Pretreatment with low-dose gadolinium chloride attenuates myocardial ischemia/reperfusion injury in rats.
We have shown that low-dose gadolinium chloride (GdCl3) abolishes arachidonic acid (AA)-induced increase of cytoplasmic Ca(2+), which is known to play a crucial role in myocardial ischemia/reperfusion (I/R) injury. The present study sought to determine whether low-dose GdCl3 pretreatment protected rat myocardium against I/R injury in vitro and in vivo. Cultured neonatal rat ventricular myocytes (NRVMs) were treated with GdCl3 or nifedipine, followed by exposure to anoxia/reoxygenation (A/R). Cell apoptosis was detected; the levels of related signaling molecules were assessed. SD rats were intravenously injected with GdCl3 or nifedipine. Thirty min after the administration the rats were subjected to LAD coronary artery ligation followed by reperfusion. Infarction size, the release of serum myocardial injury markers and AA were measured; cell apoptosis and related molecules were assessed. In A/R-treated NRVMs, pretreatment with GdCl3 (2.5, 5, 10 μmol/L) dose-dependently inhibited caspase-3 activation, death receptor-related molecules DR5/Fas/FADD/caspase-8 expression, cytochrome c release, AA release and sustained cytoplasmic Ca(2+) increases induced by exogenous AA. In I/R-treated rats, pre-administration of GdCl3 (10 mg/kg) significantly reduced the infarct size, and the serum levels of CK-MB, cardiac troponin-I, LDH and AA. Pre-administration of GdCl3 also significantly decreased the number of apoptotic cells, caspase-3 activity, death receptor-related molecules (DR5/Fas/FADD) expression and cytochrome c release in heart tissues. The positive control drug nifedipine produced comparable cardioprotective effects in vitro and in vivo. Pretreatment with low-dose GdCl3 significantly attenuates I/R-induced myocardial apoptosis in rats by suppressing activation of both death receptor and mitochondria-mediated pathways.


Effects of freezing on bone histological morphology.
Allograft bone has been widely used for reconstruction of different portions of the skeleton. The fragment of bone harvested must be kept under low temperatures. The cryopreservation also contributes to decrease the antigenic potential of the tissue. Although this technique is considered safe, there is little information about the morphological modifications that the medullary and cortical portions of bone suffer after freezing. Hence, the aim of this study was to investigate the morphology of bone tissue after freezing under different temperatures and periods. Twelve rabbits were used to analyze the effects of two temperatures, -20 degrees C and -70 degrees C, during four periods of time: 30, 60, 90, 120 days. Tissues were analyzed by HE, picro-sirius stains and also by Feulgen's reaction, through qualitative and morphometric ways, considering the area occupied by cells and nuclei, medullary and cortical portions, as well as by collagen expression at cortical. The differences among the treatments were analyzed by Tukey s test, at 5% significance level. Bone freezing increased cellular and nuclear areas at cancellous bone and diminished nuclear area at the cortical bone. Cortical bone collagen suffered denaturation proportionally to temperature decrease and to freezing duration. These alterations compromised the morphology of tissues after 90 or 120 days of freezing at the temperature of -70 degrees C. Cells necrosed during freezing, contributing to reduce bone antigenicity.


Systematic Review: The Learning Curve for Robot-Assisted Radical Cystectomy-What Do We Know?
Background: The aim of this systematic review is to assess the robot-assisted radical cystectomy (RARC) learning curve (LC), which is important to consider in both risk-benefit assessment and training. Materials and Methods: We performed a systematic literature search using two databases (Medline and Scopus) with the search query "learning AND cystectomy" and included all articles containing data on the assessment of the RARC LC. Our primary outcome was the surgeons' experience (a number of performed procedures) required to achieve the LC plateau. The secondary outcomes related to the methods for assessing the relevant LC. Results: Between 9 and 50 procedures were required to reduce the operation time significantly. The data on estimated blood loss during RARC are somewhat controversial. To optimize the lymph node (LN) yield, it was necessary to treat between 20 and 50 patients. The LC for positive surgical margin was described only in one study, it was completed after 24-30 cases. Between 10 and 15 cases were necessary to reduce length of stay (LOS). Complications became less frequent after 10 to 75 patients but there was no clear plateau in the figures. Conclusions: Based on the relevant assessment criteria, the RARC LC length varies from 10 to 50 cases. The most common criteria for evaluating the learning experience include operation time and the LN yield. Blood loss, length of stay, and complications rate show variable outcomes and may be harder to use systematically as a means of LC assessment.


Analyzing barriers for implementation of public health and social measures to prevent the transmission of COVID-19 disease using DEMATEL method.
COVID-19 is a contagious disease caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Till now there are no vaccines and explicit medicines available for the treatment of COVID-19 disease, therefore the initiatives like public health and social measures are helpful in limiting the quantity of contaminations and saving lives. Keeping this in view, an attempt has been made in the present work to identify the barriers which hinder the implementation of these public health and social measures METHODS: The barriers to implement public health and social measures for preventing transmission of COVID-19 are identified using systematic literature review and these barriers are then categorized using Decision-making trial and evaluation laboratory (DEMATEL) method. Results reveal that among ten identified barriers, Lack of resources for implementing public health and social measures is found to be the most influential barrier to implement public health and social measures for preventing transmission of COVID-19. The successful implementation of public health and social measures depends on the adequate availability of resources which include medical equipment, personnel and financial dealings. The outcome of this research work will benefit and motivate the higher authorities to consider and overcome various challenges to prevent the transmission of COVID-19.


Flow rate calibration to determine cell-derived microparticles and homogeneity of blood components.
Cell-derived microparticles (MPs) are currently of great interest to screening transfusion donors and blood components. However, the current approach to counting MPs is not affordable for routine laboratory use due to its high cost. The current study aimed to investigate the potential use of flow-rate calibration for counting MPs in whole blood, packed red blood cells (PRBCs), and platelet concentrates (PCs). The accuracy of flow-rate calibration was investigated by comparing the platelet counts of an automated counter and a flow-rate calibrator. The concentration of MPs and their origins in whole blood (n=100), PRBCs (n=100), and PCs (n=92) were determined using a FACSCalibur. The MPs' fold-changes were calculated to assess the homogeneity of the blood components. Comparing the platelet counts conducted by automated counting and flow-rate calibration showed an r2 of 0.6 (y=0.69x+97,620). The CVs of the within-run and between-run variations of flow-rate calibration were 8.2% and 12.1%, respectively. The Bland-Altman plot showed a mean bias of -31,142platelets/μl. MP enumeration revealed both the difference in MP levels and their origins in whole blood, PRBCs, and PCs. Screening the blood components demonstrated high heterogeneity of the MP levels in PCs when compared to whole blood and PRBCs. The results of the present study suggest the accuracy and precision of flow-rate calibration for enumerating MPs. This flow-rate approach is affordable for assessing the homogeneity of MPs in blood components in routine laboratory practice.


Avulsion of the ureter from both ends as a complication of interruption of pregnancy with vacuum aspirator.
A case of avulsion of a ureter from the pelvioureteral junction and its discharge through the vagina during an attempt to interrupt pregnancy by suction is presented. The preoperative and operative findings are described, as well as the mechanism that caused this kind of trauma. The proposed management of such a case is discussed.


[Delaire's facial mask in the treatment of anterior prognathic anomalies].
The authors present the technique of treatment of pseudo Class III malocclusion using an orthopedic Delaire's face mask. The use of the method is illustrated with 3 clinical cases.


Detection of toxigenic Escherichia coli using biotin-labelled DNA probes following enzymatic amplification of the heat labile toxin gene.
Several types of DNA probes labelled with biotin were compared for their sensitivity to detect the heat labile toxin (LT) gene in toxigenic Escherichia coli. In addition, a procedure was developed for enzymatically amplifying LT gene sequences in toxigenic E. coli. Probes were labelled with biotinylated nucleotides by either nick translation; 3' tailing; primer extension of probe DNA cloned into bacteriophage M13; sandwich hybridization; or oligolabelling of isolated DNA fragments. A single stranded probe consisting of a DNA fragment from the LT gene cloned into the bacteriophage M13mp18 and detected by hybridization to oligolabelled biotinylated M13mp18 RF DNA in a sandwich hybridization was able to detect as little as 10 pg of toxin gene DNA. Cloned LT gene DNA was serially diluted and amplified enzymatically using synthetic oligonucleotide primers. Amplified DNA was detected using biotin-labelled M13-based probes. As little as 1 fg of LT DNA could be amplified to detectable levels by this method. Experiments with LT+ bacteria resulted in the detection of as few as 1000 bacteria. The combination of enzymatic amplification coupled with M13-based DNA probes provides a highly sensitive tool for detecting pathogenic microorganisms.


The inhibition of phosphatidylinositol 3-kinase by quercetin and analogs.
Phosphatidylinositol (PtdIns) 3-kinase is an enzyme involved in cellular responses to growth factors. Quercetin (2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyrano-4-one), a naturally occuring bioflavinoid, was found to inhibit PtdIns 3-kinase with an IC50 of 1.3 micrograms/ml (3.8 microM); inhibition appears to be directed towards the ATP binding site of the kinase. Analogs of quercetin were also investigated as PtdIns 3-kinase inhibitors, with the most potent compounds exhibiting IC50's in the range of 1.7-8.4 micrograms/ml (5-19 microM). In contrast, genistein, a potent tyrosine kinase inhibitor of the isoflavone class, did not inhibit PtdIns 3-kinase significantly (IC50 greater than 30 micrograms/ml). These findings suggest that flavinoids may serve as potent inhibitors of PtdIns 3-kinase. Furthermore, the enzyme is much more sensitive to substituents at the 3-position of the flavinoid ring than are other protein and PtdIns kinases, suggesting that specific inhibitors of PtdIns 3-kinase can be developed to explore the biological role of the enzyme in cellular proliferation and growth factor response.


