.
To determine the vaporization order of (the components in) crude oils, the density, the viscosity and the chemical composition of a light and a heavy crude oil were studied as a function of the burning efficiency. An experimental series of small scale in-situ crude oil burns on water were conducted with the two crude oils. Chemical analyses of the burned residues showed that the components in crude oils vaporize in order of decreasing volatility and the depletion rate of components generally decreased with increasing molecular mass. Ultimately, this means that the burning efficiency of a crude oil burning on water can be related to fire dynamics principles, irrespective of its chemical and physical properties. The relative abundance of pyrogenic PAHs in the burned residues increased up to a maximum of 2600% for the light crude oil and 9100% for the heavy crude oil. Increased abundances of the pyrogenic PAHs were caused by the formation of the pyrogenic PAHs during the burning and not by an increase in concentration in the burned residues. Overall, the results provide relevant data for predicting the effectiveness of in-situ burning of crude oil as oil spill response method, both in terms of its burning efficiency and its environmental impact.


Effect of colloidal carriers on ascorbyl palmitate stability.
Active compounds can be protected against degradation by incorporation into colloidal carrier systems. The stabilizing effect of carrier systems for ascorbyl palmitate (AP) was investigated using microemulsions (ME), liposomes and solid lipid nanoparticles (SLN). Analysis of chemical stability by HPLC showed that AP is most resistant against oxidation in non-hydrogenated soybean lecithin liposomes, followed by SLN, w/o and o/w ME, and hydrogenated soybean lecithin liposomes. The molecular environment of the AP-like nitroxide probe (C(16)-Tempo) in colloidal carriers was characterized using electron paramagnetic resonance (EPR) spectroscopy. We have found that the nitroxide groups are located in environments with different polarity and mobility. The hydrophilic part of AP is the reactive moiety, and high stability is obtained in systems in which this part is exposed to a less polar environment. Additionally, the determined accessibility of nitroxide groups to reduction correlated well with the chemical stability of AP. It is more deeply immersed in the interface when entrapped in a liquid-state carrier than when applied in gel-state particles. Encapsulation of AP in SLN core leads to greater stability. We conclude that the location of the sensitive group of the drug-molecule in a carrier system is crucial for its stability.


Evaluation of elevated liver enzymes.
Liver enzymes, including aminotransferases and alkaline phosphatase, are some of the most commonly ordered blood tests in a physician's practice. These enzymes have been valuable in screening for liver disease, as well as in diagnosing and monitoring patients with acute and chronic hepatobiliary disorders. Patients with predominantly aminotransferase elevations are thought to have acute or chronic hepatitis from a variety of causes. In patients with predominantly alkaline phosphatase elevations, imaging evaluation is undertaken upfront to exclude large bile duct disorders and infiltrative/mass lesions. A liver biopsy may be reserved for patients for whom these less invasive investigations are unfruitful.


The effect of hemodialysis session on postural strategies in older end-stage renal disease patients.
Patients suffering from end-stage renal disease experience multiple disabilities, such as muscle wasting, weakness, higher postural sway, and fall rates compared with healthy population, which has a negative effect on physical functioning and autonomy. The vital treatment of hemodialysis is recognized to induce important post-hemodialysis fatigue, hypotension, cramps, and headache due to the rapid fluid redistribution, among others. Nevertheless, even the well-known negative effect of aforementioned consequences of hemodialysis treatment, its effect on physical function, especially postural balance, is unclear. Thus, this study hypothesized the adverse effect of hemodialysis treatment on postural sway in 12 end-stage renal disease patients (mean age 63.3 ± 11 years) through the analysis of center-of-pressure (COP) trajectories recorded before and immediately after hemodialysis session. Evident postural alterations were observed at post-hemodialysis balance assessment for COP position-based (Fs < 7.7, P < 0.02) and COP velocity-based variables (Fs > 2.33, P < 0.05), without changes in complexity of COP time series in anteroposterior and mediolateral directions. These results suggest that period after hemodialysis treatment is particularly unsafe, as evidenced by important disability in postural control, and highlight the importance of the medical support and falls-related prevention strategies of these older frail patients after hemodialysis treatment.


Differential scanning microcalorimetry study of the thermal denaturation of haemoglobin.
A study of thermal denaturation of human haemoglobin A0 (HbA0) and methaemoglobin (mHb) was carried out by differential scanning calorimetry. DSC haemoglobin profiles were scan rate dependent and only partly reversible. Thermal unfolding of protein was analysed with the use of both equilibrium thermodynamic and kinetic approaches. The fittings based on the simple equilibrium/dissociation model were good and much more satisfactory than those based on "fully-kinetic" models. However the presence of some kinetic distortion during the unfolding process should be noted due to the scan-rate effect on DSC transitions. The calculated first-order kinetic constant for mHb was higher by two orders than the one for HbA0 (stabilised form). The average activation energy for HbA0 was found to be 289 +/- 28 kJ M-1 while for mHb it was about 100 kj M-1 lower.


Modeling the complexity of dynamic, momentary interpersonal behavior: Applying the time-varying effect model to test predictions from interpersonal theory.
This paper demonstrates a recently-popularized quantitative method, the time-varying effect model (TVEM), in describing dynamic, momentary interpersonal processes implicated by Interpersonal Theory. We investigated moment-to-moment complementarity in affiliation and control behaviors (i.e., correspondence in affiliation and reciprocity in control between married dyad members) in a five-minute interaction (N=135), and how complementarity changed over time. Overall, results supported complementarity in affiliation and control. Moreover, effects were time-varying: Complementarity in affiliation increased over time and complementary in control changed over time in a cyclical manner. Dyadic adjustment moderated the strength in complementarity in control during specific timeframes. We discuss implications of these results and future directions. The findings support the utility of TVEM for studying dynamic and time-dependent interpersonal processes.


[Immunoenzyme method of determination of antithrombin III].
Immunoenzymatic assay is developed for estimation of antithrombin III (AT-III). Sensitivity of the assay was 7.8 ng of AT-III per 1 ml. The test system developed corresponded to the requirements for serological assays. Estimation of AT-III in blood plasma of healthy persons and in patients with various diseases showed that the assay may be recommended for clinical practice.


AMPK Ameliorates Tau Acetylation and Memory Impairment Through Sirt1.
Alzheimer's disease (AD) is the most common neurodegenerative disease, but its underlying mechanism is still unclear and the identities of drugs for AD also lack. Tau acetylation has become potentially important post-translational modification of tau. Levels of tau acetylation are significantly enhanced in AD patients and transgenic mouse models of AD, but the underlying mechanism and roles of tau hyperacetylation in AD onset maintain elusive. In the current study, we found that tau acetylation is obviously enhanced and the activities of AMP-activated protein kinase (AMPK) and sirtuin1 (Sirt1) are significantly decreased in APP/PS1 and streptozotocin (STZ) mice and high glucose (HG)-treated cells. Moreover, we demonstrated that activation of AMPK reduces the level of tau acetylation and ameliorates memory impairment, and its mechanism is associated with activation of Sirt1. Taken together, AMPK might be a crucial upstream molecular to regulate acetylation of tau and become a new target for AD therapy in the future.


Best practices for multi-ancestry, meta-analytic transcriptome-wide association studies: Lessons from the Global Biobank Meta-analysis Initiative.
The Global Biobank Meta-analysis Initiative (GBMI), through its diversity, provides a valuable opportunity to study population-wide and ancestry-specific genetic associations. However, with multiple ascertainment strategies and multi-ancestry study populations across biobanks, GBMI presents unique challenges in implementing statistical genetics methods. Transcriptome-wide association studies (TWASs) boost detection power for and provide biological context to genetic associations by integrating genetic variant-to-trait associations from genome-wide association studies (GWASs) with predictive models of gene expression. TWASs present unique challenges beyond GWASs, especially in a multi-biobank, meta-analytic setting. Here, we present the GBMI TWAS pipeline, outlining practical considerations for ancestry and tissue specificity, meta-analytic strategies, and open challenges at every step of the framework. We advise conducting ancestry-stratified TWASs using ancestry-specific expression models and meta-analyzing results using inverse-variance weighting, showing the least test statistic inflation. Our work provides a foundation for adding transcriptomic context to biobank-linked GWASs, allowing for ancestry-aware discovery to accelerate genomic medicine.


User Testing to Improve Retrieval and Comprehension of Information in Guidelines to Improve Medicines Safety.
The aim of the study was to investigate the effectiveness of user testing for improving healthcare professionals' retrieval and comprehension of information in medicines guidelines. The United Kingdom's Injectable Medicines Guide was selected as a case study. This gives guidance to nurses on preparing and administering intravenous medicines on hospital wards, in line with standard UK practice. Three rounds of user testing were completed with 10 hospital nurses per round, using the Injectable Medicines Guide for voriconazole and aminophylline. Participants used the guidelines to answer 17 questions related to the administration of these medicines. Answers were scored for "finding" and "understanding" the required information. Semistructured interviews explored participants' opinions of guideline content, design, and wording, with responses analyzed thematically. The guidelines were revised between rounds. In round 1, 8 of 17 questions were answered correctly by all participants. Participants had difficulty with dose, dilution, administration rate, and adverse effects questions. Revisions included new subsections and increased calculation support. In round 2, 14 of 17 questions were answered correctly by all participants. Difficulty persisted with dose and administration rate questions and further revisions made. In round 3, 15 of 17 questions were answered correctly by all participants. Across all rounds, participants considered appropriate subheadings and information order as important for fast location of information. Specific, detailed, and practical instructions were perceived as important to improve understandability and usefulness. Key information in medicines guidelines may not be found and/or understood by healthcare professionals. User testing increased information retrieval and comprehension and could have an important role in improving the safety of medicines use.


