A novel computer-controlled conditioned avoidance apparatus for rats.
Described and evaluated here is a newly designed apparatus for the assessment of conditioned avoidance response (CAR) performance in rats. The system is computer-assisted using a design and system control development package based on the virtual instrument concept (LabView). The program, which allows for significant flexibility, greatly facilitated and simplified the process of timing and data acquisition. The apparatus was found effective and appropriately designed for CAR performance training, as well as for a reliable assessment of the effects of antipsychotic and potentially antipsychotic compounds on CAR in rats. The design presents a new, effective, and inexpensive option for laboratories involved in animal behavioral research.


Association of outborn versus inborn birth status on the in-hospital outcomes of neonates treated with therapeutic hypothermia: A propensity score-weighted cohort study.
To compare the risk of in-hospital mortality and morbidity between outborn and inborn neonates treated with whole body hypothermia. The association of outborn birth status with in-hospital mortality and morbidity, prior to NICU discharge or transfer, was assessed in a large historical cohort of neonates who had therapeutic hypothermia initiated on the day of birth. The cohort was restricted to neonates born at ≥35 weeks gestational age from 2007 to 2018. Since the sample was non-random, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalance in baseline maternal and neonatal characteristics between outborn and inborn neonates. Cox proportional hazards regression was used to assess the association between outborn status and in-hospital mortality. There were 4447 neonates included in the study (2463 outborn). Outborn status was not significantly associated with an increased risk of in-hospital mortality in the unadjusted cohort (HR = 1.17, 95% CI 0.97-1.42, p = 0.10) or IPW cohort (HR = 1.09, 95% CI 0.95-1.26, p = 0.22). However, in the IPW cohort, outborn neonates were significantly more likely to have seizures (28% vs 24%, p = 0.006), anticonvulsant exposure (46% vs 41%, p = 0.002), and gastrostomy tube placement (5.8% vs 3.8%, p = 0.009) during their newborn hospitalization. Outborn status was not significantly associated with increased in-hospital mortality among neonates treated with whole body hypothermia. However, outborn neonates were more likely to have seizures, receive anticonvulsant treatment, and undergo gastrostomy tube placement. Further study is needed to better understand the etiologies of these outcome disparities and potential implications for long-term neurodevelopmental outcomes.


Nanosecond nonlinear Čerenkov conical beams generation by intracavity sum frequency mixing in KTiOAsO4 crystal.
Nanosecond Čerenkov-type conical beam at 628 nm is obtained by intracavity sum frequency mixing (SFM) of 1064 and 1534 nm in KTiOAsO(4) (KTA) crystal. The 1534 nm signal generated by the KTA optical parametric oscillation (OPO), respectively, interacts with the orthogonally polarized 1064 nm radiations by the nonlinear Čerenkov SFM, emitting two red rings with cone angles of 11.4° and 16.0°, respectively. Multidomain structure observed in the KTA crystal can account for the corresponding phenomenon. The KTA crystal simultaneously serves as OPO medium and Čerenkov radiation emitter in this experiment, indicating that it is a promising multifunctional nonlinear crystal material. Furthermore, the naturally grown crystal combined with intracavity Čerenkov-type configuration will provide a simple and compact approach, opening a door for the wide application of nonlinear Čerenkov radiation sources due to its cost-effectiveness.


Leadless pacemaker implantation quality: importance of the operator's experience.
Leadless cardiac pacemaker (PM) implantation differs from conventional PM implantation. While the procedure has been considered safe, recent real-world data raised concerns about the learning curve of new operators and their implantation quality. The goal of this study was to investigate the influence of the first operator's experience on leadless PM implantation quality and procedural efficiency. We performed a bicentric analysis of all Micra TPS™ implantations in two large tertiary referral hospitals. We assessed both leadless PM implantation quality based on the absence of complications (requiring intervention or prolonged hospitalization), good electrical performance (pacing threshold ≤ 1.5 V/0.24 ms, R-wave amplitude > 5 mV), and acceptable fluoroscopy duration (<10 min) as well as procedural efficiency in relation to the operator's experience. Univariate and multivariate logistic regression analyses were performed to identify predictors for implantation quality and procedural efficiency. Leadless PM implantation was successful in 106/111 cases (95.5%). Three patients (2.7%) experienced acute complications (one cardiac tamponade, one femoral bleeding, one posture-related PM exit block). Multivariate analysis showed that implantation quality of more experienced first operators was higher [odds ratio 1.09 (95% confidence interval 1.00-1.19), P = 0.05]. Procedural efficiency increased with operator experience as evidenced by an inverse correlation of procedure time, time to the first deployment, fluoroscopy time, and the number of procedures performed (all P < 0.05). The operator's learning curve is a critical factor for leadless PM implantation quality and procedural efficiency.


Genetic heterogeneity of group A rotaviruses: a review of the evolutionary dynamics and implication on vaccination.
Human rotavirus remains a major etiology of acute gastroenteritis among under 5-year children worldwide despite the availability of oral vaccines. The genetic instability of rotavirus and the ability to form different combinations from the different G- and P-types reshapes the antigenic landscape of emerging strains which often display limited or no antigen identities with the vaccine strain. As evidence also suggests, the selection of the antigenically distinct novel or rare strains and their successful spread in the human population has raised concerns regarding undermining the effectiveness of vaccination programs. We review aspects related to current knowledge about genetic and antigenic heterogeneity of rotavirus, the mechanism of genetic diversity and evolution, and the implication of genetic change on vaccination. Genetic changes in the segmented genome of rotavirus can alter the antigenic landscape on the virion capsid and further promote viral fitness in a fully vaccinated population. Against this background, the potential risk of the appearance of new rotavirus strains over the long term would be better predicted by a continued and increased close monitoring of the variants across the globe to identify any change associated with disease dynamics.


Assessment of mumps-containing vaccine effectiveness during an outbreak: Importance to introduce the 2-dose schedule for China.
China has used 3 different mumps-containing vaccines (MuCV) since 1990: monovalent mumps vaccine, measles-mumps (MM) vaccine, and measles-mumps-rubella (MMR) vaccine, and one dose MuCV (using MMR at 18 months) has been included in the EPI since 2007. MuCV effectiveness has been of concern following large-scale mumps outbreaks. In 2015, an outbreak of mumps occurred in a primary school, which allow us assess vaccine effectiveness of different MuCVs. All children in the school were studied as a retrospective cohort. Vaccination histories and case information were obtained from vaccination records and clinic/hospital logs. Parental questionnaires were used to confirm students' illnesses and calculate attack rate (AR). VE was assessed using the formula, VE = (AR in unvaccinated students- AR in the vaccinated students) / (AR in unvaccinated students). VEs of different type of MuCV were compared. In total, 283 students were identified as clinical mumps among the 2370 students, and 1908 students were included for MuCV VE assessment. 213 (including 21 [8.9%] patients) were 2-dose MuCV recipients (AR: 9.9%), 1165 (including 123 [51.9%] patients) were 1-dose recipients (AR: 10.6%), and 530 (including 93 [39.2%] patients) were unvaccinated (AR: 17.5%). VE was 44% for 2 doses and 40% for one dose. For one-MuCV-dose students, estimated mumps VE was 63% for vaccinated within 3 years (between vaccination and this outbreak); 50% for vaccinated within 3 to 5 years; and 34% for vaccinated more than 5 years. Comparing VE by vaccine type and 5-year interval since vaccination, VE for MMR was 60%, which was consistently higher than VE for monovalent mumps vaccine (22%) and MM (2%). This outbreak was associated with low and declining 1-dose MuCV effectiveness. China's immunization program should evaluate the potential of a 2-dose MMR schedule to adequately control mumps.


Transcriptional reprogramming of mature CD4⁺ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes.
TCRαβ thymocytes differentiate into either CD8αβ(+) cytotoxic T lymphocytes or CD4(+) helper T cells. This functional dichotomy is controlled by key transcription factors, including the helper T cell master regulator ThPOK, which suppresses the cytolytic program in major histocompatibility complex (MHC) class II-restricted CD4(+) thymocytes. ThPOK continues to repress genes of the CD8 lineage in mature CD4(+) T cells, even as they differentiate into effector helper T cell subsets. Here we found that the helper T cell fate was not fixed and that mature, antigen-stimulated CD4(+) T cells terminated expression of the gene encoding ThPOK and reactivated genes of the CD8 lineage. This unexpected plasticity resulted in the post-thymic termination of the helper T cell program and the functional differentiation of distinct MHC class II-restricted CD4(+) cytotoxic T lymphocytes.