Gender differences in autotomy following sciatic cryoneurolysis in the rat.
Gender differences reported in nociceptive and nerve injury research should be considered before conclusions about basic pathologic mechanisms are drawn. Holtzman male rats are routinely used in the mononeuropathy model produced by a peripheral nerve freeze lesion, sciatic cryoneurolysis (SCN). SCN reproducibly results in abnormal behaviors which include autotomy, the gnawing and scratching of the affected hindpaw. In the present studies, the incidence and severity of autotomy 1 to 21 days following SCN was compared in male and female Holtzman rats. Female Holtzman rats displayed a decreased incidence and severity of autotomy 7 days and beyond following SCN. This disparity was statistically different at 14 days (p < 0.01) and at 21 days (p < 0.05) by Newman-Keuls test. Morphometric comparison of the sciatic nerve at the lesion site in male and female rats 14 days post-SCN (time of peak autotomy behavior in this model) displayed differences in the fascicular percentage of edema (p < 0.01) and remyelinating axons (p < 0.05) between genders using Student's t-test. However, these percentage values did not correlate with either the incidence or severity of autotomy scores for those animals. Therefore, biochemical differences at and/or proximal to the peripheral nerve freeze lesion may be responsible for mechanisms which generate or relate to autotomy.


A reply to Kausler: to rehearse or not to rehearse; was that our question?
A reply is made to criticisms by Kausler of a previous study by these authors. Two main points are discussed: the main thrust of the previous study and the use of the concept "rehearsal deficit". Suggestions for testing a specific rehearsal deficit hypothesis are given.


Nanostructured conjugates from tara gum and α-lactalbumin. Part 1. Structural characterization.
Nanostructures from conjugates of tara gum and α-lactalbumin were obtained via the heat-gelation process with pH adjustment. The conjugates were produced by Maillard reaction using the dry-heating method in lyophilized or spray-dried mixtures of TG and α-la and were characterized by browning index (BI) and percentage of free amino groups (% FAG). Nanostructured systems were characterized by dynamic light scattering, ζ-potential, circular dichroism, and intrinsic fluorescence to evaluate the structures. The most appropriate time of conjugation was 2 days. The spray-dried and lyophilized mixtures presented different values of BI and % FAG (p < 0.05), indicating that the glycosylation was more intense in lyophilized mixtures. Nanostructures with average sizes lower than 300 nm were formed under different conditions of temperature, pH, and heating time. Analyses of circular dichroism and intrinsic fluorescence showed conformational changes in the nanostructures, mainly a decrease in the α-helix content in spray-dried systems. The characteristics presented by the studied systems showed that it is possible to obtain nanostructures from conjugates of tara gum and α-lactalbumin.


Amyloid beta accumulation in TgF344-AD rats is associated with reduced cerebral capillary endothelial Kir2.1 expression and neurovascular uncoupling.
Alzheimer's disease (AD) exerts a tremendous socio-economic burden worldwide. Although reduced cerebral blood flow is an early and persistent symptom that precedes the loss of cognitive function in AD, the underlying molecular and cellular mechanisms remain unclear. The present study investigated whether capillary endothelial inward rectifier potassium 2 (Kir2.1) expression is reduced in TgF344-AD (AD) rats and contributes to neurovascular uncoupling and cognitive deficits in AD. Three- to fourteen-month-old AD rats expressing mutant human APP and PS1 and age-matched wild-type (WT) F344 rats were studied. AD rats exhibited higher amyloid beta (Aβ) expression in the brain as early as 3 months of age and amyloid plaques by 4 months of age. Functional hyperemic responses induced by whisker stimulation were impaired at 4 months of age, which were exacerbated in 6-month- and 14-month-old AD rats. The expression of Kir2.1 protein was significantly lower in the brains of 6-month-old AD versus WT rats, and Kir2.1 coverage was lower in the cerebral microvasculature of AD than in WT rats. Aβ1-42 reduced the Kir2.1 expression in cultured capillary endothelial cells. Cerebral parenchymal arterioles with attached capillaries exhibited a reduced vasodilator in response to 10 mM K+ applied to capillaries, and constricted less following administration of a Kir2.1 channel blocker, compared to WT vessels. These results indicate that capillary endothelial Kir2.1 expression is reduced and contributes to impaired functional hyperemia in AD rats at early ages, perhaps secondary to elevated Aβ expression.


Updates on Stress Imaging Testing and Myocardial Viability With Advanced Imaging Modalities.
Non-invasive stress testing plays a key role in diagnosis and risk stratification in patients with coronary artery disease. Technical advances in CT, MRI, and PET have lead to increased utility of these modalities in myocardial perfusion imaging. The aim of the review is to provide a succinct update on CT, PET, and MRI for myocardial stress perfusion imaging.


A phosphorylethanolamine-functionalized super-hydrophilic 3D graphene-based foam filter for water purification.
A phosphorylethanolamine-functionalized graphene foam (PNGF) has been proposed as an active filtration material for the capture and removal of heavy metal ions in water. Benefiting from its abundant hydrophilic portion of oxygen, nitrogen and phosphorus groups, the PNGF is super-hydrophilic. The selected heavy metal ions, Pb(II) and Cd(II), could be rapidly and efficiently absorbed within 10min using the PNGF through a filtration model, which is obviously less time compared with the several hours or even longer time when employing the traditional shaking or stirring model. In addition, the used PNGF filters can be easily reused after a simple, low-cost detachment using HCl to remove the heavy metals, providing a new approach for water purification.


Sequence and expression of the chicken calcitonin gene.
The avian calcitonin gene was isolated and sequenced; two mRNAs are expressed by tissue-specific alternate splicing. The peptides encoded by the mRNAs are the protein precursors of either calcitonin or calcitonin gene-related peptide (CGRP). Calcitonin is expressed predominantly in ultimobranchial bodies and CGRP in brain.


What Is the Efficacy of Teaching Psychotherapy to Psychiatry Residents and Medical Students?
Because there are no formal reviews, the authors set out to identify and evaluate studies on teaching psychotherapy to psychiatry residents and medical students. PubMed, Embase, and PsycINFO were searched for papers with outcomes on teaching psychotherapy. Search terms included psychotherapy, teaching, residents, medical students, supportive, psychodynamic, cognitive, behavioral, learning, training, skills, competency, and mentalization. Nine studies were found that met inclusion criteria. There were seven studies of psychiatry residents and two of medical students. Only two of the research designs had comparison groups, and these were both randomized controlled trials, while seven of the other designs were pretest and posttest. Teaching methods, course content, and outcome measures varied widely across studies. Common methodological problems included a lack of control, low numbers of subjects as learners, and a lack of validity of the outcome measures. Only one of the studies was judged to be methodologically rigorous. These findings establish a priority for undertaking additional rigorously designed studies in evaluating the teaching of psychotherapy to psychiatry residents and medical students.


Histological features of peritoneal lavage with ropivacaine in rats with fecal peritonitis.
To evaluate the histological features in lungs, peritoneum and liver of rats subjected to fecal peritonitis and treated with peritoneal lavage with 0.2% ropivacaine. Twenty Wistar rats were subjected to laparotomy 6 h after the fecal peritonitis induction with autogenous stool. Rats were randomly distributed into 4 groups: I - (n=5) Control, no treatment; II - (n=5) Drying of the abdominal cavity; III - (n=5) Abdominal cavity lavage with 3 ml 0.9% saline solution and drying; and IV - (n=5) Abdominal cavity lavage with 3 ml 0.2% ropivacaine and drying. The animals that died underwent necropsy, and the surviving ones were subjected to euthanasia on the 11th day post-surgery. Fragments of liver, lungs and peritoneum were removed for histological evaluation. The animals that received peritoneal lavage (groups III and IV) showed greater survival than the drying and control groups. Lavage with ropivacaine prevented death during the observed period. Peritoneal lavage with ropivacaine maintained the architecture of the lung, peritoneum and liver without any important histological alterations. The histopathological findings analyzed correlated with greater survival of group IV. Treatment of fecal peritonitis in rats with peritoneal lavage using 0.2% ropivacaine demonstrated a reduction in histopathological alterations related to inflammatory response and sepsis.


[Exogenously induced retinopathies].
Exogenously induced retinopathies can be caused by consumation of stimulating substances, systemic or ocular medications, vaccinations, light or irradiation. Some of the effects are transient, whereas other effects induce irreversible toxic reactions. Retinal damage may develop either acutely with obvious relation to the damaging cause, but often may take a long duration of repeated use of a substance or medication. External stimulants (e.g. nicotine, alcohol, poppers, methanol) are the most frequent cause of exogenously induced retinal damage. Side effects from systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK-, ERK-, FLT3-, checkpoint inhibitors, didanosin, pentosanpolysulfat sodium) or intravitreally applied drugs (e.g. antibiotics, VEGF-inhibitors) are less frequent. Ocular side effects associated with vaccinations are rare. Ambient light sources induce no damaging effects on the retina. Incorrect use of technical or medical light sources (e.g. laser pointers) without adherence to safety recommendations or unshielded observation of the sun might induce permanent retinal damage. Local or external irradiation might induce retinal vascular damage resulting in radiation retinopathy.


Singlet oxygen and non-photochemical quenching contribute to oxidation of the plastoquinone-pool under high light stress in Arabidopsis.
The redox state of plastoquinone-pool in chloroplasts is crucial for driving many responses to variable environment, from short-term effects to those at the gene expression level. In the present studies, we showed for the first time that the plastoquinone-pool undergoes relatively fast oxidation during high light stress of low light-grown Arabidopsis plants. This oxidation was not caused by photoinhibition of photosystem II, but mainly by singlet oxygen generated in photosystem II and non-photochemical quenching in light harvesting complex antenna of the photosystem, as revealed in experiments with a singlet oxygen scavenger and with Arabidopsis npq4 mutant. The latter mechanism suppresses the influx of electrons to the plastoquinone-pool preventing its excessive reduction. The obtained results are of crucial importance in light of the function of the redox state of the plastoquinone-pool in triggering many high light-stimulated physiological responses of plants.