How cardinal are cardinal symptoms in pediatric bipolar disorder? An examination of clinical correlates.
The main goal of this study was to test whether the hypothesized cardinal symptom of euphoria results in differences in clinical correlates in bipolar youth ascertained with no a priori assumptions about cardinal symptoms. Subjects (n = 86) satisfying DSM-IV criteria for bipolar disorder with and without the proposed cardinal symptom of euphoria were compared in their bipolar symptom pattern, functioning and patterns of comorbidity. Among Criterion A (abnormal mood), we found that severe irritability was the predominant abnormal mood rather than euphoria (94% vs. 51%). We also found that among Criterion B items, grandiosity was not uniquely overrepresented in youth with mania, nor did the rate of grandiosity differ whether irritability or irritability and euphoria were the Criterion A mood symptom. Neither symptom profile, patterns of comorbidity nor measures of functioning differed related to the presence or absence of euphoria. These findings challenge the notion that euphoria represents a cardinal symptom of mania in children. Instead they support the clinical relevance of severe irritability as the most common presentation of mania in the young. They also support the use of unmodified DSM-IV criteria in establishing the diagnosis of mania in pediatric populations.


AC-DC electropenetrography: fundamentals, controversies, and perspectives for arthropod pest management.
Studying the intimate association of arthropods with their physical substrate is both important and challenging. It is important because substrate is a key determinant for organism fitness; challenging because the intricacies of this association are dynamic, and difficult to record and resolve. The advent of electropenetrography (EPG) and subsequent developments allowed researchers to overcome this challenge. Nonetheless, EPG research has been historically restricted to piercing-sucking hemipteran plant pests. Recently, its potential use has been greatly broadened for additional pests with instrument advances. Thus, blood-feeding arthropods and chewing feeders, as well as non-feeding behaviors like oviposition by both pests and parasitoids, are novel new targets for EPG research, with critical consequences for integrated pest management. EPG can explain mechanisms of crop damage, plant or animal pathogen transmission, and the effects of insecticides, antifeedants, repellents, or transgenic plants and animals, on specific behaviors of damage or transmission. This review broadly covers the principles and development of EPG technology, emphasizing controversies and challenges remaining with suggested research to overcome them. In addition, it summarizes 60+ years of basic and applied EPG research, and previews future directions for pest management. The goal is to stimulate new applications for this unique enabling technology. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.


Cognitive deficits after general anaesthesia in animal models: a scoping review.
It remains controversial whether general anaesthetic drugs contribute to perioperative neurocognitive disorders in adult patients. Preclinical studies have generated conflicting results, likely because of differing animal models, study protocols, and measured outcomes. This scoping review of preclinical studies addressed the question: 'Do general anaesthetic drugs cause cognitive deficits in adult animals that persist after the drugs have been eliminated from the brain?' Reports of preclinical studies in the MEDLINE database published from 1953 to 2021 were examined. A structured review process was used to assess original studies of cognitive behaviours, which were measured after treatment (≥24 h) with commonly used general anaesthetic drugs in adult animals. The initial search yielded 380 articles, of which 106 were fully analysed. The most frequently studied animal model was male (81%; n=86/106) rodents (n=106/106) between 2-3 months or 18-20 months of age. Volatile anaesthetic drugs were more frequently studied than injected drugs, and common outcomes were memory behaviours assessed using the Morris water maze and fear conditioning assays. Cognitive deficits were detected in 77% of studies (n=82/106) and were more frequent in studies of older animals (89%), after inhaled anaesthetics, and longer drug treatments. Limitations of the studies included a lack of physiological monitoring, mortality data, and risk of bias attributable to the absence of randomisation and blinding. Most studies reported cognitive deficits after general anaesthesia, with age, use of volatile anaesthetic drugs, and duration of anaesthesia as risk factors. Recommendations to improve study design and guide future research are presented.


Teaching psychiatry to medical students on a consultation service.
Medical students experience psychiatric consultation as part of their undergraduate psychiatric clerkship experience. This allows further identification of the medical student with the psychiatrist in management of psychiatric problems in patient who are primarily non-psychiatric. Reaction has tended to be favourable from the medical students without a great loss of speed or efficiency in terms of the service committment.


Purification and properties of S-adenosyl-L-methionine: caffeic acid O-methyltransferase from leaves of spinach beet (Beta vulgaris L).
1. An enzyme catalysing the methylation of caffeic acid to ferulic acid, using S-adenosyl-L-methionine as methyl donor, has been extracted from leaves of spinach beet and purified 75-fold to obtain a stable preparation. 2. The enzyme showed optimum activity at pH 6.5, and did not require the addition of Mg2+ for maximum activity. 3. It was most active with caffeic acid, but showed some activity with catechol, protocatechuic acid and 3,4-dihydroxybenzaldehyde. The Km for caffeic acid was 68 muM. 4. 4. The Km for S-adenosyl-L-methionine was 12.5 muM. S-Adenosyl-L-homocystein (Ki = 4.4 muM) was a competitive inhibitor of S-adenosyl-L-methionine. 5. The synthesis of S-adenosyl-L-homocysteine from adenosine and L-homocysteine and its consequent effect on caffeic acid methylation were demonstrated with a partially-purified preparation from spinach-beet leaves, which possessed both S-adenosyl-L-homocysteine hydrolase (EC 22.214.171.124) and adenosine nucleosidase (EC 22.214.171.124) activities. This preparation was also able to catalyse the rapid breakdown of S-adenosyl-L-homocysteine to adenosine and adenine; the possible significance of this reaction in relieving the inhibition of caffeic acid methylation by S-adenosyl-L-homocystein is discussed.


Childhood optic neuritis: the pediatric neurologist's perspective.
Optic neuritis in children may be an isolated, usually postinfectious event, or the symptom of a more widespread disorder. To investigate the etiological spectrum of optic neuritis in children in association with diagnostic findings and follow-up results. We retrospectively examined the records of 31 children aged 4-15 (mean 9.7+/-2.9) years in whom isolated optic neuritis was the presenting neurological symptom. Monophasic bilateral optic neuritis was the most common presentation (45%), followed by the unilateral (32%) and recurrent (22%) forms. Initial cranial MRI was abnormal in 12/31 patients. During a mean follow-up of 2.2 years (6 months-15 years), 6/14 bilateral cases, 9/10 unilateral and 5/7 recurrent cases were diagnosed with various disorders including total eight with MS. The MS group tended to start with unilateral optic neuritis, was older (mean 11.6+/-1.5 vs. 8.8+/-2.9 years), and included more girls than the other groups. Optic neuritis in children is frequently part of a systemic or neurological disorder even in the presence of normal cranial imaging. These patients should be evaluated and followed-up in pediatric neurology clinics.


Manganese intoxication: the cause of an inexplicable epileptic syndrome in a 3 year old child.
Excess manganese (Mn) can cause several neurotoxic effects, however only a few studies have reported epileptic syndromes related to manganese intoxication. We describe an epileptic syndrome due to manganese intoxication in a 3 year old male child. His blood manganese was elevated, but no other abnormal values or toxic substances were found in blood or urine. The electroencephalogram (EEG) showed a picture of progressive encephalopathy, while brain magnetic resonance was normal. The patient's conditions rapidly worsened to epileptic status despite the use of antiepileptic drugs. Chelating treatment with CaNa(2)EDTA was initiated to remove excess manganese and promptly succeeded in reverting epileptic symptoms. Concurrently, manganese blood levels and electroencephalogram progressively normalized. Thereafter it has been possible to discontinue antiepileptic treatment, and the patient remains in excellent conditions without any treatment.


Barium- or quinine-induced depolarization activates K+, Na+ and cationic conductances in frog proximal tubular cells.
1. Frog proximal tubular cells were fused into giant cells. We measured membrane potential (Vm), its changes (delta Vm), and current-induced voltage changes (delta psi) in single cells, during control and experimental states. Each cell served as its own control. 2. In the presence of a physiological Ringer solution, the transference number for potassium (tK) was 0.50. Barium (3 mM) reduced membrane conductance (Gm) by 50%; low-Cl- solutions and low-Na+ solutions also diminished Gm, by 52 and 30%, respectively. The association of barium and low-NaCl solutions decreased Gm to approximately 38% of control, indicating that the impermeant substitute of a physiological ion may interact with other pathways; alternatively, blockade of steady-state conductances may activate physiologically silent processes. 3. In an attempt to enhance the contribution of the partial K+ conductance (GK) to Gm, fused cells were exposed to low-Cl- solutions, containing in addition 0.1 mM-methazolamide, to inhibit the rheogenic Na(+)-HCO3-symport, and 1 microM-amiloride, to block Na+ conductance (GNa). tK went up to 0.83. 4. The high tK preparation was challenged with barium (3 mM) or quinine (Quin, 1 mM). These blockers produced large depolarizations (approximately 60 mV), however, although Gm decreased along early- and mid-depolarization, Gm plateaued and eventually it increased with larger and larger depolarization. 5. Depolarization-associated increase in Gm reflects activation of other conductances. These are Na+, cationic, and K+ conductance(s) poorly sensitive to quinine or barium. In the presence of Ba(2+)- or Quin-induced depolarization, injection of depolarizing current produces delayed increase in conductance. 6. Depolarization-induced activation of cationic conductance (Gcat) and GNa results in enlargement of the K+ electrochemical potential difference, to about 70 mV; this difference allows recycling of K+ ions outwards, since a GK is still detected and may contribute up to 38% of the total conductance.