Anxiety and depression in patients with pityriasis rosea compared to patients with tinea versicolor.
Few researchers have specifically evaluated how the quality of life of patients with pityriasis rosea (PR) and tinea versicolor (TV) are affected. There are even less studies exploring the psychological status of these patients. The objective of this study was to investigate and compare quality of life and psychological status of patients with PR and TV. Thirty-six patients with pityriasis rosea and 43 patients with tinea versicolor (N = 79) were selected for the study. All patients were required to complete Dermatology Life Quality Index (DLQI) and Hospital Anxiety and Depression (HAD), Hospital Anxiety and Depression-Depression (HAD-D), and Hospital Anxiety and Depression-Anxiety (HAD-A) scales. Both groups did not differ from each other with regard to DLQI, HAD-D, HAD-A, and total HAD scores (p > 0.05). With regard to cutoff points of HAD-A, 11 patients in the PR group and 15 patients in the TV group had anxiety. The number of patients with depression in pityriasis rosea and tinea versicolor groups were 11 and 13 respectively. Depression and anxiety scores were highly correlated with DLQI scores in both patients with PR and TV. Results of the present study indicate that patients with PR and TV are at risk for psychopathology. Uncertainties about the etiology and length of recovery period in PR and location of disease to visible parts and recurrent nature of the disease in TV groups might have affected the patients' psychological status.


Development of different diagnostic techniques for Endolimax piscium (archamoebae) and their applicability in Solea senegalensis clinical samples.
Systemic amoebiasis of sole is caused by Endolimax piscium, a cryptic parasitic archamoeba whose epidemiology and pathogeny are yet unknown. To establish reliable detection methods for this parasite, a battery of molecular diagnostic tools (ISH, PCR and qPCR) were developed and evaluated with a panel of clinical samples from symptomatic diseased fish and from apparently normal animals of different stocks. As there is neither enough background information on the epidemiology of the disease nor a validated reference method, comparison of tests used a composite reference method approach. The ISH technique was the most specific and sensitive in intestine samples and particularly useful as a reference confirmatory method, while the best method in muscle samples was qPCR. Application of the tests to asymptomatic fish demonstrated presence of parasites in a large proportion (>25%) of their intestines, suggesting that this is the point of entry of the amoebae and the initial stage in the development of the disease. The triggering factors that facilitate the breaching of the intestinal barrier by E. piscium, causing granulomatous lesions in other organs and systemic spreading, are not completely understood but our results point to the connective tissue as a preferential target for parasite development and migration.


Direct Multitype Cardiac Indices Estimation via Joint Representation and Regression Learning.
Cardiac indices estimation is of great importance during identification and diagnosis of cardiac disease in clinical routine. However, estimation of multitype cardiac indices with consistently reliable and high accuracy is still a great challenge due to the high variability of cardiac structures and the complexity of temporal dynamics in cardiac MR sequences. While efforts have been devoted into cardiac volumes estimation through feature engineering followed by a independent regression model, these methods suffer from the vulnerable feature representation and incompatible regression model. In this paper, we propose a semi-automated method for multitype cardiac indices estimation. After the manual labeling of two landmarks for ROI cropping, an integrated deep neural network Indices-Net is designed to jointly learn the representation and regression models. It comprises two tightly-coupled networks, such as a deep convolution autoencoder for cardiac image representation, and a multiple output convolution neural network for indices regression. Joint learning of the two networks effectively enhances the expressiveness of image representation with respect to cardiac indices, and the compatibility between image representation and indices regression, thus leading to accurate and reliable estimations for all the cardiac indices. When applied with five-fold cross validation on MR images of 145 subjects, Indices-Net achieves consistently low estimation error for LV wall thicknesses (1.44 ± 0.71 mm) and areas of cavity and myocardium (204 ± 133 mm2). It outperforms, with significant error reductions, segmentation method (55.1% and 17.4%), and two-phase direct volume-only methods (12.7% and 14.6%) for wall thicknesses and areas, respectively. These advantages endow the proposed method a great potential in clinical cardiac function assessment.


Epistatic interactions implicating dopaminergic genes in bulimia nervosa (BN): relationships to eating- and personality-related psychopathology.
We explored the influence of interactions between polymorphisms acting upon postsynaptic receptors (DRD2 TaqA1 rs1800497 and DRD4 7R) and dopamine regulators (COMT rs4680 and DAT1) on the expression of eating symptoms and personality traits in women with bulimia-spectrum eating disorders. We had 269 bulimic women provide blood for genetic assays, and measured eating-disorder symptoms and psychopathological traits using structured interviews and self-report questionnaires. We observed two epistatic interactions on symptom indices: interactions (in predicted directions) of DRD2 by DAT were seen on Body Mass Index (p=.023), and of DRD4 by COMT on self-harming behaviors (p=.014)--with genetic effects that would correspond to reduced dopamine transmission coinciding with more-pathological scores. Our findings suggest that genes acting in the dopamine system interact to influence both eating-related and personality psychopathology, with the result that lower levels of dopamine neuro-transmission correspond to increased psychopathology and body mass in women with bulimia-spectrum disorders. We discuss the implications of our observations.


[Biological characteristics of bone marrow mesenchymal stem cells and JAK2 mutation in myeloproliferative neoplasms].
To study the biological characteristics of bone marrow mesenchymal stem cells (BMSCs) and detect JAK2 mutation in BMSCs from myeloproliferative neoplasms (MPN) patients. JAK2 V617F mutation and exon 12 mutation in 70 MPN patients' blood or bone marrow samples were detected. Isolated BMSCs were then characterized their phenotype, mesenchymal differentiation capacity and existence of JAK2 mutation. BMSCs derived from the patients were similar with healthy donors in terms of morphology, surface antigen and differentiation ability. Of them, 38 patients' blood or bone marrow samples harbored JAK2 V617F, and identified that 3 V617F-negative-patients' samples existed JAK2 exon 12. No patients' BMSC harbored JAK2 mutation though their blood or bone marrow samples carried JAK2 mutation. BMSCs from MPN patients had similar biological characteristics with healthy donors. BMSCs from MPN patients known to bear JAK2 mutation in blood or bone marrow cells didn't carry the mutation.


IDH mutation is paradoxically associated with higher 18F-FDOPA PET uptake in diffuse grade II and grade III gliomas.
The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and 18F-FDOPA uptake on PET in newly diagnosed gliomas. A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone 18F-FDOPA PET at an initial stage before surgery and histological diagnosis. 18F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). Patients with IDH mutation showed higher 18F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). This study showed paradoxically higher 18F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of 18F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation.


Direct determination of volume- and time-dependence of alveolar surface tension in excised lungs.
We measured alveolar surface tension directly by observing the spreading properties of fluid droplets placed by micropipette within individual alveoli. Alveolar surface tension in excised rat lungs at total lung capacity and 37 degrees was 29.7 +/- 1.4 mN-m-1. In lungs held at functional residual capacity, surface tension changed slowly, rising to 9 mN-m-1 at 30 min with a subsequent approximately linear rise to 16 mN-m-1 at 115 min. Thereafter it rose more rapidly (20 mN-m-1 at 140 min), suggesting that it was not asymptotically approaching an equilibrium value.


Sun protection of children at the beach.
We wanted to determine the frequency with which sun protection measures are used by children at the beach. A cross-sectional study was undertaken that combined a brief, structured interview with direct observation of the sun protection methods (sunscreen, clothing, hats, shade) used for children at a public beach in Florida. Of the 139 children observed, 97 (69.8%) had some form of sun protection used on all three body regions (head, torso, legs), while only 8 (5.8%) had none of the three body regions protected. Sunscreen was the most common method of sun protection (84.9%), and other methods were less frequently used (shirt 11.5%, pants 26.6%, hat 8.6%, shade 14.4%). Sun protection use differed by sex, with girls having better protection of their head and torso, and boys slightly better protection of their legs. Using direct observation, we found that parents frequently use sun protection measures (mainly sunscreen) for their children while at the beach. Parents primarily rely on the use of sunscreen, rather than such measures as avoiding the sun, using shade, or protective clothing.