Detrusorectomy reduces the need for augmentation and use of antimuscarinics in children with neuropathic bladders.
To assess bladder behaviour and long-term outcome after detrusorectomy in children. Between 1990 and 2001, 49 detrusorectomies were performed (mean follow-up: 9.6 years) in children with neuropathic bladders (mean age at surgery: 9.8 years). Urodynamic study (UDS) was done before surgery (pre-UDS) and after surgery (UDS-1 and UDS-2). Bladder behaviour was assessed as good, fair or poor depending on the volume and intravesical pressure. In all patients, oxybutynin and clean intermittent catheterization were used preoperatively. In 24 patients, good bladder compliance and capacity were seen before detrusorectomy. Good and fair outcomes were observed in 35 (71%) patients at 1 year and in 39 (79%) patients 6 years after detrusorectomy. In 30 (60%) patients, there was hardly any difference between the first and second follow-up. In 9 (18%) patients, formal bowel bladder augmentation was necessary: in 6 (12%) because of poor compliance and in 3 because of small bladder volume and incontinence. Seven patients improved during follow-up, 5 of them after resuming oxybutynin. In 11 patients, oxybutynin could be stopped, and in 2 the dosage could be reduced to once daily. The good short-term results of detrusorectomy generally remain unchanged at long-term follow-up. Detrusorectomy can reduce the need for antimuscarinics, and the need for formal bladder augmentation in selected cases.


Quantitative matrix-assisted laser desorption/ionization mass spectrometry for the determination of enzyme activities.
Quantitative matrix-assisted laser desorption/ionization (MALDI) time-of-flight (ToF) mass spectrometry (MS) was applied for the determination of concentrations of low-molecular-weight (< 400Da) substrates and products of enzyme-catalyzed reactions. Isotope-labeled and fluorinated internal standards were used for the quantification. Automated quantitative MALDI-ToF MS analysis of quenched samples allowed the direct and simultaneous observation of time-dependent decrease of substrate concentration and increase of product concentration without any need for prepurification or desalting steps. The results showed good agreement with established but more elaborate analytical methods. MALDI-ToF MS thus is an interesting alternative tool for the determination of enzyme activities. Due to automated and miniaturized measurement it is especially suitable for the screening of biocatalysts.


A review of measured bioaccumulation data on terrestrial plants for organic chemicals: Metrics, variability, and the need for standardized measurement protocols.
Quantifying the transfer of organic chemicals from the environment into terrestrial plants is essential for assessing human and ecological risks, using plants as environmental contamination biomonitors, and predicting phytoremediation effectiveness. Experimental data describing chemical uptake by plants are often expressed as ratios of chemical concentrations in the plant compartments of interest (e.g., leaves, shoots, roots, xylem sap) to those in the exposure medium (e.g., soil, soil porewater, hydroponic solution, air). These ratios are generally referred to as "bioconcentration factors" but have also been named for the specific plant compartment sampled, such as "root concentration factors," "leaf concentration factors," or "transpiration stream (xylem sap) concentrations factors." We reviewed over 350 articles to develop a database with 7049 entries of measured bioaccumulation data for 310 organic chemicals and 112 terrestrial plant species. Various experimental approaches have been used; therefore, interstudy comparisons and data-quality evaluations are difficult. Key exposure and plant growth conditions were often missing, and units were often unclear or not reported. The lack of comparable high-confidence data also limits model evaluation and development. Standard test protocols or, at a minimum, standard reporting guidelines for the measurement of plant uptake data are recommended to generate comparable, high-quality data that will improve mechanistic understanding of organic chemical uptake by plants. Environ Toxicol Chem 2018;37:21-33. © 2017 SETAC.


Intrasphenoidal encephaloceles--a clinical entity.
In the current classification basal encephaloceles are grouped together with real transsphenoidal encephaloceles. But those encephaloceles extending only into but not through the sphenoid sinus seem to represent a specific clinical entity and therefore should be regarded as a rare subgroup of sphenoidal encephaloceles. One personal case and six cases from the literature are reviewed, the own case being associated with an empty sella turcica. The initial sign is rhinorrhea, almost invariably. The association with other intracranial anomalies is uncommon. The extradural transsphenoidal or transethmoidal midline approach accompanied by a shunting procedure today is the most suitable method of surgical treatment.


Serum concentration of interleukin-18 is up-regulated in patients with ANCA-associated vasculitis.
We investigated circulating interleukin-18 concentrations in patients with ANCA-associated vasculitis (ASV) and healthy control subjects, and included a group of hemodialysis patients, a patient group previously reported to show high IL-18 plasma levels. Anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) serum levels were also measured. Interestingly we found significantly increased serum IL-18 concentrations in ASV patients as compared to healthy controls, 437 vs. 185 pg/ml (p < 0.0001). The increase of IL-18 production was similar irrespective of presence of autoantibodies to PR3 or MPO. As expected the hemodialysis patients also showed significantly increased circulating IL-18 concentrations as compared to control subjects.


Porencephaly: computed tomography (CT) scan findings.
Twenty-six cases of porencephalic cysts were analyzed. The cysts were multiple in 26.9% and were associated with subarachnoid cysts in 11.5%. The main presentations were seizures, cerebral palsy and mental retardation. The unifocal cysts were mainly in the frontoparietal region, suggesting a congenital aetiology. Multiple cysts were noted in the basal ganglia region. A case of multiloculated cysts, of unknown aetiology, is noted. The aetiology of multifocal porencephaly and a diagnostic method of differentiating congenital from acquired porencephaly are discussed.


Biochemical pathogenesis of demyelination in globoid cell leukodystrophy (Krabbe's disease): the effects of psychosine upon oligodendroglial cell culture.
The effects of psychosine on the metabolism of myelin associated glycolipids such as galactocerebroside and sulfatide in mouse brain cell cultures were investigated in order to clarify the mechanism of demyelination in globoid cell leukodystrophy (Krabbe's disease). The incorporation of 3H-galactose into cerebroside and sulfatide was studied in the presence of psychosine (1-3 micrograms/ml medium). These data indicated that psychosine inhibited the incorporation of 3H-galactose into cerebroside and sulfatide not in astroglial cell culture but in oligodendroglial cell culture. Oligodendrocytes produce myelin in the central nervous system, and cerebroside and sulfatide are major components of myelin. These results suggest that psychosine influences the lipid metabolisms of myelin and subsequently leads to the demyelination in Krabbe's disease.


New compounds: isoquinoline derivatives as simple emetine models.
Several new isoquinolines were prepared using Reissert compounds. A few compounds were screened, and they exhibited no antineoplastic activity.


Gentle yet effective treatment for elderly patients with refractory or relapsing multiple myeloma.
Fourteen patients, aged 65-85 years, with refractory (11) or relapsing (3) multiple myeloma were treated with a "protracted-sequential" protocol comprising vincristine 1-2 mg or vindesine 3 mg/M(2) (max. 5 mg) IVI over 4 hr on D1, prednisolone 40-50 mg PO D1-14, and melphalan 2-4 mg PO or cyclophosphamide 50-100 mg PO D15-28; cycles were repeated at 4-6 weekly intervals. Treatment was continued for 12 months if the response was optimal or indefinitely if the response was suboptimal. Five patients responded optimally; their survival from the commencement of this protocol ranged from 30 to 120 months. The other nine patients achieved a partial response, their survival ranging from 4+ to 79 months. The treatment is simple, nontoxic, and as convenient as the "classic combination" of melphalan and prednisolone.


Maternal views on infant hearing loss in a developing country.
Parental support for infant hearing loss is essential for a successful infant screening programme. However, in developing countries where unfavourable customs and beliefs towards childhood disabilities have been reported, parental support towards infant screening is uncertain and there is presently no published evidence on the subject. To elicit the views of mothers and would-be mothers in order to ascertain their knowledge on infant hearing loss and their attitudes towards infant hearing screening. A structured questionnaire consisting of 15 questions was administered to 101 mothers (mean age 31.6+/-7.3 years, range: 21-55 years) attending two community hospitals in Lagos, Nigeria. The responses were evaluated by descriptive statistics, factor analysis of the principal components and multiple regression analysis. The reliability of the two main domains (knowledge and attitude) was tested for internal consistency by Cronbach's alpha coefficient. Maternal knowledge was highest for measles (73%; mean score 2.54) and ear discharge (73%; mean score 2.51) but low for birth asphyxia (37%; mean score 1.90), traditional medicine (42%; mean score 2.03) and jaundice (47%; mean score 2.09) as causes of hearing loss. Attitude towards neonatal screening was positive in majority of mothers (92%; mean score 2.84) and there was a high acceptance of hearing aids as an early intervention option (84%; mean score 2.70). Five factors (eigenvalue>1) were extracted after principal component analysis with the attitude variables loading highly and exclusively on one factor. Age was the only demographic variable that was associated with a domain (knowledge) after multiple regression analysis. The component scales for the two domains were highly internally consistent (alpha coefficients of 0.84 and 0.83). Contrary to the concerns often expressed about parental support for infant hearing screening programmes in developing countries, this study suggests that current parental knowledge and attitude favour early detection and intervention of childhood hearing impairment.


Mixer-settler counter-current chromatography with multiple spiral disk assembly.
A novel system for performing high-speed counter-current chromatography has been developed for separation of biopolymers using polymer phase systems. The spiral disk assembly consisting of eight units, each equipped with over 300 mixer-settler sets, was constructed and performance evaluated in terms of retention of the stationary phase and separation efficiency. A series of experiments was performed with a polymer phase system composed of polyethylene glycol 1000 (12.5%, w/w) and dibasic potassium phosphate (12.5%, w/w) using two stable protein samples of myoglobin and lysozyme at various experimental conditions of flow rates and revolution speeds. The best results were obtained with revolution speeds of 800-1000rpm at flow rates of 0.25-0.5ml/min where the partition efficiency of several 100 theoretical plates was achieved with over 50% stationary phase retention.


Effectiveness and safety of intravenous amiodarone in drug-resistant tachyarrhythmias of children.
Experience with pediatric use of intravenous amiodarone is limited. In this study, our experiences with intravenous amiodarone in children with acute life-threatening or chronic tachyarrhythmias are reviewed. Twelve patients, with a mean age of 3.4 +/- 3.1 years, range 9 months-10 years (two with incessant ventricular tachycardia, one with ectopic atrial tachycardia, two with atrioventricular re-entrant tachycardia (three episodes), four with postoperative or congenital junctional ectopic tachycardia, two with bradycardia-tachycardia syndrome, one with atrial tachycardia) were treated with intravenous amiodarone during 13 tachycardia episodes. Left ventricular systolic functions were depressed in six patients. In 11 patients, a median of two drugs (range one-four), including adenosine infusion and in five cases direct current cardioversion were tried without success prior to intravenous amiodarone. The loading dose of amiodarone was 5 mg/kg in all episodes, infused over 1 h. Maintenance infusion was required in 12 episodes. In 10 episodes (77%), amiodarone was considered effective, in one (7.6%) partially effective (junctional ectopic tachycardia) and in two (15.4%) ineffective (sick sinus syndrome, atrial tachycardia). Therapeutic effect was obtained in a median period of 30 h (range 1-103 h). The mean effective maintenance dose was 10 +/- 4.7 micrograms/kg per min (range 5-15 micrograms/kg per min). In one patient, mild hypotension, and in three patients cellulitis occurred, but none of them necessitated termination of treatment. Intravenous amiodarone is found to be an effective and safe antiarrhythmic agent for children with acute life-threatening and chronic tachyarrhythmias and depressed left ventricular systolic functions.