Immunolocalization of prealbumin as a marker for carcinoid tumours.
Using a PAP immunoperoxidase technique, we have demonstrated the plasma protein prealbumin in 92 (87 per cent) out of a series of 106 carcinoid tumours from various sites. The frequency of detection was greater than with the conventional stains; 83 (78 per cent) of the cases were positive for one or more of these stains. The Grimelius technique was by far the most effective of the conventional stains; it was positive in 81 (76 per cent) cases. We were unable to detect prealbumin in a variety of carcinomas. Although prealbumin identification did not appear to have any advantage over the routine stains in midgut-derived carcinoids, it was much more effective in the diagnosis of bronchial (foregut) and rectal (hindgut) carcinoids. We believe that prealbumin staining offers a cheap, reliable and valuable method for the detection of carcinoid tumours in routine histopathology.


Turning the tide on obesity?
Genetics, ultraprocessed foods, portion distortion, sweetened beverages, screen time, food addiction, intestinal microbiota, diet culture, weight stigma, food insecurity-all have been implicated in the "obesity epidemic." More than a billion people worldwide have obesity, and many more are overweight. With the emergence of new, highly effective weight-loss drugs, might the "fat decades" become a closed chapter in the history of public health?


Metabolomics study of renal fibrosis and intervention effects of total aglycone extracts of Scutellaria baicalensis in unilateral ureteral obstruction rats.
Scutellariae Radix (Scutellaria baicalensis Georgi) is a well-known Traditional Chinese Medicine (TCM) which mainly contains flavonoids. Our previous studies have demonstrated that total aglycone extracts of Scutellaria baicalensis (TAES) can improve kidney disease in rats. To investigate the renal fibrosis (RF) pathogenesis and TAES treatment mechanism in unilateral ureteral obstruction (UUO) rats, using a metabolomics approach based on gas chromatography-mass spectrometry (GC/MS). Rats with RF were divided into 6 groups with rats subjected to sham operation as normal control. The effects of TAES on some RF closely related parameters in UUO rats were investigated. A metabolomics method, based on GC/MS, was developed to monitor metabolic alterations in urine. Multivariate data analysis was utilized to identify biomarkers potentially associated with RF and the anti-RF activity of TAES. Ontology-based enrichment analysis by BiNChE and pathway analysis by MetPA aid in the interpretation of difference metabolites. After 10 days of treatment, the parameters of renal function begin returning to normal, and the abnormal high expressions of genes associated with extracellular matrix (ECM) were relived. In the metabolomics study, metabolic perturbations induced by UUO were reversed after treatment and TAES showed a dose-dependent therapy effect on RF, meanwhile, 18 potential biomarkers associated with RF were identified. Enrichment analysis of metabolites shows an over representation of mostly alkane-alpha, omega-diamine and alpha, omega-dicarboxylic acid, and these biomarkers are primarily involved in Glycine, serine and threonine metabolism, Retinol metabolism, Arginine and proline metabolism and Fructose and mannose metabolism. Our findings indicate that TAES have positive effects on UUO-induced RF in rats, meanwhile, metabolomics method coupled with metabolites enrichment analysis is a useful tool for revealing the pathogenesis of diseases and action mechanism of TCM on the whole body.


Repetitive peripheral magnetic stimulation to reduce pain or improve sensorimotor impairments: A literature review on parameters of application and afferents recruitment.
Repetitive peripheral magnetic stimulation (rPMS over spinal root, nerve or muscle belly) is a promising technology in physiopathology research. As compared to electrical stimulation, rPMS is deemed to activate deep conductive structures and produce strong muscle contractions and massive proprioceptive afferents with minimal cutaneous recruitment. RPMS may thus act differently on neural plasticity involved in pain reduction and motor recovery in musculoskeletal or neurological conditions. However, literature is very scant and still controversial concerning afferents recruited by rPMS, thus no consensus is reached yet for its clinical use. This review dealt with stimulation parameters reported in any scientific research that applied rPMS as an intervention to improve somatosensory or motor disorders with a view of proposing recommendations for future applications. Also, controversy on afferents recruitment was discussed. The literature search resulted in 24 studies. Literature is scant on the topic but our review presents the rationale and the experimental data that may underlie the selection of parameters in future studies using rPMS as an intervention. Although controversy remains, the review presents that the specific recruitment of sensory afferents by magnetic stimulation may offer advantages and disadvantages depending on the pathology. The review proposed recommendations to improve rPMS application in clinical research. However, the development of guidelines still requires methodological and clinical studies enrolling larger samples and with randomized sham-controlled designs.


Body mass index and treatment outcomes following neoadjuvant therapy in women aged 45 y or younger: Evidence from a historic cohort.
Large and consistent evidence supports the role of body mass index (BMI) as a prognostic and predictive indicator in breast cancer. However, there is paucity of data specifically referred to women diagnosed at a young age across the different disease settings. We investigated the impact of BMI on treatment outcomes in 86 breast cancer patients aged 45 y or less treated with neoadjuvant chemotherapy (CT) followed by surgery. Pathologic complete response (pCR) was defined as the eradication of cancer from both breast and lymph nodes. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier product-limit method. Curves were compared by long rank test for significance. Potential predictors of survival were tested in Cox models. We observed a pCR in 19 patients (22%). Lower values of BMI were more commonly associated with pCR (p = 0.05). Results from univariate, but not multivariate, models were somewhat supportive of higher pCR rates in leaner women (p = 0.06). None of the variables impacted DFS. OS was longer in leaner patients (medians and 95%CI: 74.6 months, 66.2-82.9 and 58.5 months, 49.6-67.4, p = 0.009). Longer OS was also related to lower T-stage, adjuvant radiotherapy (RT), and non triple negative (TN) subtype (p = 0.046, p = 0.024, and p = 0.015, respectively). Cox models confirmed the protective role of lower BMI (Hazard Ratios: 0.30, 95%CI: 0.12-0.71, p = 0.007), non TN subtype and adjuvant RT (p = 0.008 and p = 0.024). In young breast cancer patients treated with neoadjuvant CT followed by surgery, lower values of BMI are associated with longer OS. Our data also showed longer OS in association with a non TN molecular subtype and adjuvant RT. The modifiable nature of BMI and aggressive biologic behavior of the disease diagnosed at a young age encourage further studies to corroborate our findings.


Hyperprolactinaemia and infertility following cranial irradiation for brain tumours: successful treatment with bromocriptine.
Two young women developed oligomenorrhoea and galactorrhoea 4 and 7 years after whole brain irradiation for brain tumours. Both had mild hyperprolactinaemia due to irradiation-induced hypothalamic damage. In both patients, oral bromocriptine normalized prolactin levels and menstruation resumed. One patient then had a successful pregnancy.


Cerebral ischemia induced apoptosis and necrosis in normal and diabetic rats.
Stroke is the third leading cause of death and disability, and the risk for ischemic stroke is greater in diabetics. Previous studies have demonstrated both structural and functional nervous system changes in diabetes, and these changes may be enhanced by apoptosis. In the present study, we evaluated several indexes of both necrosis and apoptosis in the CNS of normals and two different models of diabetes (insulinopenic and insulin-resistant). Studies were conducted following middle cerebral artery occlusion (MCAO) with or without reperfusion. The sensory motor cortex (layer-5 and -6) and the CA1 and CA3 sectors of the hippocampus were analyzed following MCAO. We observed that both insulinopenic and insulin-resistant diabetic rats have increased basal level of apoptosis that is uniformly and bilaterally distributed as indicated by both caspase-3 activity and TUNEL staining. Twenty-four hours after MCAO, apoptosis was further increased in both diabetic models. Reperfusion after a 2 h MCAO compared to 24 h MCAO was associated with a decrease in TUNEL staining and caspase-3 activity in the control animal but exacerbated apoptosis, especially in the hippocampus of insulin-resistant diabetic rats. MCAO-induced lesion volumes were greater in insulinopenic rats compared to insulin-resistant and control rats. We conclude that both insulinopenic and insulin-resistant diabetic animals have increased apoptosis in the CNS in response to MCAO, and restoration of blood flow especially in the insulinopenic diabetic animals paradoxically exacerbates this process. Furthermore, restoration of blood flow did not decrease lesion volume in insulinopenic diabetic animals.