The state of diabetes care provided to Medicare beneficiaries living in rural America.
Diabetes poses a growing health burden in the United States, but much of the research to date has been at the state and local level. To present a national profile of diabetes care provided to Medicare beneficiaries living in urban, semirural, and rural communities. Medicare beneficiaries with diabetes aged 18-75 were identified from Part A and Part B claims data from 1999 to 2001. A composite of 3 diabetes care indicators was assessed (annual hemoglobin A1c test, biennial lipid profile, and biennial eye examination). Over 77% had a hemoglobin A1c test, 74% a lipid profile, and 69% an eye examination. Patterns of care were considerably different across the urban-rural continuum at the state, Census division, and regional levels. States in the northern and eastern portions of the country had higher indicator rates for rural than for urban residents. States in the South had much lower rates for rural residents than their urban counterparts. Despite these within-state differences, across-state comparisons found that several states tended to have low indicator rates in every level of the urban-rural continuum. A common feature of these states was the relatively high concentration of nonwhite beneficiaries. For example, southern states had much higher concentrations of nonwhite beneficiaries relative to other areas in the country and demonstrated low rates in every level of the urban-rural continuum. Urban-rural quality of care differences may be a function not just of geography but also of the presence of a large nonwhite population.


Changes in the hyaline articular cartilage after air exposure.
The changes of hyaline articular cartilage from rabbits after air exposure were evaluated. The knee joints were exposed to air for periods of thirty minutes to two hours. The animals were killed periodically, at three days, one week and three weeks postoperatively. After sacrifice, the cartilage was removed and prepared for study by light microscopy and electron microscopy. Exposure to room air for thirty minutes produced chondrocyte necrosis in the upper third of the cartilage, and exposure for 60 minutes or longer produced chondrocyte necrosis of the entire thickness of articular cartilage at three days after arthrotomy. But, three weeks after arthrotomy, we could not find any chondrocyte necrosis in any rabbits at varying periods of air exposure. There was no significant change in proteoglycan content between the aired and control cartilage. Exposing cartilage to air can cause transient and reversible cartilage damage. If these changes are not reversible, the orthopedic surgeon should consider avoiding the prolonged exposure of articular cartilage to air, since complete matrix disintegration is known to occur months after chondrocyte necrosis.


Comparing depressive symptoms in teenage boys and girls.
Symptoms of depression vary between the males and females. Depressed men show behaviors such as irritability, restlessness, difficulty in concentrating, and instead of the usual behaviors. Sleep disturbance is a common symptom in depressed men. Men are less likely to go to doctors and unconsciously show other behaviors such as anger instead of the sadness. It seems that considering depression as "feminine" is a great injustice toward male patients whom their illness will not be diagnosed nor treated. The sample consisted of 191 depressed adolescents, 108 males and 83 females aged 13-19 years old. Data collected for 10 years from 2005 to 2015 and their depressive symptoms were evaluated by the Beck Depression Inventory-Second Edition. Depressed girls felt sadness, guilt, punishment, worthlessness, low energy and fatigue, or more asthenia, whereas depressed boys have symptoms such as irritability, depression, suicidal thoughts, or desires to reduce their pleasure. The results of t-test showed that the difference between the total scores of boys and girls with depressive disorder (16.93) is significant at 0.001. F values for feeling sad (58.13), hatred of self (12.38), suicidal thoughts or desires (12.97), restlessness (17.35), and irritability (46. 41) were significant in the 0.001. Experiencing depression in boys and girls according to the role of gender was different. Gender can have an effective role in showing depression symptoms in adolescents.


Ceftriaxone penetration of tissues.
Ceftriaxone (Rocephin) has shown excellent tissue and body fluid penetration after a dose of 1-2 g: concentrations well above the minimal inhibitory concentrations of most pathogens responsible for infection are detectable for more than 24 h. Data from over 60 tissues were analyzed from the literature; a selection of comparative and noncomparative studies of clinical relevance is presented.


Next-Generation Allergen-Specific Immunotherapy for Japanese Cedar Pollinosis Using Molecular Approaches.
Japanese cedar (JC) pollinosis is the most major IgE-mediated type I allergic disease in Japan. Allergen-specific immunotherapy is the only curative treatment for allergic diseases. Subcutaneous immunotherapy and sublingual immunotherapy have been introduced in Japan for JC pollinosis, but do not avoid some adverse side effects, because the natural allergens used as tolerogens cross-link with specific IgE types on mast cells and basophils. To make immunotherapy for JC pollinosis safer, more effective and convenient, rice-based oral allergy vaccines using hybrid peptides composed of multiple T-cell epitopes or recombinant deconstructed hypoallergenic derivatives derived from major allergens - Cry j 1 and Cry j 2 - have been developed and their efficacy and safety evaluated by oral administration of transgenic rice seeds. Furthermore, recombinant modified JC allergens conjugated with various immunomodulatory molecules and DNA-based vaccines have been created and their efficacy assessed.


Calcium action on the membrane currents possessing the properties of mechano-electric transducer currents in inner hair cells of the Guinea-pig cochlea.
In free-standing hair bundle, depolarization to +80 mV evoked a stable outward current and repolarization to -80 mV evoked a transient inward current attributable to the opening of mechano-electric transducer channels. The study investigated the Ca2+ dependence of this transducer-like membrane current in isolated inner hair cells of guinea-pig cochlea. The amplitude of outward currents increased and the rate of inward current decay, corresponding to adaptation kinetics, decreasing as the extracellular Ca2+ concentrations lessened, whereas the amplitude of outward current decreased and an adaptation accelerated as the extracellular Ca2+ elevated. Treatment with the cAMP agonist, 8-bromo-cAMP, induced an effect similar to that caused by elevating the extracellular Ca2+.


Cell-mediated immunity in infertility.
A role of cell-mediated immunity in immunologic infertility is indicated by a number of animal immunization studies and by reported clinical associations between cellular immune responses and infertility. Furthermore, recent technical advances in the field of cellular immunology have enabled advanced studies on the cellular and soluble mediators of cell-mediated immune responses and their interactions with reproductive processes. In this article we review some of the recent technical and conceptual advances in cellular immunology, the classic literature on cellular immune responses in infertility, and recent evidence that certain products of activated lymphocytes and macrophages significantly affect reproductive functions.


Breakage and acceptability of a polyurethane condom: a randomized, controlled study.
Although the first commercial polyurethane condom was approved for use several years ago, no U.S. clinical trial has compared its performance to that of the latex condom. In a masked crossover study, 360 couples were randomized to use three polyurethane condoms and three latex condoms. After each use, couples recorded condom breaks, condom slips and other aspects of performance. At completion of the study, couples compared the sensitivity, ease of use, fit and lubrication of the two types of condoms. The clinical breakage rate of the polyurethane condom was 7.2%, compared with 1.1% for the latex condom (relative risk of 6.6, 95% confidence interval of 3.5-12.3). The complete slippage rate (combining incidents during intercourse and withdrawal) of the polyurethane condom was 3.6%, compared with 0.6% for the latex condom (relative risk of 6.0, 95% confidence interval of 2.6-14.2). Most male users preferred the sensitivity provided by the polyurethane condom to that of the latex condom. The clinical breakage rate of the polyurethane condom is significantly higher than that of the latex condom. However, nearly half of the users preferred the polyurethane condom, which provides an option for couples who have rejected conventional condoms or who cannot use latex products.


Providing insecticide treated bed nets in antiretroviral treatment clinics in Malawi: a pilot study.
HIV infection and malaria, two of the most common and important health problems in sub-Saharan Africa, have been demonstrated to have interactive pathology. In Malawi, where malaria is endemic, and antiretroviral therapy (ART) delivery is scaling up, we piloted integration of long-lasting insecticide-treated bednets (ITN) provision in three ART clinics. In July 2006, 1,910 ITNs were delivered to pilot sites, and ART clinic staff personnel were briefed on ITN provision and use of a monitoring system. Sites were assessed using a structured questionnaire in December 2006. During the pilot period, 1,282 ITNs were distributed to patients. A large proportion (70%) of ART patients at these sites received pilot study ITNs. Site adherence to the monitoring system was variable. Seventeen patients were interviewed, 14 of whom were ART patients who had received ITNs; 11 of these (79%) had slept under the net the previous night. This pilot demonstrates the feasibility of ITN distribution to patients attending ART clinics in Malawi. Programmatic and policy considerations for national roll-out include the need to: 1) adopt a standardized monitoring system, 2) develop information, education, and communication materials, 3) develop in-service training for ART clinicians, and 4) identify systems for forecasting, procuring and distributing ITNs.


The Role of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Type 2 Diabetes.
The role of GLP-1 agonists in the treatment of type 2 diabetes have been shown to be viable options for add-on therapy in diabetic patients, as well as potential monotherapy options. With six available GLP-1 agents, and new combination products in the pipeline, they are a promising drug class for type 2 diabetic patients, especially due to their extended dosing interval and potential weight loss benefits.