Key factors for abating particulate matter in a highly industrialized area in N Spain: Fugitive emissions and secondary aerosol precursors.
In highly industrialized areas, abating particulate matter (PM) is complex owing to the variety of emission sources with different chemical profiles that may mix in the atmosphere. Gijón-an industrial city in northern Spain-was selected as a case study to better understand the key emission sources and improve air quality in highly industrialized areas. Accordingly, the trends of various air quality indicators (PM10, PM2.5, SO2, NO2, and O3) during the past decade (2010-2019) were analyzed. Additionally, the inorganic and organic PM10 compositions were analyzed for source apportionment studies and to assess the impact of COVID-19 restrictions on PM10 levels. The results revealed that over the past decade, PM10 concentrations decreased, whereas PM2.5 concentrations dominated by secondary inorganic aerosols (SIA) remained relatively constant. Notably, during the COVID-19 lockdown, the PM10 concentration increased by 9.1%, primarily owing to an increase in regional SIA (>65%) due to specific meteorological conditions that favor the formation of secondary PM from gaseous precursors. Overall, eight key PM10 sources were identified: "industrial fugitive PM resuspension" (FPM, 28% of mean PM10 concentration), "aged sea spray" (SSp, 16%), "secondary nitrate" (SN, 15%), "local diffuse source" (LPM, 12%), "solid fuel combustion" (SFC, 7.8%), "biomass burning" (BB, 7.4%), "secondary sulphate" (SSu, 6.0%), and "sinter" (SIN, 4.5%). The PM10 concentration in Gijón is significantly influenced by the integrated steel industry (FPM, SFC, and SIN; 41% of PM10) and fugitive primary PM emissions were the main source (FPM and LPM; 40%). To reduce PM10 and PM2.5 concentrations, industrial fugitive emissions, which are currently poorly regulated, and SIA precursors must be abated. This study provides a methodological approach that combines trend analysis, chemical speciation, and source apportionment for assessing pollution abatement strategies in industrialized areas with a complex mix of emission sources.


Zika Virus and the Rio Olympic Games.
To evaluate the impact of Zika virus on preparation and management of the New Zealand (NZ) Olympic team. Descriptive manuscript. New Zealand Olympic Health team preparation and management during the Rio de Janeiro Olympic Games, 2016. New Zealand Olympic Team members. This manuscript describes the approaches used by the NZ Olympic Health team to the minimization of risk from Zika virus. Although descriptive of approach forms most of the article, the results of Zika virus serology are presented. The NZ Olympic Health team took a proactive approach to risk mitigation, including extensive education, clothing changes, mosquito spray, mosquito nets, and voluntary postexposure testing. No positive serology was observed in those tested. The outbreak of Zika virus in Brazil, the associated complication of microcephaly, and the evolving understanding of virus transmission created significant uncertainty for NZ Olympic team members. The proactive approach taken by the health team to the mitigation of risk, combined with the anticipated low risk of arbovirus transmission over the period of the games, resulted in enhanced confidence from team members and no reports of positive serology.


Distribution and chromatographic characterisation of CGRP-like immunoreactivity in the brain and gut of the rat.
Radioimmunoassay, chromatography and immunocytochemistry were used to study the occurrence of calcitonin gene-related peptide in the brain and gastrointestinal tract of the rat. In the brain, the highest concentrations of the peptide were found in the medulla oblongata (58.3 +/- 6.8 pmol/g) where immunocytochemistry showed the presence of immunoreactive cell bodies. Significant concentrations were also found in the pancreas and throughout the gastrointestinal tract, the highest levels occurring in the pyloric sphincter (48.0 +/- 6.0 pmol/g). CGRP-like immunoreactivity in the gastrointestinal tract was restricted to nerve fibers. Chromatographic analysis of the CGRP-like immunoreactivity occurring in these tissues showed that at least 70% was indistinguishable from the synthetic peptide. However, there was also evidence of a number of smaller cross-reacting molecular species.


Postoperative comparison of the results from use of antibiotic prophylaxis for one and five days among patients undergoing lumbar arthrodesis.
To compare the postoperative results from use of antibiotic prophylaxis for one and five days among patients undergoing lumbar arthrodesis at up to three levels. Forty-three patients who all underwent lumbar arthrodesis due to degenerative disc disease at one, two or three levels were evaluated. They were divided randomly into two groups: one received antibiotic prophylaxis with cefalotin (1 g) and the other received the same antibiotic for five days. After the surgical intervention, the patients were evaluated at the time of hospital discharge, at the first return to the clinic (two weeks later) and 90 days after the date of the surgery with the surgical wound, with clinical examination of the surgical wound and laboratory tests on both groups. It was observed that among the patients in the group with one day of antibiotic prophylaxis, 28.6% presented complications in the surgical wound, while in the group with five days, 27.9% presented complications. This study demonstrates that a single dose of antibiotic prophylaxis is as effective as a regimen of multiple doses in lumbar arthrodesis surgery at up to three levels. Thus, the costs and risks of subjecting patients to hospitalization under a prolonged drug regimen are unjustifiable.


Differential neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Swiss-Webster mice from different sources.
Male Swiss-Webster mice obtained from three different commercial suppliers were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice from one of the three suppliers were considerably more sensitive to the neurotoxic effects of MPTP than mice from the others. For example the MPTP-induced decrements in the neostriatal levels of dopamine and its metabolites, which are a reflection of the neurotoxic process, were considerably greater in the sensitive strain than in the less sensitive strains.


Intramural pseudodiverticulosis of the esophagus: a case report.
Esophageal intramural pseudodiverticulosis (EIPD) is a rare disorder in adults, and even more in infants and children. It is characterized by the dilatation of the submucosal esophageal glands. The exact etiology and pathophysiology of EIPD is, however, unknown. Dysphagia is the predominant presenting symptom in both children and adults. Here, we present a case of a boy with persistent dysphagia who had a thorough diagnostic workup and was eventually diagnosed with EIPD.


Lyotropic Boron Nitride Nanotube Liquid Crystals: Preparation, Characterization, and Wet-Spinning for Fabrication of Composite Fiber.
Microfiber fabrication via wet-spinning of lyotropic liquid crystals (LCs) with anisotropic nanomaterials has gained increased attention due to the microfibers' excellent physical/chemical properties originating from the unidirectional alignment of anisotropic nanomaterials along the fiber axis with high packing density. For wet-spinning of the microfibers, however, preparing lyotropic LCs by achieving high colloidal stability of anisotropic nanomaterials, even at high concentrations, has been a critically unmet prerequisite, especially for recently emerging nanomaterials. Here, we propose a cationically charged polymeric stabilizer that can efficiently be adsorbed on the surface of boron nitride nanotubes (BNNTs), which provide steric hindrance in combination with Coulombic repulsion leading to high colloidal stability of BNNTs up to 22 wt %. The BNNT LCs prepared from the dispersions with various stabilizers were systematically compared using optical and rheological analysis to optimize the phase behavior and rheological properties for wet-spinning of the BNNT LCs. Systematic optical and mechanical characterizations of the BNNT microfibers with aligned BNNTs along the fiber axis revealed that properties of the microfibers, such as their tensile strength, packing density, and degree of BNNT alignment, were highly dependent on the quality of BNNT LCs directly related to the types of stabilizers.


The membrane proteins of the overloaded and senescent heart.
Cardiac hypertrophy which occurs during chronic mechanical overload is one of the numerous examples of biological adaptation to environmental requirements. As such, it is obtained at random by trial and error, and adaptation represents the sum of various modifications in gene expression, including the shift in isoform of myosin or in iso Na+, K+ ATPase, the decrease in beta-adrenergic and muscarinic receptors, ryanodine channels or SR Ca2+ ATPase densities and the unchanged density in Ca2+ current. Some of these changes are beneficial at the cellular level, but are finally detrimental for the organism as a whole, as is the slowing of Vmax. It was suggested that the calcium homeostasis of the hypertrophied cardiocyte was fragile and that this modified cell was less able to buffer the changes in the intracellular calcium, thus providing a biological basis for the arrhythmogenicity of the hypertrophied heart. These various modifications may provide a new key for future pharmaceutical research.


Antitumor effect of selected daunorubicin derivatives in mice with P 388 leukemia.
Antitumor activity of four modified on amino sugar moiety derivatives of daunorubicin was compared with activity of two commercial preparations of the parental drug in tests against P 388 leukemia in mice. Tested analogs appeared to be similarly effective as the reference drugs, but two of them, DR-2 and DR-19, were found to be significantly less potent.


Trends in the use of surgical antibiotic prophylaxis in general pediatric surgery: Are we missing the mark for both stewardship and infection prevention?
The purpose of this study was to assess compliance with antimicrobial spectrum guidelines in the use of surgical antibiotic prophylaxis (SAP) in pediatric surgery. A retrospective cohort study of children undergoing elective clean-contaminated and clean surgical procedures with foreign body implantation using the Pediatric Health Information System database (10/2015-6/2018) was performed. Compliance rates with consensus guidelines surrounding appropriate spectrum of SAP coverage were calculated for each procedure. Undertreatment was defined as the use of SAP with inappropriately narrow coverage (or omission altogether), while overtreatment was defined as inappropriately broad coverage. Eight procedure groups including a total of 15,708 patients were included. Overall, 44% of cases received inappropriate prophylaxis, of which 58% were considered undertreatment and 42% overtreatment. Procedures with the highest rates of overtreatment included small bowel procedures (77%), colorectal procedures (29%), and hepatobiliary procedures (20%), while the highest rates of undertreatment were associated with placement of tunneled central venous catheters and ports (43%), hepatobiliary procedures (24%), and colorectal procedures (20%). Noncompliance with the recommended spectrum of coverage for surgical antibiotic prophylaxis is common in pediatric surgery, with both over and undertreatment being common themes. Improved compliance is needed to optimize both antibiotic stewardship and infection prevention. Treatment study. Level III.