Intradural spinal cysts.
18 cases of benign intradural spinal cyst (9 arachnoidal, 2 neuroepithelial, 7 endodermal) are reported and compared with 94 cases (67 arachnoidal, 7 neuroepithelial, 20 endodermal) obtained from the literature. Arachnoidal intradural cysts (AIC) have no sex preference, occur at around the fourth-fifth decades of life and have characteristic intermittent root symptoms. They prefer the thoracic level and the posterior position. (Myelography images the cystic cavity (diverticular form). Surgical removal is usually easy. Neuroepithelial intradural cysts (NIC) are rare, have a 2:1 predilection for females and occur after the fourth decade. They have a serious clinical course similar to intramedullary or extramedullary tumours. They prefer the conus-cauda and the anterolateral positions. They often give rise to manometric block and to albuminocytological dissociation. There may be substantial adhesions to the cord and roots and the intramedullary variety presents no clear plane of cleavage. Endodermal intradural cysts (EIC) have a 2:1 predilection for males and prefer the second and third decades. They may have an intermittent or serious course with signs of root and cord impairment. They prefer the cervical segment (in the anterior position) and the conus-cauda (in the posterior position). As a rule they present manometric block and albuminocytological dissociation. Their frequent tough adhesions to the roots and cord demand special care during their removal.


Ectopic secretion of GHRH by a pancreatic neuroendocrine tumor associated with an empty sella.
Acromegaly is usually the result of a pituitary growth hormone cell-adenoma or is more rarely due to ectopic secretion of growth hormone releasing hormone (GHRH).We report the case of a 60-year-old woman with acromegaly due to a GH-RH-secreting pancreatic tumor. Laboratory evaluation confirmed the diagnosis of acromegaly. Magnetic resonance imaging revealed a partial empty sella with no signs of adenoma. Ultrasound sonography performed for abdominal pains showed a calcified large heterogeneous infrahepatic mass. Computed tomography scan discovered a heterogeneous pancreatic head mass with a diameter of 10cm. Measurement of fasting plasma GHRH was performed showing a high concentration of 604ng/L (normal 10-60). We therefore concluded that the acromegaly was caused by ectopic overproduction of GHRH likely due to the pancreatic tumor. The patient underwent a cephalic duodenopancreatectomy. Histology revealed a well-circumscribed tumor with organoid architecture. Immunohistochemistry demonstrated diffuse positivity for chromogranin A, neuronal specific enolase and synaptophysin and negative immunoreactivity for prolactin, GH and serotonin. These features were concordant with a well-differentiated neuroendocrine tumor of the pancreas. Surgical resection of this pancreatic tumor was followed by significant amelioration of acromegalic signs and normalization of GHRH and GH levels.


[Bariatric surgery in a patient with adipositas permagna and uncontrolled insulin resistance].
A 58-year-old patient had a 21 years history of diabetes mellitus and multiple diabetic complications. In addition he suffered from severe obesity with a body mass index of 42.7 kg/m² and a waist circumference of 141 cm. After all treatment options according to the national guidelines had failed the patient was admitted to a diabetes clinic. All approaches on the metabolic ward to control insulin resistance failed as well and finally blood glucose levels could only be stabilized with the aid of continous subcutaneous insulin infusion with more than 500 units per day. The patient's quality of life and the options for physical activity were extremely limited. Thus, the indication of bariatric surgery was discussed with the interdisciplinary team of specialists and with the patient. After informed consent a Roux-Y gastric bypass was established with the aid of minimal invasive surgery. Already two weeks after the operation insulin demand had decreased to 100 units per day and metabolic control and the treatment could be further optimized. Three months later the body mass index was reduced to 34.3 kg/m². The treatment improved the patient's quality of life, optimized metabolic control and resulted last but not least in lower costs for the diabetes treatment. Bariatric surgery is an additional option in the treatment of obesity and insulin resistance. The collaboration between diabetologists and bariatric surgeons is a prerequisite for the successful selection of patients and for longterm control after surgery.


A novel HEXB mutation and its structural effects in juvenile Sandhoff disease.
Mutations in HEXB, encoding the beta-subunit common to hexosaminidases A and B, cause the neurodegenerative condition, Sandhoff disease. A homozygous missense HEXB mutation (p. D459A) was discovered in six patients with a rare juvenile variant: we show that this disrupts a salt bridge between aspartate D459 and arginine 505 at the subunit interface; R505 mutations are reported in late-onset Sandhoff disease. Identification of D459A contributes to diagnosis and molecular understanding of attenuated Sandhoff disease variants.


Effect of shear velocity and feed concentration on the treatment of food waste in an anaerobic dynamic membrane Bioreactor: Performance Monitoring and microbial community analysis.
The formation of the dynamic membrane (DM) in an anaerobic dynamic membrane bioreactor (AnDMBR) treating food waste was, previously, found to be beneficial to the stable performance of an anaerobic digestion system. This study examines the effect of shear velocity and feed concentration on the performance and microbial community of an AnDMBR treating food waste. The shear velocity was varied from 0.04 to 1.74 m/h, using three different feed concentrations (50, 80, and 100 g-COD/L). The highest average methane production rate of 2.6 L-CH4/L/d was achieved at a feed concentration and shear velocity of 100-g COD/L and 0.34 m/h, respectively. Increasing shear velocity, within certain limits, is beneficial to AnDMBR systems, promoting better mixing, substrate-biomass interactions, and DM layer formation. Methanosarcina flavescens proliferated (69%) at high shear velocities when acetic acid was the major volatile fatty acid. The abundance ratio between Bacteroidetes and Firmicutes showed a linear relationship to methanogenic performance.


From Abandonment to Hospitalisation: Evolution of Hospital Care in Rural Spain (1939-1975).
The aim of this article is to explain the situation of the Spanish hospital system during the twentieth century and to analyse the reasons why the difficulties that a significant part of the Spanish population, resident in rural areas, had to access hospital services during the Franco dictatorship were perpetuated. The first section uses a conceptual perspective to discuss the repercussions that the new medical significance of the hospital had for the notion of 'rural hospital'. The second section examines the projects for hospital modernisation that appeared before the Spanish Civil War (1936-39) and highlights what impeded the consolidation of these pioneering experiences in the country. The following section analyses the hospital situation in Spain's rural world as well as the profound changes that occurred during the last decades of the dictatorship, just on the threshold of the health reform that was finally implemented in the democratic period.


High treatment burden in adults with cystic fibrosis: challenges to disease self-management.
More aggressive management of cystic fibrosis (CF), along with the use of new therapies, has led to increasing survival. Thus, the recommended daily treatment regimens for most CF adults are complex and time consuming. In the Project on Adult Care in CF (PAC-CF), an ongoing longitudinal study of CF adults, we assessed self-reported daily treatment activities and perceived treatment burden as measured by the CF Questionnaire-Revised (CFQ-R), a disease-specific quality of life measure. Among the 204 respondents, the median number of daily therapies reported was 7 (IQR 5-9) and the mean reported time spent on treatment activities was 108 minutes per day (SD 58 min). Respondents reported a median of 3 inhaled and 3 oral therapies on the day prior to the survey. Only 49% reported performing airway clearance (ACT) on that day. There were no differences in the number of medications or the time to complete therapies based on gender, age or FEV1. The mean CFQ-R treatment burden domain score was 52.3 (SD 22.1), with no significant differences in the treatment burden based on age or FEV1. In a multivariable model controlling for age, gender, and FEV1, using 2 or more nebulized medications and performing ACT for >or=30 min were significantly associated with increased treatment burden. The level of daily treatment activity is high for CF adults regardless of age or disease severity. Increasing number of nebulized therapies and increased ACT time, but not gender, age, or pulmonary function, are associated with higher perceived treatment burden. Efforts to assess the effects of high treatment burden on outcomes such as quality of life are warranted.


Functional interplay between glutathione and hydrogen sulfide in regulation of thiol cascade during arsenate tolerance of common bean (Phaseolus vulgaris L.) genotypes.
Changes in expressions of up- and downstream thiol cascade were studied in leaves of Phaseolus vulgaris L. cv. VL-63 and its mutant, pvsod1 (deficient in superoxide dismutase activity) under 50 μM sodium arsenate (As), As + L-buthionine-sulfoximine (BSO) and As + BSO + Sodium hydrosulfide (NaHS)-treatments for 10 days. Main objective was to investigate the functional relationship between hydrogen sulfide (H2S) and glutathione (GSH) in regulation of sulfate transporters and cysteine metabolisms as up-stream thiol components and GSH, phytochelatins (PCs) and antioxidant defense response as downstream cascade under As-exposure. As treatment alone initiated coordinated inductions of sulfate transport, biosynthesis of cysteine, GSH, and PCs, and GSH-mediated antioxidant defense in the pvsod1 mutant. At As + BSO, GSH synthesis was blocked, resulting in significantly low GSH redox pool and steep decline in GSH-dependent antioxidant capacity of both the genotypes. However, unlike VL-63, cysteine-degradation pathway was induced in pvsod1 mutant, resulting in significant accumulation of endogenous H2S. The H2S-surge in the pvsod1 mutant stimulated ascorbate-dependent antioxidant defense and catalases and regulated O-acetylserine (thiol)lyase activity, preventing overaccumulation of H2O2 and free cysteine, respectively. No As-induced oxidative stress symptom was observed in the mutant. This trend was maintained at As + BSO + NaHS treatment, also. In contrast, failure to induce entire cascade from sulfate transport to downstream antioxidant defense led to onset of As-induced oxidative damage in VL-63 plant. Results revealed dual roles of H2S as (a) stimulator of GSH-independent antioxidant defense and (b) regulator of cysteine homeostasis through its metabolic diversion during As-exposure and blockage of GSH biosynthesis.