[Combination chemotherapy in osteogenic sarcoma: the Memorial Sloan-Kettering cancer center experience (author's transl)].
In 61 patients (pts.) with biopsy proven osteogenic sarcoma a disease free survival rate of > 80% was obtained using T-7 chemotherapy. This can be explained by successful eradication of pulmonary micrometastases with aggressive chemotherapy. The prognosis for pts. < 12 years was significantly improved since a higher dose off Methotrexate was used for this younger age group. The histologic effect of preoperative chemotherapy on the primary tumor is of prognostic value for the outcome of the disease. Pts. with good histologic effect on the primary tumor (grade III and IV effect) show a 100% disease free survival rate, whereas pts. with poor histologic effect (grade I and II effect) have a 50% chance to develop metastases. The role of cis platinum in future therapeutic trials is discussed based on the experience with cis platinum in phase II trials.


Chlormethiazole as a hypnotic in elderly patients: A systematic review and meta-analysis.
The study objective was to estimate the efficacy and safety of chlormethiazole in older adults experiencing insomnia (sleep disorder). We therefore systematically searched Medline, Scopus, the Cochrane Library, PsycINFO, Ovid, ZB MED and PMC through December 2021 for randomized-controlled trials including patients > 60 years old with insomnia treated with chlormethiazole. Standardized mean differences or odds ratios with 95% confidence intervals were calculated for the main outcome parameters: sleep duration, onset of sleep, quality of sleep, adverse events or drop-out rates compared with placebo and other drugs. Risk of bias was assessed using the Cochrane tool. Eight randomized-controlled trials with 424 patients were included. Chlormethiazole significantly increased the duration of sleep when compared with placebo (standardized mean difference = 0.61; 95% confidence interval = 0.11-1.11; p = 0.02). More patients receiving chlormethiazole had adequate quality of sleep than those receiving other drugs (odds ratio = 1.44; 95% confidence interval = 1.04-1.98; p = 0.03). No differences were found regarding the onset of sleep (standardized mean difference = 1.07; 95% confidence interval = 0.79-1.46; p = 0.65). Drop-out rates were significantly lower under chlormethiazole treatment when compared with other drugs (odds ratio = 0.51; 95% confidence interval = 0.26-0.99; p = 0.05) and did not differ from placebo treatment (odds ratio = 1.37; 95% confidence interval = 0.23-8.21; p = 0.73). Side-effects such as "hangover" and daytime drowsiness occurred less frequently during chlormethiazole treatment compared with other drugs in three out of four studies, but differences were not significant (odds ratio = 0.24; 95% confidence interval = 0.04-1.48; p = 0.12). In conclusion, chlormethiazole showed significant effects on the duration and the quality of sleep with better tolerability if compared with other drugs in older adults with insomnia.


Improving Endpoint Detection to Support Automated Systematic Reviews.
Authors of biomedical articles use comparison sentences to communicate the findings of a study, and to compare the results of the current study with earlier studies. The Claim Framework defines a comparison claim as a sentence that includes at least two entities that are being compared, and an endpoint that captures the way in which the entities are compared. Although automated methods have been developed to identify comparison sentences from the text, identifying the role that a specific noun plays (i.e. entity or endpoint) is much more difficult. Automated methods have been successful at identifying the second entity, but classification models were unable to clearly differentiate between the first entity and the endpoint. We show empirically that establishing if head noun is an amount or measure provides a statistically significant improvement that increases the endpoint precision from 0.42 to 0.56 on longer and from 0.51 to 0.58 on shorter sentences and recall from 0.64 to 0.71 on longer and from 0.69 to 0.74 on shorter sentences. The differences were not statistically significant for the second compared entity.


A century of influenza prevention in St. Louis.
The 1918 pandemic of influenza in St. Louis was ameliorated by the public health efforts of the City Health Department. At the time, St. Louis was the sixth largest city in the US; among the ten largest cities, St. Louis had the fewest influenza cases and deaths. Closing schools, churches, theaters, and other public meeting places reduced the severity of the pandemic in St. Louis. The benefits of contemporary influenza vaccines to prevent influenza and economic disruption are summarized.


[Comparison of lidocaine and urapidil for prevention of hemodynamic response to tracheal intubation in patients in general good health].
To compare the efficacy of endovenous administration of 0.5 mg/kg-1 of urapidil to 1 mg/kg-1 of lidocaine for attenuating hemodynamic response to laryngoscopy and tracheal intubation. Study of 40 ASA I and II patients with normal blood pressure undergoing elective surgery under general anesthesia with orotracheal intubation. The patients were randomly assigned to two groups to receive either 0.5 mg/kg-1 of urapidil or 1 mg/kg-1 five minutes before anesthetic induction. Anesthesia was provided with 0.04 mg/kg-1 of midazolam, 2 micrograms/kg-1 of fentanyl, 2 mg/kg-1 of propofol, 0.1 mg/kg-1 of vecuronium before proceeding to orotracheal intubation, after electromyographic determination of neuromuscular response with T1 less than 5%, and laryngoscopy. Heart rate, systolic, diastolic and mean pressures, and the product of heart rate and mean arterial pressure (HR x MAP) were recorded at the following times: baseline (before administering either lidocaine or urapidil), after induction, after laryngoscopy and intubation, and 3 minutes and 5 minutes after intubation. ASA classification, age, sex and weight were similar in the two groups. Heart rate immediately after intubation, and after 3 and 5 minutes was significantly lower in the lidocaine group. Likewise HR x MAP immediately after intubation and 3 minutes later was significantly lower in the patients who received lidocaine. In healthy ASA I and II patients with normal blood pressure, a dose of 1 mg/kg-1 of lidocaine provided better protection against the hemodynamic response to laryngoscopy and tracheal intubation than does 0.5 mg/kg-1 of urapidil.


Chemiluminescent and enzyme-linked immuno assays for sensitive detection of human IFN-gamma.
We have produced and characterized 4 mAbs to human IFN-gamma and established sensitive, non-radioactive immuno-assays. The first two assays use microtiter plates as the solid phase and enzymes or chemiluminescence (acridinium ester) for development. The use of chemiluminescence instead of peroxidase increased the sensitivity of the assay by a factor of about 75. The third and the fourth assays utilize polystyrene beads as the solid phase and enzymes or acridinium ester for development. The use of beads also increased the sensitivity of detection. The most sensitive IFN-gamma detection was achieved by the combination of bead with acridinium ester. In this configuration we were able to detect about 0.2 pg/ml IFN-gamma (1/250th of a unit). These chemiluminescent immunoassays (CLIA) appear to be more sensitive than existing ELISAs or radioimmunoassays and may find new application areas.


The influence of traditional religion on fertility regulation among the Kassena-Nankana of northern Ghana.
This article presents findings from a study of the influence of traditional religion on reproductive preferences of Kassena-Nankana lineage heads in northern Ghana. Seven reproductive preference questions were administered to nine lineage heads who are primary practitioners of the cult of soothsaying. With the assistance of soothsayers, interviews were repeated in conjunction with the invocation of religious rites in order to determine the views of ancestral spirits on the seven questions. Pairs of lineage head and ancestral interviews are compared to determine the role of traditional religion in shaping male reproductive preferences. Interview pairs reflect a shared preference for sons, large compounds, and a growing lineage. Findings nonetheless show that some ancestral spirits want small families, some even wanting fewer children than corresponding lineage heads. Spiritual consultations are nondogmatic and open to external ideas and influences, suggesting that family planning introduction will not encounter systematic religious opposition among the Kassena-Nankana.


The presence of Torque teno virus in chronic obstructive pulmonary disease.
Torque Teno Virus (TTV) has been identified as transfusion-transmitted virus in humans, initially. Although TTV viremia is extremely common in the general population worldwide, there is no direct causal evidence linking TTV infection to specific clinical manifestations. Our hypothesis was that TTV might play a role in Chronic obstructive pulmonary disease (COPD) by inducing inflammatory mechanisms previously identified. The study was conducted on 57 COPD patients and 39 healthy control groups. COPD patient groups included: the patients (n:20) with exacerbation needed noninvasive ventilation, the patients (n:19) who received only medical treatment, and the invited patients (n:18) for outpatient control. Serum samples were collected from patients and voluntary blood donors. TTV DNA quantification was carried out with a real time PCR by the hybridization probe system and viral load was interpreted through the crossing point value. TTV DNA was detected in the majority of both patients and healthy control groups. The prevalence was 94.4% (17/18) in patients for outpatient control, 94.7% (18/19) in patients who received only medical treatment, 100% (20/20) in patients with exacerbation needed noninvasive ventilation and 84.6% (33/39) in healthy controls. This difference was not statistically significant. However, CP values was statistically different in all the patient groups from the control group. TTV DNA prevalence was higher in patients than healthy individuals. More interesting thing, viral load was highest in the patients with exacerbation needed noninvasive ventilation. As a result, TTV may be associated with COPD and the severity of it.