Activating mutations of STAT3: Impact on human growth.
The signal transducer and activator of transcription (STAT) 3 is the most ubiquitous member of the STAT family and fulfills fundamental functions in immune and non-immune cells. Mutations in the STAT3 gene lead to different human diseases. Germline STAT3 activating or gain-of-function (GOF) mutations result in early-onset multiorgan autoimmunity, lymphoproliferation, recurrent infections and short stature. Since the first description of the disease, the clinical manifestations of STAT3 GOF mutations have expanded considerably. However, due to the complexity of immunological characteristics in patients carrying STAT3 GOF mutations, most of attention was focused on the immune alterations. This review summarizes current knowledge on STAT3 GOF mutations with special focus on the growth defects, since short stature is a predominant feature in this condition. Underlying mechanisms of STAT3 GOF disease are still poorly understood, and potential effects of STAT3 GOF mutations on the growth hormone signaling pathway are unclear. Functional studies of STAT3 GOF mutations and the broadening of clinical growth-related data in these patients are necessary to better delineate implications of STAT3 GOF mutations on growth.


Prevalence and associated psychosocial factors of increased hand hygiene practice during the influenza A/H1N1 pandemic: findings and prevention implications from a national survey in Taiwan.
To investigate increased hand hygiene practice in response to the pandemic influenza A/H1N1 (pH1N1) and its associated psychosocial factors in the Taiwanese general population. A national telephone survey using random digit dialing was conducted on October 28-30, 2009 in Taiwan, resulting in a final sample of 1079 participants aged 15 or older. Seventy-seven per cent reported that they increased hand hygiene practice during the pH1N1 epidemic. Multivariate logistic regression analysis showed that increased hand hygiene practice was associated with health beliefs that pH1N1 was more transmissible than avian influenza (OR = 1.42); that pH1N1 was slightly more severe in Taiwan compared with other countries (OR = 1.59); that handwashing was very effective in preventing pH1N1 (OR = 3.12), and that handwashing after contact with possibly pH1N1-contaminated objects/surfaces was not very difficult (OR = 2.14) or not difficult at all (OR = 2.49). These findings suggest that future campaigns to promote preventive health behaviour in the public should consider communicating evidence-based information concerning the effectiveness of the recommended preventive behaviour, comparing the emerging epidemic with prior local outbreaks, and not overplaying the seriousness of the disease with fear tactics.


miR-145-5p restrained cell growth, invasion, migration and tumorigenesis via modulating RHBDD1 in colorectal cancer via the EGFR-associated signaling pathway.
miR-145-5p has been reported to be downregulated and described functioning as a tumor suppressive gene in colorectal cancer (CRC), yet its detailed regulatory function and mechanism in malignant progression of the disease have not been thoroughly understood. In our study, miR-145-5p and rhomboid domain containing 1 (RHBDD1) in CRC tissues and cells were examined by qRT-PCR and western blot. MTT, colony formation, wound healing, Transwell invasion, and flow cytometry assays were performed to evaluate the malignant phenotypes of CRC cells. Xenograft tumor, qRT-PCR, and western blot assays were applied to validate the roles and mechanism of miR-145-5p in CRC in vivo. The interaction between miR-145-5p and RHBDD1 was investigated by luciferase reporter assay and western blot. The changes of the EGFR/Raf/MEK/ERK pathway were detected by western blot. We found miR-145-5p was lowly expressed and low miR-145-5p predicted poor prognosis in CRC, while RHBDD1 was greatly enhanced in CRC cells and tissues. RHBDD1 silencing resulted in inhibiting cell proliferative, invasive, and migratory potentials as well as elevating apoptotic ones in CRC cells. miR-145-5p was inversely related with RHBDD1 expression in CRC tissues. miR-145-5p was found to directly bind to RHBDD1 and restrained its expression in CRC cells. miR-145-5p overexpression repressed CRC cell proliferation, invasion, migration and induced apoptosis, and these effects were reversed by RHBDD1 upregulation. Moreover, in CRC xenograft tumor, its growth was impeded by miR-145-5p via suppressing RHBDD1. Furthermore, miR-145-5p inhibited the expression of EGFR, p-MEK1/2 and p-ERK1/2, in vitro and in vivo by targeting RHBDD1. In conclusion, our study revealed that miR-145-5p overexpression inhibited tumorigenesis in CRC by downregulating RHBDD1 via suppressing the EGFR-associated signaling pathway (EGFR/Raf/MEK/ERK cascades).


Graded expression of netrin-1 by specific neuronal subtypes in the adult mammalian striatum.
Netrins are a family of secreted proteins that function as axon guidance cues during neural development. High levels of netrin-1 expressed by the embryonic ganglionic eminence, the precursor of the adult striatum, direct axons that pioneer the internal capsule. Here we describe netrin-1 expression by neurons distributed throughout the striatum of the adult mouse. Differences were detected in the number and type of neurons expressing netrin-1 in different regions of the striatum. Most neurons in the ventral striatum, including projection neurons and cholinergic interneurons, express netrin-1. In contrast, netrin-1 expression is largely limited to cholinergic interneurons in the dorsal striatum, and the proportion of cholinergic interneurons that express netrin-1 decreases along rostral-caudal and ventral-dorsal axes. Regional differences in expression in the adult striatum suggest that netrin-1 not only influences the development of striatal circuitry but may also participate in the maintenance and plasticity of connections in the adult brain.


Anxiety sensitivity in patients with physically unexplained chronic back pain: a preliminary report.
It has been proposed that high anxiety sensitivity amplifies a number of fears and anxiety reactions. The purpose of this study was to examine whether anxiety sensitivity influences pain-related anxiety and associated cognitive and affective reactions in patients with physically unexplained chronic back pain. Seventy patients with chronic back pain without demonstrable organic pathology completed a battery of questionnaires prior to admission to a multidisciplinary treatment centre. Fourteen patients (20.0%) were classified as high, 44 (62.9%) as medium and 12 (17.1%) as low anxiety sensitive. Multivariate analysis of variance indicated that the high anxiety sensitive patients were more negatively affected by their experience with pain. Specifically, high anxiety sensitivity patients exhibited greater cognitive disruption and anxiety in response to pain, greater fear of negative consequences of pain, and greater negativity of affect than the other groups. Groups did not differ in the intensity of pain that they were experiencing. The proportion of high anxiety sensitive patients reporting current use of analgesic medication was, however, significantly greater than the medium and low anxiety sensitive patients. Correlational analyses indicated significant associations between anxiety sensitivity and pain-related cognitive/affective variables that were independent of pain severity. These results suggest that chronic back pain patients with high anxiety sensitivity, despite equal levels of pain severity, are more likely to be negatively affected by their pain experiences than those with medium and low anxiety sensitivity.


Decolonising money: learning from collective struggles for self-determination.
As a reflection of our politically engaged research, this paper addresses the multiple challenges of transforming money for the emergence of the Pluriverse, arguing that practical efforts of emancipation and autonomy need to dismantle the colonial nature of our current monetary system: the flip side of the colonial state. On the one hand, we look into Chiloé, a territory marked by long-term relations of colonialism, dependency and extraction, where the arrival of monetised forms of work in extractive industries has meant the destruction of former ways of inhabiting the territory. On the other, we explore the emergence of the Circles project, in Berlin, that aims at creating a basic income from the bottom-up, whereby people in different communities issue money equally and exchange with each other without the need for state cash. More than assuming that money in itself is 'bad', we suggest that a recovery of the social and ecological fabric of life could be done through local money systems, designed and managed by the communities themselves, delivered and redistributed as a basic income. Moving to a plural monetary system based on relations of care would lead to a recovery of history as a project of collective self-determination.


Development of a bifunctional sensor using haptenized acetylcholinesterase and application for the detection of cocaine and organophosphates.
We developed a dual piezoelectric/amperometric sensor for the detection of two unrelated analytes in one experiment that uses propidium to anchor acetylcholinesterases (AChE) at the surface. This mass-sensitive sensor does not only allow the examination of the interaction between AChE and the modified surface but also the detection of in situ inhibition of the surface-bound AChE. Here we describe the application of the propidium-based sensor in combination with a modified AChE. For this reason the cocaine derivative benzoylecgonine (BZE) was coupled via a 10A long hydrophilic linker - 1,8-diamino-3,4-dioxaoctane - to carboxylic groups of the AChE after EDC/NHS activation. Thus the modified AChE (BZE-AChE) possesses an additional recognition element besides the inhibitor binding site. After the deposition of BZE-AChE on the sensor surface the binding of an anti-BZE-antibody to the BZE-AChE can be monitored. This makes it possible to determine two analytes - cocaine and organophosphate - in one experiment by measuring antibody binding and decrease in enzymatic activity, respectively. Furthermore it was also shown that other cocaine-binding enzymes, e.g., butyrylcholinesterase, can bind to the modified BZE-AChE. The competitive immunoassay allowed the detection of cocaine with a dynamic range from 10(-9) to 10(-7)M. The organophosphate chlorpyrifos-oxon could be detected in concentrations from 10(-6) down to 10(-8)M after 20 min of injection time (equals to 500 microL sample volume.