Cross-sectional study on relationships between physical function and psychological readiness to return to sport after anterior cruciate ligament reconstruction.
Information about specific factors of physical function that contribute to psychological readiness is needed to plan rehabilitation for a return to sports. The purpose of this study was to identify specific physical functions related to the psychological readiness of patients aiming to return to sports 6 months after reconstruction. We hypothesized that the knee strength is a factor related to the Anterior Cruciate Ligament-Return to Sport after Injury scale (ACL-RSI) cutoff score for a return to sports. This was a cross-sectional study. Fifty-four patients who had undergone primary reconstruction using hamstring tendon participated in this study. Psychological readiness was measured using the ACL-RSI in patients at 6 months after reconstruction. To identify specific physical functions related to the ACL-RSI score, participants were divided into groups with ACL-RSI scores of ≥ 60 or < 60. Non-paired t-tests or the Mann-Whitney test were performed to analyze group differences in objective variables in physical function: (1) knee strength in both legs; (2) leg anterior reach distance on both sides; and (3) single-leg hop (SLH) distances in three directions for both legs. Significant differences between groups were identified in knee flexion strength (60°/s) for the uninvolved limb, hamstring-to-quadriceps ratio (60°/s) for the uninvolved limb, knee flexion strength (180°/s) for the involved limb, limb symmetry index (LSI) of leg anterior reach distance, the ratio of the distance to the height of the patient and LSI of SLH distances in lateral and medial directions. This study revealed that at 6 months after reconstruction, increased knee flexion strength (ratio of peak torque measured to body mass of the patient), hamstring-to-quadriceps ratio, leg anterior reach distance LSI, and lateral and medial SLH appear important to exceed the ACL-RSI cutoff for a return to sports. The present results may be useful for planning post-operative rehabilitation for long-term return to sports after reconstruction.


The effects of training group exercise class instructors to adopt a motivationally adaptive communication style.
Drawing from self-determination theory (Deci & Ryan, 2002), we developed and tested an intervention to train fitness instructors to adopt a motivationally adaptive communication style when interacting with exercisers. This was a parallel group, two-arm quasi-experimental design. Participants in the intervention arm were 29 indoor cycling instructors (n = 10 for the control arm) and 246 class members (n = 75 for the control arm). The intervention consisted of face-to-face workshops, education/information video clips, group discussions and activities, brainstorming, individual planning, and practical tasks in the cycling studio. Instructors and exercisers responded to validated questionnaires about instructors' use of motivational strategies and other motivation-related variables before the first workshop and at the end of the third and final workshop (4 months later). Time × arm interactions revealed no significant effects, possibly due to the large attrition of instructors and exercisers in the control arm. Within-group analyses in the intervention arm showed that exercisers' perceptions of instructor motivationally adaptive strategies, psychological need satisfaction, and intentions to remain in the class increased over time. Similarly, instructors in the intervention arm reported being less controlling and experiencing more need satisfaction over time. These results offer initial promising evidence for the positive impact of the training.


Preparation, high-performance liquid chromatographic separation and characterization of hexacarboxylic porphyrinogens.
A simple method for the preparation and reversed-phase high-performance liquid chromatographic separation of hexacarboxylic porphyrinogen isomers is described. Uroporphyrin I or III was partially decarboxylated in 0.5 M hydrochloric acid at 150 degrees C. Unreacted uroporphyrin and the hepta-, hexa- and pentacarboxylic porphyrins formed were esterified and then group-separated by thin-layer chromatography. After hydrolysis, the porphyrins were reduced to the corresponding porphyrinogens with 3% (w/w) sodium amalgam. The hexacarboxylic porphyrinogens were separated on an ODS-Hypersil column by elution with acetonitrile-methanol-1 M ammonium acetate, pH 5.16 (8:12:80, v/v/v) as mobile phase. Isomers were identified by high-performance liquid chromatography of the characteristic mixture of two pentacarboxylic porphyrins formed after partial decarboxylation of individual isomers. Except for the two type I isomers, resolution of the hexacarboxylic porphyrinogens was superior to that of the corresponding porphyrins.


Mobile web-based self-management program for breast cancer patients with chemotherapy-induced amenorrhoea: A quasi-experimental study.
The aim of this study was to examine the effects of a mobile web-based self-management program on menopausal symptoms, self-efficacy and quality of life in breast cancer patients with chemotherapy-induced amenorrhoea. A quasi-experimental pretest-posttest design with repeated measures. The study was carried out at a university medical centre between October 2017 and September 2018. The intervention group received a 12-week mobile web-based self-management program including education and coaching/support. Multiple instruments were used to measure menopausal symptoms, self-efficacy, and quality of life at pre-test, after the intervention (post-test), and 3 months post-intervention (follow-up test). Repeated measure ANOVA was used to analyse the data. In the intervention group, menopausal symptoms were significantly improved compared to the control group at the follow-up test. In the follow-up test, the intervention group's self-efficacy and quality of life were significantly improved, whereas that of the control group was decreased.


Isorhythmic Dissociation--a "physiological" arrhythmia.
The behavior of the sino-atrial mechanism in isorhythmic dissociation (IRD) was studied in 21 patients, nine with spontaneous IRD and 12 with artificially pacemaker-induced IRD following electrode placement for heart block. Successive P-P, R-R and P-R intervals and blood pressure (BP) fluctuations were determined and graphically interrelated at control and during IRD. Several features were observed: a. IRD was present only when the independent ventricular rate was close to the atrial; b. P rate oscillations closely followed the P-R interval-dependent BP fluctuations (mean difference 30 mmHg) during IRD. In cardiogenic shock and in severe hypertension IRD could not be achieved easily; c. While during complete dissociation or during 1:1 A-V conduction the sinus rate was remarkably constant (2-4 beats/min variations), it showed marked oscillations (differences of 6-19, mean 13, beats/min) during IRD. All the data and calculations support the theory that in most instances of IRD, the arrhythmia is sustained by the normal physiologically active baroreceptor reflex arc.


Association between the mesenchymal compartment of uterovaginal organogenesis and local tumour spread in stage IB-IIB cervical carcinoma: a prospective study.
Macroscopic, microscopic, and occult local tumour spread might be restricted to a permissive territory related to the morphogenesis of the tissue or organ from which the tumour originates. We aimed to define such a morphogenetic unit in Müllerian development, and to assess the role of total mesometrial resection in the treatment of patients with stage IB-IIB cervical carcinoma. We analysed uterovaginal development in serial sections of female human embryos and fetuses, and defined the distal Müllerian morphogenetic unit from the Müllerian mesenchyme. We assessed prospectively the histopathological and clinical findings from patients who underwent total mesometrial resection-modified surgery for stage IB-IIB cervical carcinoma that aims to remove the uterus, proximal vagina, and extracervical mesenchyme within the borders of the distal Müllerian morphogenetic unit. The spatial extension of the Müllerian mesenchyme, its vascularisation, and its innervation during early uterovaginal organogenesis determine a tissue territory that can be followed during fetal development and identified in women as a morphogenetic unit. 105 of 106 patients who had total mesometrial resection, 63 of whom were classed as high risk, had microscopically tumour-free resection margins (ie, R0). 48 (96%) of 50 patients had pelvic recurrence-free survival at 3 years (95% CI 92-100) without adjuvant radiotherapy. Radical en-bloc resection of a topographically defined anatomical territory derived from common precursor tissue leads to local tumour control, preservation of autonomic nerves, and a reduced need for adjuvant radiotherapy.


Effect of prostaglandin E2 on serum iron after acute and chronic blood loss.
The effect of prostaglandin E2 on serum iron of New Zealand rabbits subjected to acute and chronic blood loss is demonstrated. The results showed that acute blood loss was followed by significant elevation of serum iron when sera were tested on day three after the bleeding. With subcutaneous injection of 40 micrograms/kg body weight of prostaglandin E2 for each 12 h of the experiment, acute blood loss was followed by a significant reduction in serum iron within the same period. Similar results were obtained after chronic blood loss when subcutaneous injection of 20 micrograms/kg body weight of prostaglandin E2 was used for each 12 h of the experiment. It could be concluded that the prostaglandin E2 causes marked lowering of serum iron following blood loss.


Interleukin-3 supports growth of mouse pre-B-cell clones in vitro.
Study of the differentiation of immunoglobulin-producing B lymphocytes has been hampered by the inability to maintain homogeneous populations of precursor cells in vitro. We describe here that interleukin-3 supports the growth of freshly isolated fetal liver pre-B cells and the long-term culture of interleukin-3 dependent pre-B-cell clones that can be induced to mature into antibody secreting cells in vitro.