The effectiveness of PTSD treatment for adolescents in the juvenile justice system: A systematic review.
The objective of this study was to systematically review existing empirical evidence on the effectiveness of trauma-specific treatment for justice-involved adolescents and evaluate the impact of the interventions on the reduction of posttraumatic stress disorder (PTSD) symptoms, co-occurring mental health symptoms, and juvenile justice-related outcomes. A systematic literature search was conducted using a four-step process. Studies were included if they used a manualized, trauma-specific treatment with at least one control or comparison group and a sample comprised exclusively of justice-involved adolescents. In total, 1,699 unique records were identified, and 56 full-text articles were reviewed, of which 7 met the criteria for inclusion. Trauma-specific interventions led to a decrease in PTSD symptoms compared with a control group in four of seven studies, and two studies also demonstrated a reduction in trauma-related depressive symptoms. Finally, juvenile justice-related outcomes were measured in only four studies, with one study finding moderately reduced rates of delinquent behavior and recidivism following trauma-specific treatment. The results from this systematic review suggest that trauma-specific treatment interventions have promising effects for justice-involved adolescents. However, the results reveal a dearth of quality intervention research for treating youths with histories of trauma in the justice system. Significant gaps in the literature are highlighted, and suggestions for future directions are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Aplasia cutis congenita of the scalp in an infant exposed to valproic acid in utero.
We report a newborn with isolated aplasia cutis congenita of the scalp whose mother was treated with valproic acid during pregnancy. Aplasia cutis congenita has been described in infants exposed in utero to antithyroid drugs, but has not been related to other tetratogenic agents. Fetal exposure to valproic acid is known to increase the risks of spina bifida and other midline defects. Interestingly, aplasia cutis congenita of the scalp is regarded as a cutaneous marker for neural dysraphism. However, this defect of the scalp and valproic acid intake during pregnancy may be a random association and similar observations are needed to suggest causality.


Morning reduction of cerebral vasomotor reactivity.
We measured cerebral vasomotor reactivity during normoventilation, hyperventilation (hypocapnia), and breathing of 6% CO2 (hypercapnia) in 20 normal subjects during the hours of 6 to 8 AM, 1 to 3 PM, and 7 to 9 PM. Cerebral vasomotor reactivity was calculated, using transcranial Doppler, as percent change in the mean blood flow velocity of the middle cerebral artery per mm Hg change in end-tidal CO2 during hypocapnia and hypercapnia. Vasomotor reactivity during hypercapnia was lower in the morning (1.72 +/- 0.66 %/mm Hg) than in the afternoon (2.34 +/- 0.74 %/mm Hg, p < 0.01) and evening (2.31 +/- 0.56 %/mm Hg, p < 0.001). Vasomotor reactivity during hypocapnia did not vary significantly during the three periods (2.34 +/- 0.59 %/mm Hg in the morning, 2.43 +/- 0.51 %/mm Hg in the afternoon, and 2.26 +/- 0.52 %/mm Hg in the evening). This reduced morning response to hypercapnia suggests diminished vasodilator reserve during this period, and may be related to the increased stroke risk during the morning hours.


Connectomic analysis of unilateral dual-lead thalamic deep brain stimulation for treatment of multiple sclerosis tremor.
Tremor is a common symptom in multiple sclerosis and can present as a severe postural and action tremor, leading to significant disability. Owing to the diffuse and progressive nature of the disease, it has been challenging to characterize the pathophysiology underlying multiple sclerosis tremor. Deep brain stimulation of the ventralis intermedius and the ventralis oralis posterior thalamic nuclei has been used to treat medically refractory multiple sclerosis tremors with variable results. The aim of this study was to characterize multiple sclerosis tremor at the network level by applying modern connectomic techniques to data from a previously completed single-centre, randomized, single-blind prospective trial of 12 subjects who were treated with unilateral dual-lead (ventralis intermedius + ventralis oralis posterior) thalamic deep brain stimulation. Preoperative T1-weighted MRI and postoperative head CTs were used, along with applied programming settings, to estimate the volume of tissue activated for each patient. The volumes of tissue activated were then used to make voxel-wise and structural connectivity correlations with clinically observed tremor suppression. The volume of the tissue-activated analyses identified the optimal region of stimulation at the ventralis oralis posterior ventralis intermedius border intersecting with the dentato-rubro-thalamic tract. A regression model showed strong connectivity to the supplemental motor area was positively associated with tremor suppression (r = 0.66) in this cohort, whereas connectivity to the primary motor cortex was negatively associated with tremor suppression (r = -0.69), a finding opposite to that seen in ventralis intermedius deep brain stimulation for essential tremor. Comparing the structural connectivity to that of an essential tremor cohort revealed a distinct network that lies anterior to the essential tremor network. Overall, the volumes of tissue activated and connectivity observations converge to suggest that optimal suppression of multiple sclerosis tremor will likely be achieved by directing stimulation more anteriorly toward the ventralis oralis posterior and that a wide field of stimulation synergistically modulating the ventralis oralis posterior and ventralis intermedius nuclei may be more effective than traditional ventralis intermedius deep brain stimulation at suppressing the severe tremors commonly seen in complex tremor syndromes such as multiple sclerosis tremor.


Keratinocyte growth factor and its receptor expression in chronic otitis media with and without cholesteatoma.
Chronic suppurative otitis media (CSOM) with and without cholesteatoma is regarded as chronic inflammation of the middle ear and mastoid mucosa that can be associated with the presence of granulation tissue and infection, which can lead to ossicular damage and hearing loss, but it is commonly known that cholesteatoma behaves aggressively. Both lesions appear to contain a predominant population of inflammatory cells, among which proinflammatory cytokines secreting keratinocyte growth factor (KGF) and its receptor (KGFR). No clear difference was demonstrated between these entities. The purpose of this study was to investigate the potential influence of KGF and KGFR in increased epithelial-cell proliferation of chronic otitis media (COM) with cholesteatoma in contrast to COM without cholesteatoma (CSOM), particularly in the granulative form, and to compare the rate of proliferation activity of epithelial cells using the Ki-67 epithelial proliferation marker expression. We analyzed 105 ears with cholesteatoma vs. 53 ears with CSOM without cholesteatoma using our KGF and KGFR variables, and the ratio of proliferating epithelial cells using Ki-67. The percentage of the specimens expressing KGF and KGFR was compared between the two groups for statistical significance using the Pearson's chi-square test. Immunohistochemical staining was conducted and the proportion of the cells staining positive for the nuclear antigen Ki-67 was evaluated in a quantitative and visual way, using light microscopes. KGF was positive in 88.57% of cholesteatoma and was positive in 41.51% CSOM without cholesteatoma specimens (cholesteatoma vs. CSOM, p=0.001). The positive rate of KGFR in the CSOM group was 33.96% compared to those in cholesteatoma, which was 60.95%. Compared to the cholesteatoma specimens, a significantly smaller number of Ki-67 labeling index was detected in CSOM specimens. Our results indicated that the abnormal behavior of the cholesteatoma epithelium seems to be induced by the paracrine interaction between KGF and KGFR. Furthermore, we found that cholesteatoma expressing both KGF and KGFR had high Ki-67 index, which correlated with its aggressiveness. These findings suggest that excessive KGF and KGFR synthesis may contribute to the hyperproliferative state in cholesteatoma and could explain the pathological difference between cholesteatoma and CSOM.


Aphasia and thalamotomy: important issues.
Patients may present with classical symptoms suggesting aphasia following thalamotomy (repetition, comprehension, fluency and naming abnormalities). They may also present with 'freezing of speech', and this symptom should not be considered as a speech disorder or a symptom of Parkinson's disease progression, without careful testing to rule out language deficits, particularly dysfluency. There are important issues related to all language complications of thalamotomy, including (1) the time course of problems following surgery, (2) the impact of preexistingspeech problems, (3) the importance of the size and location of lesions, (4) the potential circuits important in the pathogenesis of a thalamic language disturbance and (5) whether laterality makes a difference (left- versus right-sided thalamic lesions). As more centers switch from thalamotomy to deep brain stimulation, the issues regarding aphasia will need to be addressed.