Antibiotic treatment during post-natal reverses behavioural and molecular alterations in experimental meningitis survivor rat model.
The present study was aimed to examine the behavioural and molecular alterations in experimental meningitis survivor rat model. On postnatal day (PND)-2, animals were assigned to different groups: (i) Control (Ctrl), (ii) Positive Control [PCtrl: gavaged with Luria-Bertani (LB) broth on PND-2 and received antibiotics treatment (AbT) from PND-5 to 11], (iii) Cronobacter sakazakii (CS: received single dose of live bacterial culture on PND-2) infected. Later, a subset of CS group received antibiotics treatment (AbT) from PND-5 to 11 and assigned as group (iv) (CS + AbT/ survivor). On PND-35, animals were subjected to behavioural tasks [viz., elevated plus maze (EPM) test and step-through inhibitory retention], and sacrificed for molecular analyses. We found that CS infection induces anxiety-like behaviour, impaired short/long-term memory and differentially altered the expression of brain-derived neurotrophic factor (BDNF) splice variants (III, IV and VI), decreased expression of BDNF, Src family tyrosine kinase (FYN), focal adhesion kinase (FAK) and nerve growth factor (NGF). The observed behavioural phenotype and expression pattern of candidate genes fit in the correlation. In addition, NGF expression was reduced in dentate gyrus (DG) and CA1 regions of hippocampus. Notably, antibiotic treatment reduced the anxiety-like behaviour, improved step-through inhibitory retention and suppressed infection induced reduction in BDNF, FYN, FAK and NGF expressions in survivors, however, not comparable to the control group. Overall, our experimental meningitis survivor model demonstrate that antibiotic treatment minimize the C. sakazakii infection induced effect on behaviour and signaling molecules involving in neuronal development, survival, and synaptic plasticity, but the consequences are long-term.


Evaluation of the murine metrial gland for immunological function.
The metrial gland (MG) is a transient uterine structure associated with rodent pregnancy. The gland is a complex structure consisting of stromal and vascular elements, as well as a population of histologically distinctive, large, granulated metrial gland (GMG) cells. The functions of the MG and of the GMG cells, as well as their relationship to the success of pregnancy, are unknown. Based upon morphological and morphometric studies it has been proposed that the MG might be involved in the immunology of pregnancy and that GMG cells could be immunocompetent. Explant cultures of MG have therefore been evaluated for immunological function. Lytic activity against the NK sensitive target cell line YAC and mitogen responsiveness could not be detected. MG tissue and medium conditioned by overnight culture of MG tissue (MG-CM) suppressed the response of murine spleen cells to Con A. MG-CM also reduced the lytic activity of splenic NK cells against YAC target cells. However, uptake of [3H]thymidine was elevated when YAC cells were cultured in MG-CM. The response of embryonic and uterine cells to growth in MG-CM was complex. MG-CM had little effect on isotope incorporation by decidual cells recovered at 6.5 days or by embryonic cells recovered from 12.5 day embryos. However, thymidine incorporation was less in MG-CM than in control medium for 12.5 day placental cells, 6.5 day embryonic sac, 6.5 day ectoplacental cone and 3.5 day blastocysts. Cytotoxicity and cytostasis accounted for reduced uptake of isotope in cultures of 3.5 day blastocysts and 6.5 day embryonic tissues. Loss of viability could not be detected in any other assays. Both YAC cells and unstimulated splenocytes showed altered morphology and improved viability when cultured in MG-CM. This study suggests that the only immunological role the MG might have during normal pregnancy is that of non-specific intra-uterine suppression. Alternatively, differential regulation of cell proliferation might be a function of the MG, within the pregnant uterus. The latter mechanism could also account for the apparent observation of non-specific immunosuppression.


[Rhinoplasty of unilateral cleft lip].
To investigate the technique for unilateral cleft lip nasal deformities. Through the traditional columella margin incision, the alar cartilage and the lateral nasal cartilage were exposed. After the mucosa between the two cartilages was divided, a mucosa-cartilage flap was developed and anchored, moving the lateral crus upwardly and medially, correcting the nasal deformity. 52 cases of primary nasal deformities and 18 cases of secondary nasal deformities were corrected with this technique. Satisfactory results were achieved. This technique is recommendable, which is more likely to restore the physiological characters of the nose than the conventional technique.


An Audit of Tracheostomy in Traumatic Brain Injury.
The timing of tracheostomy in traumatic brain injury is controversial. The benefits of early tracheostomy are early weaning from ventilation, and reduction in pneumonia. But some studies demonstrated increase in intracranial pressure during tracheostomy. The aims of the audit are to analyse the timing, benefits, complications, and the results of tracheostomy in patients with traumatic brain injury in the hospital in the period of 2012-2021. The number of patients was 34. The maximum number of tracheostomies(24) were between 6th to 14th days of admission. The complications were: worsening of Glasgow coma scale score - 3 (in the early group), bleeding - 2, subglottic stenosis-1, tracheocutaneous fistula-1. The main benefits obtained form tracheostomy were the easiness of weaning and tracheobronchial toilet. Twelve patients had pneumonia. Nine patients survived out of twelve. Six patients had acute respiratory distress syndrome. Five of them succumbed. The weaning time corresponded to the severity of injury and pulmonary status. The mortality according to the timing of tracheostomy were: 1/6(16.67%) in the group of first week, 9/19(47%) in the group of second week, and 3/8(37.5%) in the group of the third and fourth week. The mortality was less in the group of first week. The timing of tracheostomy in traumatic brain injury should be at the earliest after the control of raised intracranial tension. There was reversible worsening of Glasgow coma scale score for 2 points in 3 cases after early tracheostomy. Mortality was less in the group of early tracheostomy.


Clearance of Mycoplasma genitalium Infection With Moxifloxacin in the Presence of Quinolone Resistance-Associated Mutations.
We present 2 cases of Mycoplasma genitalium infection that were successfully treated with moxifloxacin despite the presence of quinolone resistance-associated mutations in these strains.


Air sampling procedure for evaluation of viral excretion level by vaccinated pigs infected with Aujeszky's disease (pseudorabies) virus.
Five groups of eight fattening pigs were vaccinated and then infected with Aujeszky's disease virus. Viral excretion was evaluated by two means: deep nasal swabbing and air sampling. It appeared that infectious airborne virus could be recovered from day 1 to day 6 after infection in the isolated units where control animals were raised. In vaccinated animals, airborne particles were also detected but the amount and duration varied in relation to their immune status at the day of virulent challenge: viral excretion was significantly lower in pigs presenting a high antibody level (1/16 to 1/64) just before infection. Results obtained with nasal swabs and with air samples were closely related. Despite its low sensitivity, the air sampling procedure could be considered as an efficient tool for reflecting infectious viral pressure in a confined atmosphere.


Head-to-Tail Polymerization in the Assembly of Biomolecular Condensates.
Clustering of macromolecules is a fundamental cellular device underlying diverse biological processes that require high-avidity binding to effectors and substrates. Often, this involves a transition between diffuse and locally concentrated molecules akin to biophysical phase separation observable in vitro. One simple mechanistic paradigm underlying physiologically relevant phase transitions in cells is the reversible head-to-tail polymerization of hub proteins into filaments that are cross-linked by dimerization into dynamic three-dimensional molecular condensates. While many diverse folds and motifs can mediate dimerization, only two structurally distinct domains have been discovered so far to undergo head-to-tail polymerization, though these are widespread among all living kingdoms.


Influencing Perceptions of Harm of Waterpipe Tobacco Smoking Among One Member of Couples Who Use Waterpipe.
Waterpipe tobacco smoking (WTS) often occurs socially, increasing health risks for the smoker and others through secondhand smoke effects. While messages on WTS harms enhance perceived risks for self, whether these messages elevate perceived risks for others, such as one's romantic partner who engages in WTS, is unclear. We tested this idea by surveying one member of dual-smoking couples who engages in WTS. As part of an online study, we enrolled adults ages 18-30 who engaged in WTS and were in a committed relationship of at least 6 months whose partner engaged in WTS. Participants were randomized to a control arm or to one of two arms consisting of watching a brief video on health harms or overcoming myths about WTS, respectively. Outcomes were perceived harms and measures of desire and probability of quitting for self and partner. Participants (N = 238) who watched either video, compared with participants who did not watch a video, reported greater perceived health risks for self and partner and that their own WTS harmed their partner. Participants who watched either video reported a greater desire to quit for themselves, perceived that their partner had a greater desire to quit, and reported a higher likelihood of quitting together in the next 6 months. Brief videos containing risk-based messaging increase young adult waterpipe tobacco smokers' perceived harms and desire to quit for self and partner. This can be a useful strategy to motivate cessation in couples who engage in WTS. This study shows for the first time that at least among one member of dual-smoking couples who engages in WTS, brief videos on harms of WTS influences perceived harms and motivation to quit for the self and one's partner. This can be a useful strategy to promote cessation.


Febuxostat attenuates aluminum chloride-induced hepatorenal injury in rats with the impact of Nrf2, Crat, Car3, and MNK-mediated apoptosis.
Aluminum (Al) is a ubiquitous xenobiotic with known toxicity for both humans and animals. Our study was conducted to investigate the protective role of febuxostat (Feb) against aluminum chloride (AlCl3)-induced hepatorenal injury in rats. Hepatorenal injury was induced by oral administration of AlCl3 (40 mg/kg b.w.), for 2 months. Twenty-four male Sprague-Dawley rats were randomly allocated into four groups (six rats/group). The first group received the vehicle thought the experiment. The second group was considered as a control positive group. The third and fourth groups received oral treatment of Feb (10 mg/kg.b.w.) and (15 mg/kg.b.w.), respectively with AlCl3, concurrently for 2 months. Twenty-four hours, after the last treatment, serum biochemical, molecular, histopathology, and immunohistochemical studies were evaluated. Our findings showed that rats intoxicated with Alcl3 had disturbed biochemical picture. In addition, intoxication with AlCl3 increased oxidative stress and apoptosis, as demonstrated by an increase in malodialdeyde (MDA), carnitine o-acetyltransferase (Crat), and carbonic anhydrase (Car3) with a decrease in glutathione (GSH), MAP kinase-interacting serine/threonine kinase (MNK) and nuclear factor-erythroid 2-related factor 2 (Nrf2) mRNA expression. Furthermore, the levels of tumor necrosis factor-alpha (TNF-α) and the levels of caspase-3 were elevated with sever hepatic and renal pathological changes. Conversely, Feb (15 mg/kg.b.w.) could improve the serum biochemical indices and repressed MDA, Crat, and Car3 levels, whereas it increased GSH, MNK, and Nrf2 levels. Feb inhibited the apoptotic effect of AlCl3 in the liver and kidney by decreasing caspase-3 and TNF-α expression. The protective effect of Feb against AlCl3 toxicity was confirmed by histopathological findings. Moreover, molecular docking studies supported the anti-inflammatory effect of Feb due to its significant binding interactions with cyclooxygenase-1 (COX-1), NF-kappa-B-inducing kinase (NIK), and mitogen-activated protein kinases-p38 (MAPK-p38). The findings suggest that Feb system Feb can avert Alcl3-induced hepatotoxicity and nephrotoxicity by enhancing the antioxidant defense system, and inhibiting the inflammatory cascade and apoptosis.