Parent-reported symptoms may not be adequate to define asthma control in children.
Asthma guidelines have suggested that treatment decisions should be guided by indices of asthma control and not only by disease severity. In adults, symptom-based asthma control parameters have been shown to predict exacerbations and health care services use (HSU). We hypothesize that defining asthma control using parent-reported symptoms alone is not adequate in children. Cross-sectional data from the population-based asthma in Canada study were reanalyzed. Random-digit dialing was used to produce the final sample, consisting of 1,001 asthmatics: 801 adults (aged 16+) and 200 children (aged 4-15) participating by parental proxy. Weighted frequencies of Canadian guideline defined asthma control parameters, perceived asthma control, HSU and medication use were calculated separately for adults and children. Stratified analyses compared HSU in controlled versus uncontrolled asthmatics. Over 90% of parents of asthmatic children believed their child's asthma to be controlled. Only 45% were actually controlled as defined by guideline parameters. Among controlled asthmatics, children reported higher HSU (32% reported 2+ health care encounters versus 17% of adults, P < 0.001). Irrespective of control and despite similar use of controller therapy, children reported a higher number of health care encounters than adults (any emergency department visits 37% vs. 24%, P = 0.00003; unscheduled doctor visits 59% vs. 36%, P < 0.00001). While reporting higher HSU, asthmatic children had less frequent episodes of excessive daytime symptoms than adults (29% vs. 49%, respectively, P < 0.0001). Current symptom-based asthma control parameters reported by parental proxy are likely poor predictors of asthma HSU and may not provide adequate asthma control estimates in children.


Can malignant transformation in mature cystic teratoma be preoperatively predicted?
The study aimed to determine whether malignant transformation of mature cystic teratoma (MCT) can be preoperatively predicted by presenting two cases of MCT with malignant transformation and comparing their clinical factors with those of benign MCT encountered at around the same time. Age, maximum tumor diameter, tumor marker levels (serum squamous cell carcinoma (SCC) and carbohydrate antigen (CA) 19-9, the presence of solid tumor masses, and the presence or absence of contrast enhancement in pelvic magnetic resonance imaging (MRI) were investigated in two cases of MCT with malignant transformation and 76 cases of benign MCT in which surgery was performed and a pathological diagnosis given by the department from 2004 to 2010. The mean ages of the two cases with malignant transformation and the cases of benign MCT were 42.5 years and 34.2 years, respectively. The mean maximum diameter of the two tumors with malignant transformation and the cases of benign MCT were 130 mm and 73.6 mm, respectively. The mean serum levels of SCC in the two cases with malignant transformation and the cases of benign MCT were 31.5 ng/ml and 0.92 ng/ml, respectively. Contrast enhancement and the presence of solid masses in images of MCT with malignant transformation were apparent. In order to accurately detect malignant transformation of MCT, the authors found it to be important to determine whether tumors larger than 100 mm in diameter were present and to check for the presence of solid masses enhanced in pelvic MRI examination, as well as to measure at least serum SCC and CA19-9 even in relatively young patients.


Myelin oligodendrocyte glycoprotein antibody-associated disease as a novel presentation of central nervous system autoimmunity in a pediatric patient with Wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene that leads to increased susceptibility to infections, thrombocytopenia, eczema, malignancies, and autoimmunity. Central nervous system (CNS) autoimmune manifestations are uncommon. We describe the case of a five-year-old boy with refractory thrombocytopenia and iron deficiency anemia who developed relapsing bilateral optic neuritis. Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) via serum fluorescence-activated cell sorting assay was positive (titer 1:100), confirming a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). At age six, molecular panel testing for genes associated with primary immunodeficiency identified a missense WAS gene variant. He was subsequently found to have decreased WAS protein expression, consistent with a diagnosis of WAS. This case expands the reported spectrum of CNS autoimmunity associated with WAS and may help to inform long-term therapeutic options.


Perceptions and experiences of nurses and midwives in continuing professional development: a systematic review protocol.
The objective of this systematic review is to explore the perceptions and experiences of nurses and midwives in undertaking continuing professional development.


Immunological evidence for the role of phosphoprotein p68/pI = 7.3 in premessenger RNA splicing.
A 68 kDa (pI = 7.3) nuclear phosphoprotein has been previously characterized as a component of transcriptionally active chromatin. Two-dimensional PAGE Western blotting and radioimmunoassay with monoclonal antibodies have identified this protein in nuclear extracts used for in vitro RNA splicing. In vitro splicing activity could be quantitatively inhibited by preincubating nuclear extracts with the antibodies, but the assembly of 60 S spliceosomes could not.


Do the British Guidelines for Asthma Management facilitate concordance?
Asthma is an example of a common, chronic illness in which clinicians are encouraged to promote concordance and adhere to guidelines. Some existing research suggests that these aims may be incompatible. To describe patient goals for life and for asthma management in order to inform concordance with people with asthma. A cross-sectional, qualitative survey. A purposive sample of 47 adults with asthma from Dundee, UK. The subjects were identified from general practice asthma registers and had a range of ages and asthma severity but no significant comorbidity. Tape-recorded semi-structured interviews. The topic guide was based on the literature and had been piloted in a previous study. The participants focussed on improving their lives, only aiming to improve their asthma as a means of improving their lives. Three aspects of asthma were reported to help or hinder improving life: the use of asthma medication, trigger avoidance and exercise. People integrated these three aspects of asthma in order to maximize life. The study supports the more individualized goals of the recently revised British Guidelines for Asthma Management but highlights the need to develop this further in future revisions. It also provides an explanation for patients' acceptance of less than 'perfect' asthma control and it suggests that shared goals may be achieved in practice by considering the advantages and disadvantages of medication and allergen avoidance on everyday life rather than on asthma.


Effect of immersion in seawater on egg survival in the lizard Anolis sagrei.
Studies on the lizard, Anolis sagrei, revealed that after Hurricane Floyd devastated the Bahamas in 1999, some populations consisted only of hatchlings. Because the storm surge of the hurricane completely inundated these islands, apparently for up to 6 h, survival of anole eggs in salt water for such periods is implied. To test this hypothesis directly, we placed A. sagrei eggs in saltwater for 3 or 6 h with unimmersed eggs serving as the control. Hatching success and incubation time did not differ among the three treatments. These findings help explain the persistence of anole populations on small islands vulnerable to hurricanes.


Effects of polydopamine coatings on nucleation modes of surface mineralization from simulated body fluid.
Polydopamine (PDA) has been recently used as a versatile priming layer for further functionalization of a biomaterial surface, particularly in biomimetic mineralization of biomaterials. Yet most of the existing literature is on inorganic substrates and the underlying effects of the PDA layer coatings on the nucleation and mineralization process and the mineral-substrate interface have not been clearly identified. Here we aimed to investigate the effects of the PDA layer on the nucleation and growth and interfacial morphology of calcium phosphate mineral layer (CaP) from 10× simulated body fluid (10× SBF) on polymeric substrates. It is found that the nucleation of CaP on PDA-coated surface favors a mixed "islanding" and planar growth mode (Stranski-Krastanov) while the "islanding" mode (Volmer-Weber) was observed on the surface without PDA. This different early nucleation stage of mineralization was found to correlate with a more "bonded" interface between the mineral layer and the PDA-coated substrates, a slight increase in the interfacial strength and a different delamination mode. This study therefore provided new insights on how polydopamine priming layer influenced the mineralization process and the interface between the mineral layer and the substrate.


Distribution and factors associated with Salmonella enterica genotypes in a diverse population of humans and animals in Qatar using multi-locus sequence typing (MLST).
Salmonella enterica is one of the most commonly reported causes of bacterial foodborne illness around the world. Understanding the sources of this pathogen and the associated factors that exacerbate its risk to humans will help in developing risk mitigation strategies. The genetic relatedness among Salmonella isolates recovered from human gastroenteritis cases and food animals in Qatar were investigated in the hope of shedding light on these sources, their possible transmission routes, and any associated factors. A repeat cross-sectional study was conducted in which the samples and associated data were collected from both populations (gastroenteritis cases and animals). Salmonella isolates were initially analyzed using multi-locus sequence typing (MLST) to investigate the genetic diversity and clonality. The relatedness among the isolates was assessed using the minimum spanning tree (MST). Twenty-seven different sequence types (STs) were identified in this study; among them, seven were novel, including ST1695, ST1696, ST1697, ST1698, ST1699, ST1702, and ST1703. The pattern of overall ST distribution was diverse; in particular, it was revealed that ST11 and ST19 were the most common sequence types, presenting 29.5% and 11.5% within the whole population. In addition, 20 eBurst Groups (eBGs) were identified in our data, which indicates that ST11 and ST19 belonged to eBG4 and eBG1, respectively. In addition, the potential association between the putative risk factors and eBGs were evaluated. There was no significant clustering of these eBGs by season; however, a significant association was identified in terms of nationality in that Qataris were six times more likely to present with eBG1 compared to non-Qataris. In the MST analysis, four major clusters were presented, namely, ST11, ST19, ST16, and ST31. The linkages between the clusters alluded to a possible transmission route. The results of the study have provided insight into the ST distributions of S. enterica and their possible zoonotic associations in Qatar.