Similar effects of recombinant human insulin-like growth factor-I and II on cellular activities in flexor tendons of young rabbits: experimental studies in vitro.
To improve the understanding of factors with the potential of affecting the healing of flexor tendons, this study compared the cellular effects of recombinant human insulin-like growth factor-II with those of recombinant human insulin-like growth factor-I in matched pairs of deep flexor tendons of young rabbits. Dose-response effects on the synthesis of DNA and matrix proteins of either factor alone or in combination were investigated in short-term culture, and effects on synthesis and turnover of matrix components were compared in long-term culture. Both factors stimulated proteoglycan, collagen, noncollagen protein, and DNA synthesis in a dose-dependent manner in the range of 10-500 ng/ml. Insulin-like growth factor-I increased proteoglycan synthesis to as much as six times that of controls but was less potent than insulin-like growth factor-II. Both factors stimulated increased cell proliferation by as much as five times compared with control values, but insulin-like growth factor-I was more potent than insulin-like growth factor-II. The two factors in combination did not enhance the synthesis of matrix proteins and DNA as compared with either factor alone. Insulin-like growth factor-I counteracted the decrease in collagen synthesis and stimulated protein synthesis to a higher degree than insulin-like growth factor-II in long-term culture. Both factors had similar effects on matrix turnover, with estimated half times (t1/2) for elimination of newly labeled proteoglycans and proteins of 11 and 8 days, respectively. Insulin-like growth factor-II is capable of stimulating cell proliferation and matrix metabolism in tendon explants of young rabbits at levels similar to those of insulin-like growth factor-I; in combination, the two growth factors are unable to augment the stimulatory effects of either of the factors alone.


Postoperative assessment of surgical clip position in 16 dogs with cancer: a pilot study.
Metallic hemoclips or surgical staples were inserted in 16 tumor-bearing dogs at the time of surgical resection of the tumor. Orthogonal radiographs were taken immediately postoperatively and after wound healing to visualize the location and number of hemoclips or metallic staples. A shift in hemoclip/staple position was identified in nine dogs, mainly from positioning during radiography. In three dogs, an absolute shift in marker position was identified. Based on this study, it appears that the placement of surgical clips is potentially useful in identifying the tumor bed, which may be of benefit in establishing radiation treatment fields.


Acromial morphotype in the young asymptomatic athletic shoulder.
Several studies have documented an association between the type III acromion and rotator cuff tears. However, controversy exists as to whether the shape of the acromion is an innate anatomic characteristic. The purpose of this study was to evaluate the prevalence of the type III acromion in young asymptomatic athletes. Bilateral supraspinatus outlet radiographs were obtained in 100 Division 1 collegiate athletes (average age, 19.9 years). Only 4 (2%) of 200 shoulders were found to have a type III acromion by use of the standard subjective Bigliani classification. Eight (4%) acromion were found to be type III by the use of previously published objective criteria for acromial measurement. Our results show the type III acromion to be relatively rare in asymptomatic, young athletes, but the incidence of type III acromion in a general population of both young and older individuals is still not completely understood. However, our results accentuate the possibility that the higher incidence of type III acromion seen in older populations may in fact be related to secondary acromial changes.


A new J.E probe for measurement of spatial profiles of power absorption in RF produced plasma.
This paper reports an indigenously developed probe for the measurement of spatial profiles of the absorbed/generated RF power density Pabs (W/m3) in RF discharges. The technique utilizes a calibrated current (J) probe based on the Rogowski coil principle and an electric field (E) probe based on capacitive coupling, both integrated into a single probe called the J.E probe. Various aspects of the probe, such as its design, fabrication, calibration, and limitations, were resolved before it was used for obtaining axial profiles of RF power absorption/generation. Also presented are the first experimental results for the absorbed power density profiles at the fundamental (13.56 MHz) and harmonic (27.12 MHz) along the length of a capacitively coupled discharge. The axial scans between the powered and grounded electrode were taken at different argon gas pressures (10-800 mTorr) at a fixed RF power of 10 W. Detailed analysis of the results shows that even for systems with large electrode gaps, i.e., plasmas with long bulk plasma regions, practically all the fundamental power is absorbed in a narrow edge region near the powered electrode, irrespective of the pressure. Absorption is high near the RF electrode since the RF fields peak in this region. Another important conclusion is that stochastic absorption of the fundamental and harmonic generation proceeds fairly efficiently in the vicinity of the powered electrode even at high pressures. It may be mentioned that the probe technique introduced here is the first of its kind, and although there is considerable scope for miniaturization, it has, nonetheless, provided some key insights into the nature of RF power absorption in capacitive discharges.


The reproductive lifespan of Onchocerca volvulus in West African savanna.
The epidemiological model ONCHOSIM--a model and computer simulation program for the transmission and control of onchocerciasis--has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on different lifespan quantifications were compared with the results of longitudinal skin-snip surveys undertaken in 4 reference villages during 13 to 14 years of successful vector control in the Onchocerciasis Control Programme in West Africa. Good fits between predicted and observed trends in skin microfilarial loads could be obtained for all villages. It is concluded that the reproductive lifespan of the savanna strain of O. volvulus lies between 9 and 11 years, and that 95% of the parasites reach the end of reproduction before the age of 13 to 14 years.


[Modeling of mechanoelectric coupling in cardiomyocytes in norm and pathology].
We developed mathematical models of the electromechanical function of cardiomyocytes and the simplest mechanically heterogeneous myocardial systems, muscle duplexes. By means of these models we studied the contribution of mechanoelectric feedbacks to the contractile activity of the myocardium in norm and pathology. In particular, we simulated and clarified the effects of mechanical conditions on both the form and the duration of the action potential during contractions. From this standpoint different kinds of myocardium mechanical heterogeneity were analyzed. As we have established, the latter can play both a positive and a negative role, depending on the distribution of mechanical nonuniformity and the sequence of activation of heterogeneous myocardium system elements. By means of the same models, we studied the contribution of mechanical factors to the arrhythmogenicity in the case of the cardiomyocyte calcium overload caused by the attenuation of the sodium-potassium pump and outlined the ways for correcting the contractile function in these disturbances.


[Surgical management of nontraumatic corneal perforations: an 8-year retrospective study].
Treatment of nontraumatic corneal perforation is a difficult task. The aim of our study was to retrospectively analyze predisposing conditions leading to perforation, surgical treatments, and visual outcomes. Fifty-six patients were admitted in our department for a nontraumatic corneal perforation between 1997 and 2004. Mean patient age was 69 years (range, 16-95 years) and the mean follow-up was 20.5 months (range, 6-96 months). The diseases associated with perforations were neurotrophic ulcer in 24 cases (43%), peripheral immunologic ulcer in ten cases (18%), dry eye in six cases (11%), and infectious keratitis in seven cases (13%). All patients had specific adapted medical treatment before surgery. As a first procedure, we used cyanoacrylate glue in 14 cases (50% anatomic success), multilayer amniotic membrane transplantation in 23 cases (100% anatomic success), conjunctival flap in six cases, peripheral lamellar graft in three cases (33% anatomic success), emergency penetrating keratoplasty in 13 cases (31% anatomic success), and one patient's eye had to be eviscerated. Several surgical procedures were necessary in 16 cases (28%), nine patients needing total conjunctival flap at the end. We were able to achieve tectonic stability in 91% of eyes and 32% of patients recovered useful visual acuity between 20/400 and 20/50. Amniotic membrane transplantation is an effective method for managing corneal perforations and usually does not need a further reconstructive procedure. Visual outcome is poor when peripheral or central keratoplasty are needed. We recommend a conjunctival flap when descemetocele or perforation recurs despite previous surgical management.