Soxhlet-assisted matrix solid phase dispersion to extract flavonoids from rape (Brassica campestris) bee pollen.
Soxhlet-assisted matrix solid phase dispersion (SA-MSPD) method was developed to extract flavonoids from rape (Brassica campestris) bee pollen. Extraction parameters including the extraction solvent, the extraction time, and the solid support conditions were investigated and optimized. The best extraction yields were obtained using ethanol as the extraction solvent, silica gel as the solid support with 1:2 samples to solid support ratio, and the extraction time of one hour. Comparing with the conventional solvent extraction and Soxhlet method, our results show that SA-MSPD method is a more effective technique with clean-up ability. In the test of six different samples of rape bee pollen, the extracted content of flavonoids was close to 10mg/g. The present work provided a simple and effective method for extracting flavonoids from rape bee pollen, and it could be applied in the studies of other kinds of bee pollen.


Utility of saturation biopsy to predict insignificant cancer at radical prostatectomy.
To determine whether potential candidates for watchful waiting have undersampling of more substantial cancer. A total of 103 men were studied, who were predicted to have insignificant cancer in their radical prostatectomy (RP) specimen. All had limited cancer on routine needle biopsy (no core with more than 50% involvement; Gleason score less than 7, and fewer than 3 cores involved) with a serum prostate-specific antigen density of 0.15 or less. Insignificant tumor at RP was considered organ-confined tumor, no Gleason pattern 4 or 5, and a tumor volume of less than 0.5 cm3. Saturation biopsy (average 44 cores) and an alternate biopsy saturation scheme with one half the number of cores using an 18-gauge Biopty gun was performed in the pathology laboratory on totally embedded and serially sectioned RP specimens. Of the tumors, 97% were organ confined. The RP Gleason score was less than 7 in 84% of the cases. The RP tumor volume was 0.01 to 2.39 cm3 (median 0.14). Of the cancer specimens, 71% were insignificant and 29% had been incorrectly classified before surgery using standard biopsy schemes. Using the full saturation biopsy scheme, if we predicted significant cancer, the probability of having insignificant cancer was only 11.5% (false-positive rate). If the model predicted insignificant cancer, the probability of significant cancer was also only 11.5% (false-negative rate; sensitivity 71.9% and specificity 95.8%). Using the alternate biopsy sampling scheme, the false-positive rate was 8% and the false-negative rate was 11.4% (sensitivity 71.9% and specificity 97.1%). Saturation biopsy provides accurate predictability of prostate tumor volume and grade to select suitable candidates for watchful waiting therapy.


Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.
Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value < 5 × 10-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits.


Mucocele-like tumor associated with ductal carcinoma in situ diagnosed as mucinous carcinoma by fine-needle aspiration cytology: report of a case.
Mucocele-like tumors (MLTs) of the breast are rare, with only 11 cases reported from Japan and 35 cases from other countries. MLTs of the breast were first described by Rosen in 1986. They are believed to be related to atypical ductal hyperplasia, ductal carcinoma, or mucinous carcinoma. It is difficult to diagnose this tumor preoperatively, and especially difficult to differentiate between benign and malignant forms. We report a case of MLT associated with ductal carcinoma in situ, which was initially diagnosed as fibroadenoma by mammography and ultrasonography, and as mucinous carcinoma by fine-needle aspiration cytology. We discuss the characteristic findings of imaging and the appropriate clinical treatment of this tumor. The characteristic image first signals the possibility of this tumor, following which the diagnosis can be confirmed by pathological examination of a fully excised tumor specimen. Breast-conserving surgery is recommended because of the low risk of high-grade malignancy, even when malignancy is confirmed, and lymph node dissection may be avoided.


[Phlebotomines collected in remaining forests and wild animal shelters from the zoological garden of the Maringa urban area, southern Brazil. Preliminary study].
The present study was undertaken after the detection of one case of cutaneous leishmaniasis with presumed infection in one of the three remaining wooded areas in the urban area of the city of Maringá, Southern Brazil; also in view of the lack of knowledge about sand flies and their behavior. From June to September, 1995, sand flies were caught with Falcão traps during the night in the remaining wooded areas (Parque do Ingá, Bosque Dois and Horto Florestal). A total of 2,907 sand flies were caught in Parque do Ingá; 1,723 of them were aught in forest traps and 1,184 in wild animal shelter traps at the zoo. The results show that Lutzomyia whitmani is better adapted to the three areas under study and that it frequently occurs in wild animal shelters within the urban perimeter of Maringá.


Total Hip Arthroplasty Functional Outcomes Are Independent of Acetabular Component Orientation When a Polyethylene Liner Is Used.
This study evaluated patient-reported outcomes in patients undergoing primary total hip arthroplasty with a polyethylene liner to determine the influence of cup orientation and other variables on patient-reported outcomes. A total of 477 cases were prospectively monitored through average 4.7 years follow-up. Cup position was measured on pelvis radiographs. Patients completed the Western Ontario and McMaster Universities Osteoarthritis Index and Short Form 12 Health Survey questionnaires. Average cup abduction was 43.1° ± 7.5° and anteversion was 13.3° ± 7.5°. Three hundred cups were within the target zone. All outcomes' improvement from baseline and cup position was not an independent risk factor for the Western Ontario and McMaster Universities Osteoarthritis Index or Short Form 12 Health Survey improvement. Accurate cup orientation may not be critical to maximizing patient-perceived outcomes if the combined anteversion is within a normal range, the hip joint is properly balanced, and a polyethylene liner is coupled with a metal or ceramic femoral head.


Replacement of femoral head endoprosthesis with total hip prosthesis. A report of five cases with problems of management.
Five cases who had endoprosthesis implanted for medial fracture of the neck of the femur are reported. All of them developed late complications that required replacements of endoprosthesis with total hip prosthesis. Complications included wearing of both joint cartilage and subchondral bone of the acetabulum, osteoporosis of the proximal end of the femur and fracture of the femur and the level of the endoprosthesis. Several problems of surgical management ensued. This experience strengthens the author's opinion that other forms of treatment--reduction in traction and nailing or total hip prosthesis--should be tried first also in particular cases of chronologically aged, but physically healthy patients with medial fractures of the neck of the femur.


The role of Ser54 in the antinociceptive activity of BmK9, a neurotoxin from the scorpion Buthus martensii Karsch.
Residue 54 has been shown to be important for bioactivity in several toxins. However, its role in the antinociceptive activity of toxins has not been evaluated yet. In this study, site-directed mutagenesis and mouse acetic acid writhing test were used to investigate the role of Ser54 in the antinociceptive activity of BmK9 neurotoxin from the Buthus martensii Karsch scorpion. Detailed mutagenesis analysis revealed that substitution of Ser54 by various polar amino acids produced no significant change in the antinociceptive activity, while all substitutions of nonpolar amino acid for Ser54 led to a significant loss of antinociceptive activity. Following the conformational analysis, it was suggested that Ser54 in BmK9 plays a functional role in the antinociceptive activity, the residue exerts its effect by means of a side-chain hydrogen bond.


[Demonstration of 3 functional domains responsible for a kinase activity in VirA, a transmembrane sensory protein encoded by the Ti plasmid of Agrobacterium tumefaciens].
High-level expression of chimeric virA genes were obtained by replacing the first codons of virA with the first codons of trpE. The fusion proteins encoded by these constructs were partially purified and one of them exhibited autokinase activity. Therefore, protein phosphorylation may be an important feature of VirA function. This allowed us to define the existence of three functional domains inside VirA.


Carotico-cavernous fistula: An educational case.
We present a case of direct carotico-cavernous fistula (CCF) and its successful treatment. A 55-year-old male presented with left eye discomfort, diplopia and pulsatile tinnitus. He had a recent history of head injury. Examination showed proptosis, chemosis, orbital bruit, and abducens nerve palsy. Digital subtraction angiography confirmed CCF, which was managed endovascularly. The patient recovered fully after treatment. CCF has a variety of presenting clinical signs, imaging manifestations, and treatment options available. CCF is a rare and dangerous neurological disorder that should be promptly diagnosed and treated.


An advanced course in long term care for geriatric medicine fellows.
Long term care deserves focused attention within a geriatric medicine fellowship curriculum to ensure that graduates are prepared not only for clinical care but also for the leadership, administrative, educational, quality improvement, and health policy aspects of their future roles. This report describes the curriculum development and program evaluation of an advanced course in long term care for geriatric medicine fellows and other graduate/post-graduate health professionals at Duke University. Course evaluation had 4 goals: (1) to determine how well the learning objectives were met; (2) to evaluate individual components of the course to improve subsequent offerings; (3) to determine whether additional topics needed to be added; and (4) to evaluate the effectiveness of the discussion forum component of the course. Learner self-efficacy improved within all competency areas but especially those of practice-based learning and system-based practice. Evaluation results led to curriculum revision that has maintained course relevance and sustained it within the larger geriatrics fellowship curriculum. Components of this course can be easily adapted to other curricular settings for fellows and residents.


Variable expression of linguistic laws in ape gesture: a case study from chimpanzee sexual solicitation.
Two language laws have been identified as consistent patterns shaping animal behaviour, both acting on the organizational level of communicative systems. Zipf's law of brevity describes a negative relationship between behavioural length and frequency. Menzerath's law defines a negative correlation between the number of behaviours in a sequence and average length of the behaviour composing it. Both laws have been linked with the information-theoretic principle of compression, which tends to minimize code length. We investigated their presence in a case study of male chimpanzee sexual solicitation gesture. We failed to find evidence supporting Zipf's law of brevity, but solicitation gestures followed Menzerath's law: longer sequences had shorter average gesture duration. Our results extend previous findings suggesting gesturing may be limited by individual energetic constraints. However, such patterns may only emerge in sufficiently large datasets. Chimpanzee gestural repertoires do not appear to manifest a consistent principle of compression previously described in many other close-range systems of communication. Importantly, the same signallers and signals were previously shown to adhere to these laws in subsets of the repertoire when used in play; highlighting that, in addition to selection on the signal repertoire, ape gestural expression appears shaped by factors in the immediate socio-ecological context.