ADP-ribosylation of the rho/rac proteins induces growth inhibition, neurite outgrowth and acetylcholine esterase in cultured PC-12 cells.
Botulinum ADP-ribosyltransferase C3 (C3 exoenzyme) was purified to homogeneity and added to cultured rat pheochromocytoma PC-12 cells. Incubation with this exoenzyme caused inhibition of cell growth and induced neurites as well as acetylcholine esterase in these cells. These changes were dependent on the amount of the enzyme added to the culture, which correlated with the in situ ADP-ribosylation of the rho/rac proteins in the cells. Preincubation with a specific anti-C3 exoenzyme monoclonal antibody inhibited both the ADP-ribosyltransferase activity and the neurite-inducing activity of the enzyme preparation. These results suggest that C3 exoenzyme affected the cellular function of the rho/rac proteins by ADP-ribosylation to induce these changes in the cells.


Influences of trunk muscles on lumbar lordosis and sacral angle.
The strength of abdominal muscle and back extensors or their balances are commonly mentioned as major indicators of potential low back pain (LBP). Former studies on anthropometrics in terms of trunk muscle strength seemed to lack precision in methodology. Furthermore, the extension-flexion ratio, which is a good parameter of trunk muscle balance, was not as much studied as simple maximum torques in this area of study. To investigate relationship between trunk muscle strength and lumbar lordosis, sacral angle in patients who did not show significant abnormal findings on their simple lateral radiograph. Thirty-one subjects were participated and their mean age was 35. Lumbar simple lateral radiograph was taken and lordotic angle was obtained by altered Cobb's method. Sacral angle was also examined on the same film. The relationship between these angles and muscle strength (isometric maximum torques and ratios of them) was investigated by the correlation analysis. None of the isometric maximum torques was related to sacral angle or lordotic angle. However, the ratio of extension to flexion was significantly related to the lordotic angle (Pearson's correlation coefficient=0.491, p<0.01). Other ratios were not related to any of the angles. An imbalance in trunk muscle strength can influence significantly lordotic curve of lumbar spine and might be one risk factor for potential low back pain.


Barriers and facilitators to HIV and syphilis rapid diagnostic testing in antenatal care settings in low-income and middle-income countries: a systematic review.
Testing and treatment during pregnancy is a well-established and cost-effective prevention strategy, which relies largely on use of rapid diagnostic tests (RDTs). Yet, in many low-income and-middle-income countries, the uptake of RDTs is suboptimal. A qualitative meta-synthesis was conducted to identify the barriers and enablers to use of HIV and syphilis RDTs among pregnant women in low-income and middle-income countries. This review was conducted using PRISMA guidelines. Eligible studies included peer-reviewed publications, which used qualitative methods to explore HIV and syphilis RDT in antenatal care clinics in low-income and middle-income countries. Studies focusing on perspectives of pregnant women, healthcare workers and/or stakeholders were included. We used an inductive approach informed by a modified socioecological model to synthesise the data. 62 manuscripts met the eligibility criteria. For pregnant women, initial acceptance of the RDT and continuation in antenatal care depends on the perception that engaging in testing will be a beneficial experience for their baby and themselves, often influenced by the provision of services that are gender-sensitive, confidential, respectful, flexible and considers their well-being into the future. Local sociocultural beliefs about pregnancy and diseases, awareness of diseases and gender roles in society also influenced RDT acceptability among pregnant women. For healthcare workers, the ability to provide high-quality RDT care required ongoing training, accurate and easy to use tests, support from supervisors and communities, sufficient resources and staffing to provide services, and reliable salary. At the stakeholder level, well-developed guidelines and health system infrastructures were imperative to the delivery of RDT in antenatal clinics. Our findings highlight clear gaps to the provision of sustainable and culturally acceptable maternal HIV and/or syphilis screening using RDTs. In addition, greater attention needs to be paid to community stakeholders in promoting the uptake of RDT in antenatal clinics. CRD42018112190.


Costs and benefits of routine hemoglobin A1c screening prior to total joint arthroplasty: a cost-benefit analysis.
Poorly controlled diabetes mellitus (DM) increases the risk for periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). While institutional protocols include hemoglobin A1c (HbA1c) screening in TJA patients, the costs and benefits of routine preoperative screening have not been described. The authors created a decision tree model to evaluate short-term costs and risk reduction for PJIs with routine screening of primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. Probabilities and costs were obtained from published sources. They calculated net costs and absolute risk reduction in PJI for routine screening versus no screening. The authors also performed sensitivity analyses of model inputs including probabilistic sensitivity analyses (PSAs) consisting of 10,000 Monte Carlo simulations. In patients with DM, routine screening before THA resulted in net cost savings of $81 per patient with 286 patients needing to be screened to prevent 1 PJI, while screening before TKA incurred net additional costs of $25,810 per PJI prevented. Routine screening in patients with DM undergoing THA or TKA was cost-saving across 75.5% or 21.8% of PSA simulations, respectively. In patients with no history of DM, routine screening before THA or TKA incurred net additional costs of $24,583 or $87,873 per PJI prevented, respectively. Routine HbA1c screening in patients with DM prior to THA with referral of patients with elevated HbA1c for glycemic optimization may prevent PJI and reduce healthcare costs. In contrast, routine screening in patients with DM prior to TKA or in patients with no history of DM is not cost-saving. Economic Level IV.


Modelling the impact of hailstones on flat steel roofing membranes for residential buildings.
Metal roof panels are commonly used on residential and commercial buildings. Steel panels exposed to hail have not yet been adequately tested for dent resistance. A finite element model (FEM) was used to analyze the entire test setup. To compare artificial hailstones with natural hailstones, which remained intact after impact, different steel sheets were struck by different sizes of artificial hailstones at different terminal velocities. The simulation and the material properties are assessed by comparing the experimental results with the FE model. An equation to predict the dent depth based on kinetic energy and stress is also presented. The results of this study provide a better understanding of the failure modes of hail and roof panels and their effects on dent resistance. In this study, the results of observations and numerical simulations agreed well with those of analytical models. The result is that the proposed equation overestimates the dent depths compared to the dent depths obtained with finite element models, while the equation leads to an underestimation of the dent depths found in the steel sheets.


Trends in birth weight-specific and -adjusted infant mortality rates in Taiwan between 2004 and 2011.
A yearly increase in the proportion of very low birth weight (VLBW) live births has resulted in the slowdown of decreasing trends in crude infant mortality rates (IMRs). In this study, we examined the trends in birth weight-specific as well as birth weight-adjusted IMRs in Taiwan. We linked three nationwide datasets, namely the National Birth Reporting Database, National Birth Certification Registry, and National Death Certification Registry databases, to calculate the IMRs according to the birth weight category. Trend tests and mortality rate ratios in the periods 2010-2011 and 2004-2005 were used to examine the extent of reduction in birth weight-specific and birth weight-adjusted IMRs. The proportion of VLBW (<1500 g) infants among live births increased from 0.78% in 2004-2005 to 0.89% in 2010-2011, thus exhibiting a 15% increase. The extents of the decreases in birth weight-specific IMRs in the 500-999, 1000-1499, 1500-1999, 2000-2499, and 2500-2999 g birth weight categories were 15%, 33%, 43%, 30%, and 28%, respectively, from 2004-2005 to 2010-2011. The reduction in IMR in each birth weight category was larger than the reduction in the crude IMR (13%). By contrast, the IMR in the <500 g birth weight category exhibited a 56% increase during the study period. The IMRs were calculated by excluding all live births with a birth weight of <500 g. The birth weight-adjusted IMRs, which were calculated using a standard birth weight distribution structure for adjustment, exhibited similar extent reductions. In countries with an increasing proportion of VLBW live births, birth weight-specific or -adjusted IMRs are more appropriate than other indices for accurately assessing the real extent of reduction in IMRs.


Anomalous correlation effects and unique phase diagram of electron-doped FeSe revealed by photoemission spectroscopy.
FeSe layer-based superconductors exhibit exotic and distinctive properties. The undoped FeSe shows nematicity and superconductivity, while the heavily electron-doped KxFe2-ySe2 and single-layer FeSe/SrTiO3 possess high superconducting transition temperatures that pose theoretical challenges. However, a comprehensive study on the doping dependence of an FeSe layer-based superconductor is still lacking due to the lack of a clean means of doping control. Through angle-resolved photoemission spectroscopy studies on K-dosed thick FeSe films and FeSe0.93S0.07 bulk crystals, here we reveal the internal connections between these two types of FeSe-based superconductors, and obtain superconductivity below ∼ 46 K in an FeSe layer under electron doping without interfacial effects. Moreover, we discover an exotic phase diagram of FeSe with electron doping, including a nematic phase, a superconducting dome, a correlation-driven insulating phase and a metallic phase. Such an anomalous phase diagram unveils the remarkable complexity, and highlights the importance of correlations in FeSe layer-based superconductors.


The impact of airport characteristics on airport surface accidents and incidents.
Airport surface safety and in particular runway and taxiway safety is acknowledged globally as one of aviation's greatest challenges. To improve this key area of aviation safety, it is necessary to identify and understand the causal and contributing factors on safety occurrences. While the contribution of human factors, operations, and procedures has been researched extensively, the impact of the airport and its associated characteristics itself has received little or no attention. This paper introduces a novel methodology for risk and hazard assessment of airport surface operations, and models the relationships between airport characteristics, and (a) the rate of occurrences, (b) the severity of occurrences, and (c) the causal factors underlying occurrences. The results show for the first time how the characteristics of airports, and in particular its infrastructure and operations, influence the safety of surface operations.