An Iron-Sulfur Cluster with a Highly Pyramidalized Three-Coordinate Iron Center and a Negligible Affinity for Dinitrogen.
Attempts to generate open coordination sites for N2 binding at synthetic Fe-S clusters often instead result in cluster oligomerization. Recently, it was shown for Mo-Fe-S clusters that such oligomerization reactions can be prevented through the use of sterically protective supporting ligands, thereby enabling N2 complex formation. Here, this strategy is extended to Fe-only Fe-S clusters. One-electron reduction of (IMes)3Fe4S4Cl (IMes = 1,3-dimesitylimidazol-2-ylidene) forms the transiently stable edge-bridged double cubane (IMes)6Fe8S8, which loses two IMes ligands to form the face-bridged double-cubane, (IMes)4Fe8S8. The finding that the three supporting IMes ligands do not confer sufficient protection to curtail cluster oligomerization prompted the design of a new N-heterocyclic carbene, SIArMe,iPr (1,3-bis(3,5-diisopropyl-2,6-dimethylphenyl)-2-imidazolidinylidene; abbreviated as SIAr), that features bulky groups strategically placed in remote positions. When the reduction of (SIAr)3Fe4S4Cl or [(SIAr)3Fe4S4(THF)]+ is conducted in the presence of SIAr, the formation of (SIAr)4Fe8S8 is indeed suppressed, permitting characterization of the reduced [Fe4S4]0 product. Surprisingly, rather than being an N2 complex, the product is simply (SIAr)3Fe4S4: a cluster with a three-coordinate Fe site that adopts an unusually pyramidalized geometry. Although (SIAr)3Fe4S4 does not coordinate N2 to any appreciable extent under the surveyed conditions, it does bind CO to form (SIAr)3Fe4S4(CO). This finding demonstates that the binding pocket at the unique Fe is not too small for N2; instead, the exceptionally weak affinity for N2 can be attributed to weak Fe-N2 bonding. The differences in the N2 coordination chemistry between sterically protected Mo-Fe-S clusters and Fe-only Fe-S clusters are discussed.


The effects of commercial local anaesthetic solutions on the isolated rabbit ear artery.
The response of an isolated artery preparation to commercial local anaesthetic solutions containing either prilocaine or lignocaine in the presence of adrenaline or noradrenaline has been examined. In low doses, both local anaesthetics were found to augment the constrictor response to adrenaline, wheras at higher doses the effect of adrenaline was significantly depressed by them. In contrast, noradrenaline's vasoconstrictor response was not potentiated by low doses of lignocaine, although higher dose levels caused a significant reduction in its vasoconstrictor effect.


Fabry disease due to G171S GLA mutation: An atypical small nerve fiber sparing variant?
To describe the ocular manifestations and in vivo confocal microscopic findings in a patient carrying the recently described hemizygous G171S GLA gene mutation. A 63-year-old Albanian male patient was evaluated for cataract surgery. Anamnesis showed pacemaker implantation in left ventricular hypertrophy, chronic kidney disease, family history for kidney transplantation, and late onset of sporadic acroparesthesias. Bilateral cornea verticillata, and increased tortuosity in conjunctival and retinal vessels were present. In vivo confocal microscopy revealed clusters of hyper-reflective corneal epithelial cells centripetally extending from the limbus. Interestingly, the nerve fiber number, density, and length in the corneal sub-basal nerve plexus were preserved. Alpha-galactosidase A activity was almost absent and hemizygous c.511G>A mutation (G171S - p.Gly171Ser) of the GLA gene was identified. The patient was referred for initiation of enzyme replacement therapy, and genetic counseling was recommended for at-risk family members. This is the third reported case of Fabry disease due to GLA G171S mutation. All patients are of Albanian descent. Cornea verticillata and vascular anomalies remain common ocular manifestations, as well as cardiac and renal involvement. Confirming its pathogenicity, this mutation results in a "classic" Fabry disease phenotype, but it seems to be associated with a relative small nerve fiber sparing that may delay a correct diagnosis. The diagnosis of Fabry disease still remains challenging due to its clinical heterogeneity, but a thorough ophthalmological examination can promote early detection and, consequently, early initiation of enzyme replacement therapy.


Redirecting adult mesenchymal stromal cells to the brain: a new approach for treating CNS autoimmunity and neuroinflammation?
Mesenchymal stromal cells or stem cells (MSCs) have been shown to participate in tissue repair and are immunomodulatory in neuropathological settings. Given this, their potential use in developing a new generation of personalized therapies for autoimmune and inflammatory diseases of the central nervous system (CNS) will be explored. To effectively exert these effector functions, MSCs must first gain entry into damaged neural tissues, a process that has been demonstrated to be a limiting factor in their therapeutic efficacy. In this review, we discuss approaches to maximize the therapeutic efficacy of MSCs by altering their intrinsic trafficking programs to effectively enter neuropathological sites. To this end, we explore the significant role of chemokine receptors and adhesion molecules in directing cellular traffic to the inflamed CNS and the capacity of MSCs to adopt these molecular mechanisms to gain entry to this site. We postulate that understanding and exploiting these migratory mechanisms may be key to the development of cell-based therapies tailored to respond to the migratory cues unique to the nature and stage of progression of individual CNS disorders.


Treatment of a giant ascending aortic pseudoaneurysm presenting as a presternal pulsatile protrusion almost perforating through the skin.
Aortic pseudoaneurysms have the potential for eroding bony structures in the chest, including the sternum, over time. Here, we report the case of a 54-year old woman with a giant pseudoaneurysm of the ascending aorta, 19 years after aortic root (mechanical conduit) and hemiarch replacement. The patient presented to her primary-care physician with a pulsatile presternal subcutaneous protrusion in the midline of her median sternotomy scar. We performed a challenging midline resternotomy after the establishment of a surgical safety net for cerebral and visceral organ protection followed by a supracoronary ascending and hemiarch replacement including a reinsertion of the coronary ostia employing selective antegrade cerebral perfusion and mild systemic hypothermic circulatory arrest. We discuss here the specific surgical considerations of this case.


High prevalence of hepatitis C virus type 5 in central France evidenced by a prospective study from 1996 to 2002.
From 1996 to 2002, hepatitis C virus (HCV) typing was prospectively performed for 1,281 unselected HCV-infected and viremic patients, irrespective of their clinical status. Eighty-three patients (6.5%) were coinfected with human immunodeficiency virus (HIV) and HCV. A total of 1,195 strains were identified by a serotype screening (Murex HCV Serotyping 1-6 assay) and/or genotyping (Inno-LiPA HCV II) test. The distribution of HCV types showed an unusually high rate of type 5 (14.2%) that was stable over time and was the third most frequent type, after type 1 (59.1%) and type 3 (15.1%). HCV type 5 was more frequent in patients who were older than 50 (P = 10(-6)), but its frequency did not differ significantly by gender (P = 0.21). Serotyping was performed for 1,160 strains but failed for 30.2% of them. The efficiency depended on HIV status (for HCV-HIV-coinfected patients, half of the strains were untypeable) and HCV type. Genotyping was performed for 428 samples, with an overall efficiency of 99.3%. It failed in three cases, which were subsequently identified as HCV type 2. Serotyping and genotyping results for 39 patients showed discrepancies between the two methods for 4 patients, who had HCV type 2, type 6, or mixed infections. Thus, HCV type 5 may also be encountered frequently in Western countries. Its apparent confinement to a restricted area raises the question of how it emerged and underscores the need for further studies of HCV type prevalence, routes of transmission, pathogenicity, and responses to treatment.


Suicide attempts in major depressive episode: evidence from the BRIDGE-II-Mix study.
The Bipolar Disorders: Improving Diagnosis, Guidance, and Education (BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as suicidality. A total of 2,811 subjects were enrolled in this multicenter cross-sectional study. Psychiatric symptoms, and sociodemographic and clinical variables were collected. The analysis compared the characteristics of patients with MDE with (MDE-SA group) and without (MDE-NSA) a history of suicide attempts. The history of suicide attempts was registered in 628 patients (22.34%). In the MDE-SA group, women (72.5%, p = 0.028), (hypo)mania in first-degree relatives (20.5%, p < 0.0001), psychotic features (15.1%, p < 0.0001), and atypical features (9.2%, p = 0.009) were more prevalent. MDE-SA patients' previous responses to treatment with antidepressants included more (hypo)manic switches [odds ratio (OR) = 1.97, 95% confidence interval (CI): 1.58-2.44, p < 0.0001], treatment resistance (OR = 2.07, 95% CI: 1.72-2.49, p < 0.0001), mood lability (OR = 1.98, 95% CI: 1.65-2.39, p < 0.0001), and irritability (OR = 1.80, 95% CI: 1.48-2.17, p < 0.0001). Multivariate analysis evidenced that risky behavior, psychomotor agitation and impulsivity, and borderline personality and substance use disorders were the variables most frequently associated with previous suicide attempts. In the MDE-SA group, 75 patients (11.9%) fulfilled Diagnostic and Statistical Manual (DSM)-5 criteria for MDE with mixed features, and 250 patients (39.8%) fulfilled research-based diagnostic criteria for a mixed depressive episode. Important differences between MDE-SA and MDE-NSA patients have emerged. Early identification of symptoms such as risky behavior, psychomotor agitation, and impulsivity in patients with MDE, and treatment of mixed depressive states could represent a major step in suicide prevention.