Risk of RBC alloimmunization in multiple myeloma patients treated by Daratumumab.
Daratumumab (DARA) is a human monoclonal antibody for the treatment of multiple myeloma (MM). DARA binds to CD38 on RBCs and interferes with detection of RBC alloantibodies. The objective of this study was to evaluate the risk of RBC alloimmunization in MM patients treated with DARA. A retrospective study of the complete serological profile and transfusion history of 45 MM patients received transfusion and treated with DARA from July 2015 to December 2018 was undertaken. All cases with positive Ab screens were treated with DTT to identify RBC alloantibodies. RBC transfusion history was monitored between the first DARA dose to the last or extending to the first negative Ab screen after the last DARA dose if the Ab screen was ever positive. Forty-six MM patients received transfusion but not DARA were studied as control group. Totally 184 Ab screens were done on 45 patients transfused with ABO-Rh compatible RBCs, phenotypically matched units or both. None of them showed detectable alloantibodies after DTT treatment. The duration of Ab screening positivity varied markedly, ranging from 25 days to 5 months after the last dose. Two of 46 patients in the control group had preexisting alloantibodies but no new alloantibodies were detected during study period. Our results indicate that the risk of forming new RBC alloantibodies after transfusion in MM patients treated with current regimens is very low and no DARA-associated difference in the alloimmunization risk. No significant difference in alloimmunization is detected between ABO-Rh compatible and phenotypically matched transfusion.


Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.
A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained.


Nonmyeloablative allogeneic bone marrow transplantation for orbital granulocytic sarcoma associated with t(8;21)(q22;q22) in acute myeloid leukemia.
We report a nonmyeloablative allogeneic bone marrow transplant (allo-BMT) from an HLA-matched unrelated donor in a case of acute myeloid leukemia (AML), M2 with t(8;21)(q22;q22) and the presence of orbital granulocytic sarcoma (GS), who had residual tumor after conventional chemotherapy. The course of BMT was well tolerated, with no major procedure-related toxicity. The residual orbital GS regressed completely 4 months after BMT. She is currently 19 months post BMT, disease-free. To our knowledge, this is the first reported pediatric patient with AML, GS and t(8;21)(q22;q22) who received a nonmyeloablative allo-BMT.


Conformational properties of two exopolysaccharides produced by Inquilinus limosus, a cystic fibrosis lung pathogen.
Inquilinus limosus is a multi-resistant bacterium found in the respiratory tract of patients with cystic fibrosis. This bacterium produces two unique fully pyruvylated exopolysaccharides in similar quantities: an α-(1→2)-linked mannan and a β-(1→3)-linked glucan. We employed molecular modelling methods to probe the characteristic conformations and dynamics of these polysaccharides, with corroboration from potentiometric titrations and circular dichroism experiments. Our calculations reveal different structural motifs for the mannan and glucan polysaccharides: the glucan forms primarily right-handed helices with a wide range of extensions, while the mannan forms only left-handed helices. This finding is supported by our circular dichroism experiments. Our calculations also show that the (1→3)-β-d-Glcp linkage is more dynamically flexible than the (1→2)-α-d-Manp: the glucan characteristically forms a range of wide helices with large central cavities. In contrast, the mannan forms rigid regular 'bottlebrush' helices with a minimal central cavity. The widely different character of these two polymers suggests a possible differentiation of biological roles.


Evaluation of insulin resistant diabetes mellitus in Alström syndrome: a long-term prospective follow-up of three siblings.
Alström syndrome is a rare cause of diabetes mellitus. We studied two generations of a Turkish family in whom four members were affected by Alström syndrome. The natural course of the syndrome in three sisters was followed for 13 yr. The three sisters had short stature and truncal obesity, and developed complete blindness due to retinitis pigmentosa at 10, 5 and 13 yr of age. Two had sensorineural hearing loss and mild mental retardation, while the other developed diabetic ketoacidosis (DKA) at 14 yr and was treated with insulin from onset of diabetes. In the second case, diagnosis of diabetes was made by an OGTT at age 20 yr, and controlled with diet alone for 11 yr, then with a sulphonylurea for 2.5 yr, then with insulin. The third case developed acute hyperglycaemia at 20 yr, and required insulin from onset. Moreover, transitional features of impaired carbohydrate and fat metabolism (severe hyperinsulinaemia and insulin resistance progressing to islet beta cell failure, and hypertriglyceridaemia with fatty liver) were demonstrated, in accord with the literature. Previously unreported findings characteristic of nephro-uropathy with early-onset hypertension were also detected, and included in all cases proteinuria, glomerulopathy, and abnormal locations of the kidneys, narrowed uretero-renal junctions and dilated ureters.


Coordination of neuronal activity by gap junctions in the developing neocortex.
During embryonic development, gap junctions link cells into functional communication compartments characterized by a common development fate. Increasing evidence for gap junctions between immature neurons suggest that similar mechanisms may also be at work in the developing vertebrate brain, where gap junction-coupled neuronal assemblies often precede synaptically-linked functional networks. Recent experiments in the developing mammalian neocortex demonstrated the presence of gap-junction mediated second messenger waves, similar to those in non-neuronal cells. The primary function of neuronal gap junctions, therefore, might be to coordinate biochemical activity, rather than to act as purely electrical synapses. Thus, gap junctions may serve to amplify neuronal activity produced by weak synaptic stimulation.


Malakoplakia of testis.
Malakoplakia of the testicle was first reported in 1958. Since then approximately 25 cases have been reported. We add another case.


Approaches to Disease Modification for Parkinson's Disease: Clinical Trials and Lessons Learned.
Despite many clinical trials over the last three decades, the goal of demonstrating that a treatment slows the progression of Parkinson's disease (PD) remains elusive. Research advances have shed new insight into cellular pathways contributing to PD pathogenesis and offer increasingly compelling therapeutic targets. Here we review recent and ongoing clinical trials employing novel strategies toward disease modification, including those targeting alpha-synuclein and those repurposing drugs approved for other indications. Active and passive immunotherapy approaches are being studied with the goal to modify the spread of alpha-synuclein pathology in the brain. Classes of currently available drugs that have been proposed to have potential disease-modifying effects for PD include calcium channel blockers, antioxidants, anti-inflammatory agents, iron-chelating agents, glucagon-like peptide 1 agonists, and cAbl tyrosine kinase inhibitors. The mechanistic diversity of these treatments offers hope, but to date, results from these trials have been disappointing. Nevertheless, they provide useful lessons in guiding future therapeutic development.


Oral bioavailability and pharmacokinetics of baquiloprim in dwarf goats.
The pharmacokinetics of baquiloprim at a dose of 8 mg kg-1 bodyweight were determined after its intravenous and intra-ruminal administration to seven healthy female dwarf goats. After intravenous injection, the plasma elimination curve showed a rapid distribution phase (mean [SD] t1/2 alpha 0.89 [0.4] hours). The mean volume of distribution at steady-state (Vdss) was 14.1 (2.7) litres kg-1 bodyweight. The mean elimination half-life (t1/2 beta) was 14.0 (2.3) hours. After intra-ruminal administration its maximum concentration in plasma (Cmax) was 0.09 (0.01 microgram ml-1 and this maximum was not reached until approximately 35 hours after administration. The systemic oral bioavailability, calculated up to 48 hours after dosing, was 33.7 (7.1) per cent. Owing to a prolonged absorption phase, the data from only four of the goats fitted reasonably to a compartmental model.


Iron gets in the way.
Accumulation of iron with age may inhibit the benefits of hormone replacement therapy on cardiovascular disease in late postmenopause.


Multiple arterial variations in the upper limb: description and clinical relevance.
Although arterial variations in the upper limb are usually found during anatomical dissections and clinical practice, multiple arterial variations associated with nervous variations along the limb is rare and clinically relevant. This paper described a combined anatomical variation involving the neurovasculature in the upper limb. A left upper limb dissection of a male cadaver with approximately 50-60 years of age, fixed in 10% formalin, was performed. During the dissection was observed, the brachial artery ending in the middle third of the arm in three branches: a nutritional branch for the biceps brachii muscle, a "lateral brachial artery" and a "medial brachial artery", which became, after unusual paths crossing over the cubital fossa, the ulnar artery and the radial artery, respectively. Radial and ulnar artery demonstrated several unusual anastomotic branches, respectively, and an anastomotic arch around the biceps brachii muscle tendon. Such combined anatomical variation is unique and relevant for clinical and surgical practice.


Predictors of Mortality among Tuberculosis/HIV-Coinfected Persons in Southwest Ethiopia: A Case-Control Study.
Tuberculosis (TB) remains the most common cause of death in people living with HIV/AIDS. The aim of the present study was to identify predictors of mortality in TB/HIV-coinfected patients. We conducted an unmatched case-control study among a cohort of TB/HIV-coinfected adults who were on antiretroviral therapy (ART). Cases comprised 69 TB/HIV-coinfected patients who died during this period. For each case, we selected 3 (207) TB/HIV-coinfected patients who were alive during the end of the follow-up period. Male sex (odds ratio [OR] = 2.04, 95% confidence interval [CI]: 1.04-4.02), being bedridden at enrollment (OR = 2.84, 95% CI: 1.17-6.89), and cough of more than 2 weeks during initiation of ART (OR = 4.75 95% CI: 2.14-10.56) were the best predictors of mortality among TB/HIV-coinfected patients. Mortality among TB/HIV-coinfected patients accounted for a considerable number of deaths among the cohort. Patients with cough at ART initiation and with poor functional status should be strictly followed to reduce death.


Blood-feeding and nectar-feeding in adult tabanidae (Diptera).
Nectar-feeding frequently occurs in male and female tabanids. 53% of the 7,002 females and 69% of the 2,436 males reacted positively to cold anthrone. Although there are seasonal fluctuations in rates of blood and nectar-feeding, the acquisition of sugars may be essential for tabanid survival during the summer. Differences in blood-feeding rates among the species may indicate different blood-sucking habits.