[Impact of nutrition and probiotics on the equine microbiota: current scientific knowledge and legal regulations].
The hindgut microbiota of the horse is a complex structure which can be highly influenced by the diet or nutrients such as starch. For instance, a diet rich in starch promotes the growth of bacteria that can utilize starch and produce lactate while it reduces the growth of fiber fermenting cellulolytic bacteria. Therefore, attempts are made to balance the hindgut microbiota and to minimize the impacts of feeds which are rich in starch such as the supplementation of probiotics. Up to date only different strains of the yeast Saccharomyces cerevisiae (SC) are officially registered probiotics for horses in the European Union. However, studies evaluating the impact of SC supplementation in vivo showed equivocal results in the equine.


A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos.
The segment polarity gene hedgehog (hh) encodes a novel signaling protein that mediates local cell-cell interactions in the developing Drosophila embryo. Here we describe the existence of an hh-related gene family in the zebrafish, Brachydanio rerio. One of these genes, sonic hedgehog (shh), is expressed in the notochord, floor plate, and posterior fin mesoderm, tissues associated with polarizing activities in various vertebrate embryos. The pattern of shh expression in zebra-fish mutants affecting axial structures, together with the consequences of its ectopic expression in normal embryos, is consistent with a role for shh in floor plate induction. By expressing shh in transgenic Drosophila embryos, we also demonstrate a strong functional conservation between the fish and fly hh genes.


Comparison of graft bending angle during knee motion after outside-in, trans-portal and trans-tibial anterior cruciate ligament reconstruction.
To determine graft bending angle (GBA) during knee motion after anatomic anterior cruciate ligament (ACL) reconstruction and to clarify whether surgical techniques affect GBA. Our hypotheses were that the graft bending angle would be highest at knee extension and the difference of surgical techniques would affect the bending steepness. Eight healthy volunteers with a mean age of 29.3 ± 3.0 years were recruited and 3D MRI knee models were created at three flexion angles (0°, 90° and 130°). Surgical simulation of the tunnel drilling was performed with anatomic tunnel position using each outside-in (OI), trans-portal (TP) and trans-tibial (TT) techniques on the identical cases. The models were matched to other knee positions and the GBA in 3D was measured using computational software. Double-bundle ACL reconstruction was analysed first, and single-bundle reconstruction was also analysed to evaluate its effect to reduce GBA. A repeated-measures ANOVA was used to compare GBA difference at three flexion angles, by three techniques or of three bundles. GBA changed substantially with knee motion, and it was highest at full extension (p < 0.001) in each surgical technique. OI technique exhibited highest GBA for anteromedial bundle (94.3° ± 5.2°) at extension, followed by TP (83.1° ± 6.5°) and TT (70.0° ± 5.2°) techniques (p < 0.01). GBA for posterolateral bundle at extension were also high in OI (84.6° ± 7.4°), TP (83.0° ± 6.3°) and TT (77.2° ± 7.0°) techniques (n.s.). Single-bundle grafts did not decrease GBA compared with double-bundle grafts. In OI technique, a more proximal location of the femoral exit reduced GBA of each bundle at extension and 90° flexion. A significant GBA change with knee motion and considerably steep bending at full extension, especially with OI and TP techniques, were simulated. Although single-bundle technique did not reduce GBA as seen in double-bundle technique, proximal location of femoral exits by OI technique, with tunnels kept in anatomic position, was effective in decreasing GBA at knee extension and flexion. For clinical relevance, high stress on graft and bone interface has been suggested by steep GBA at full extension after anatomic ACL reconstruction. Therapeutic study (prospective comparative study), Level II.


Pullulan: an exopolysaccharide and its various applications.
Pullulan is a non-ionic polysaccharide obtained from fermentation of black yeast like Aureobasidium pullulans and is currently exploited in food and pharmaceutical industries due to its unique characteristics. Due to its properties like non-toxic, non-immunogenic, non-carcinogenic, non-mutagenic, pullulan is being explored for various biomedical applications viz., gene delivery, targeted drug therapy, tissue engineering, wound healing, and also being used in diagnostic applications like, perfusion, receptor, and lymph node target specific imaging and vascular compartment imaging. The unique linkage of α (1→4) and α (1→6) in pullulan endows this polymer with distinctive physical traits, including adhesive property and the ability to form fibers. This review article presents an historical outline, overview of properties, production, derivatives of pullulan, its versatile applicability and recent advances of pullulan.


A Comparative Study of Intramuscular Alfaxalone- or Ketamine-Based Anesthetic Mixtures in Gray Squirrels Undergoing Gonadectomy: Clinical and Physiologic Findings.
The gray squirrel is one of the most common invasive species in Europe, whose presence is dangerous for the survival of the European red squirrel. To cope with this biological invasion and to safeguard biodiversity, the LIFE+U-SAVEREDS project aims to protect the red squirrel, by limiting the growth of the current population of gray squirrels and simultaneously promoting their eradication with surgical sterilization. This study compares two different anesthetic protocols, including dexmedetomidine (40 µg/kg) and midazolam (0.3 mg/kg) associated with ketamine (15 mg/kg; n = 25 squirrels) or alfaxalone (5 mg/kg; n = 22 squirrels). A blinded investigator evaluated the quality and onset of sedation, intraoperative anesthesia, and recovery, as well as the physiologic parameters for each animal. Alfaxalone provided a good quality of anesthesia with limited cardiovascular effects (p < 0.05) and good intraoperative myorelaxation. Ketamine induced complete relaxation in a shorter time (p < 0.05) and a rapid (p < 0.001) and excellent (p < 0.05) recovery. Despite the overall superiority of ketamine, alfaxalone appeared to be an adequate alternative anesthetic drug that can be administered without requiring intravascular access. It should be rapidly metabolized and excreted; however, it requires the combination of longer acting sedatives/myorelaxants to prevent a poor recovery quality.


[Blood rheology in chronic arterial occlusive disease as influenced by vasodilators (author's transl)].
Increased blood and plasma viscosity was found in patients with chronic arterial occlusion in comparison with healthy probands. The measurements were done at high and low shear rates. Parenteral pentoxifylline (Trental) lowered blood and plasma viscosity of patients significantly, especially when measured at low shear rates. Application of bencyclane (Fludilat) produced variable results. A definite connection between rheological changes and alterations of the protein fractions in plasma could not be established.


Effects of testosterone, estrogen and progesterone on TNF-α mediated cellular damage in rat arthritic synovial fibroblasts.
Sexual dimorphism is a well-established phenomenon in rheumatoid arthritis, with women exhibiting higher disease severity. Understanding the role of sex hormones using in vivo animal models is limited due to the systemic effects as well as the difficulty in exploring different dose combinations of the hormones simultaneously. However, cell culture systems pose ideal systems for exploring different combinations and concentrations of the hormones simultaneously. In this study, the procedure for isolation of arthritic fibroblasts was standardized using a combination of collagenase and trypsin based on maximal yield and viability after employing different enzymatic disaggregation procedures. The cultured synovial fibroblasts from arthritic rats did not differ significantly from normal rat fibroblasts in terms of proliferation or secretion of inflammatory mediators. Stimulation of fibroblasts with TNF-α was standardized and TNF-α stimulated rat arthritic synovial fibroblasts exhibited an ideal in vitro system for screening antiinflammatory molecules. The effects of physiological and pharmacological concentrations of testosterone, estrogen and progesterone were studied on TNF-α induced cellular damage in rat arthritic synovial fibroblasts. The results showed that estrogen and testosterone exerted antiinflammatory effects on rat arthritic synovial fibroblasts at physiological and pharmacological concentrations. However, there was no significant difference in the effects between physiological and pharmacological concentrations. Progesterone independently did not show any protective effects. In combination with physiological concentrations of estrogen, progesterone abrogated estrogen's protective effect but it exhibited protection in combination with pharmacological concentrations of estrogen.


Successful ablation of a nonreentrant dual atrioventricular nodal tachycardia.
Selective radiofrequency catheter ablation of the slow pathway of the AV node has become the treatment of choice for AV nodal reentrant tachycardia. We describe a case of a nonreentrant AV nodal tachycardia and its successful treatment by slow pathway ablation.


A new antibacterial diterpene from the roots of Salvia caespitosa.
From the roots of Saliva caespitosa Montbret and Aucher ex. Bentham a new diterpene 6beta-hydroxyisopimaric acid (1) has been isolated together with four known diterpenes, one new triterpenoid, 3-acetylvergatic acid (2), as well as five known triterpenoids, two steroids and a flavone. The structures of the compounds were established by spectroscopic analyses. The isolated compounds were tested against standard bacterial strains. Only the new diterpene, 6beta-hydroxyisopimaric acid has strong activity (MIC 9 microg/ml) against S. aureus and (MIC 18 microg/ml) against S. epidermidis as well as against B. subtilis (MIC 9 microg/ml).