Effect of a denture adhesive on the satisfaction and kinesiographic parameters of complete denture wearers: a cross-over randomized clinical trial.
The aim of the present study was to assess the effect of a denture adhesive (DA) on patient satisfaction and kinesiographic parameters of complete denture wearers by a cross-over study. Fifty edentulous patients received a set of new complete dentures. After an adaptation period, the participants were enrolled in the trial and randomized to receive a sequence of treatment protocols: Protocol 1- DA use during the first 15 days, followed by no DA for the next 15 days; Protocol 2- no DA during the first 15 days, followed by use of DA for the next 15 days. Outcomes were assessed after 15 days of each sequence of treatment. A questionnaire was used to assess the patients' satisfaction. A kinesiograph was used to record mandible movements and patterns of maxillary complete denture movement during chewing. The Wilcoxon test (α=0.05) and a paired sample t-test (α=0.05) were used to compare satisfaction levels and kinesiographic data, respectively. Use of DA improved the overall level of patient satisfaction (p<0.001). The kinesiographic recordings revealed a significant increase (1.7 mm) in vertical mandible movements (p<0.001) during chewing and a lower (0.3 mm) vertical intrusion of the maxillary complete dentures (p=0.002) during chewing after using the DA. Use of DA in complete denture wearers improved the patients' satisfaction and altered mandible movements, with increases in vertical movements during chewing and less intrusion of maxillary complete dentures.


Thoracic helical CT.
Helical CT depicts small pulmonary nodules not seen at conventional CT by elimination of respiratory misregistration and thorough analysis of a contiguous data volume. Pulmonary lesions can be analyzed in detail with use of retrospective reconstruction of the data volume. Multiplanar and three-dimensional images of lung masses and arteriovenous malformations are free of motion artifacts. The airways are clearly depicted by helical CT, a capability that enhances the radiologic evaluation of patients with hemoptysis, bronchial strictures, tumors, and recent lung transplantation. In comparison to conventional CT, helical CT provides a more consistent level of vascular enhancement because of the shortened acquisition time. Clinical applications include the detection of central pulmonary thromboemboli and the assessment of aortic aneurysms and dissections.


Mechanisms of splenic hypertrophy following hepatic resection.
Following hepatic resection, liver regeneration has been associated with concurrent splenic hypertrophy. The mechanisms of this phenomenon are unknown, may be multiple and include: splanchnic sequestration caused by a reduction in the hepatic mass; hepatic growth factors that may indirectly act on the spleen, and the redistribution of the total reticuloendothelial system. Seventy-five patients (40 males; median age: 60 years) who underwent minor (16%) or major (84%) hepatectomy between September 2004 and October 2009 were included. Prospective measurements of liver and spleen volumes were obtained preoperatively and postoperatively 1 month after hepatectomy using computed tomography (CT). The future remnant liver volume (RLV) was calculated on preoperative CT and the extent of resection was expressed as the RLV divided by total liver volume (TLV). Liver and spleen hypertrophy were expressed according to the absolute gain or relative increase in the initial volumes (%).The presence of fibrosis >F1, associated extrahepatic resection (except minor resections), and previous hepatectomy (major or minor) within 3 months represented exclusion criteria. Mean ± standard deviation (SD) liver volume at 1 month was higher than RLV (1187 ± 286 cm(3) versus 764 ± 421 cm(3) ; P < 0.001). Mean ± SD splenic volume increased from 252 ± 100 cm(3) preoperatively to 300 ± 111 cm(3) at 1 month (P < 0.001). Liver and splenic hypertrophy were significant after major hepatectomies (+100% and +26%, respectively; P < 0.001), but not after minor hepatectomies. Liver hypertrophy was inversely correlated to RLV/TLV (r = -0.687, P < 0.001). Splenic hypertrophy was not correlated to RLV/TLV. Liver and splenic hypertrophy were linearly correlated (r = 0.495, P < 0.001). Neoadjuvant chemotherapy (n = 37), preoperative portal vein embolization (n = 10) and postoperative complications (overall: n = 25; major: n = 10; infectious: n = 6) had no impact on hepatic or splenic hypertrophy. Splenic hypertrophy occurred after major hepatectomy, but was not correlated to the extent of resection, by contrast with liver hypertrophy. Nevertheless, there was a linear correlation between splenic and liver hypertrophy. This correlation suggests the hypothesis of a splenic action of hepatic growth factors or a redistribution of the total reticuloendothelial system rather than an effect of reduction of the portal bed or hepatic outflow.


Functional MRI of global and local processing in children.
Functional magnetic resonance imaging was used to examine developmental change in hemispheric biases for globally and locally directed analysis of hierarchical forms. In a previous reaction time (RT) study, which presented hierarchical stimuli to the visual hemifields, children 7 to 14 years of age demonstrated an emerging pattern of hemispheric differences. Initially children analyzed local elements more slowly, without a strongly lateralized advantage for local or global level processing. With age, children's development was marked by a left hemisphere advantage for local level processing that resembled an adult's and a trend toward a right hemisphere advantage for global. In the current study, 20 children 12 to 14 years old were imaged during attend-global and attend-local conditions to determine whether the developmental change in cognitive measures corresponded to a change in distribution of functional activation. Children formed two groups based on their RT performance, immature-bilateral (IB) or mature-lateralized (ML). The volume of task-related activation within lateral temporo-occipital regions of interest was compared for global and local conditions between the two groups. The IB children showed greater activation overall for local level processing, comparable activation across the two hemispheres for the global condition, and a trend of right greater than left hemisphere activation for local. In contrast, the ML children displayed right greater than left hemisphere activation during global analysis and the opposite during local processing. Importantly these patterns of functional activation mirror the profiles of RT performance. Together they demonstrate a shift from undifferentiated, bilateral processing toward hemispheric lateralization.


Astaxanthin Protecting Membrane Integrity against Photosensitized Oxidation through Synergism with Other Carotenoids.
Incorporation of astaxanthin or zeaxanthin in giant unilamellar vesicles (GUVs) of phosphatidylcholine resulted in a longer lag phase than incorporation of β-carotene or lycopene for the onset of budding induced by chlorophyll a photosensitization and quantified by a dimensionless entropy parameter using optical microscopy and digital image heterogeneity analysis. The lowest initial rate of GUV budding after the lag phase was seen for GUVs with astaxanthin as the least reducing carotenoid, while the lowest final level of entropy appeared for those with lycopene or β-carotene as a more reducing carotenoid. The combination of astaxanthin and lycopene gave optimal protection against budding with respect to both a longer lag phase and lower final level of entropy by combining good electron acceptance and good electron donation. Quenching of singlet oxygen by carotenoids close to chlorophyll a in the membrane interior in parallel with scavenging of superoxide radicals by astaxanthin anchored in the surface may explain the synergism between carotenoids involving both type I and type II photosensitization by chlorophyll a.


Automatic flow system titration based on multicommutation for spectrophotometric determination of total acidity in silage extracts.
A multicommutated flow titration procedure is proposed for the spectrophotometric determination of total acidity in silage extracts. The flow network comprises a set of 3-way solenoid valves, computer-controlled to provide facilities to handle the titrand, titrant, and carrier solutions by using a single pumping channel. The procedure is based on the volumetric fraction variation approach that maintains the same volume of titrand solution and varies the titrant solution step by step, to provide determination without the use of an analytical curve. The procedure is implemented by using phenolphthalein as an external indicator; the proposed algorithm was able to titrate silage extracts presenting different color intensities. Sample solutions with concentrations ranging from 10(-3) to 10(-1) mol/L total acidity could be analyzed by using 10(-2) mol/L sodium hydroxide as the titrant solution. Other advantages include a relative standard deviation of <1.0% (n = 4) for a typical silage extract solution containing 26 mmol/L total acidity; an analytical throughput of 16 determinations per hour was also achieved. Accuracy was assessed by processing a set of silage extract solutions and comparing the results with those obtained by using the conventional potentiometric titration procedure. No significant difference at the 95% confidence level was observed.


[Cardiology update in 2016].
In 2016 the European Society of Cardiology (ESC) published new guidelines. These documents update the knowledge in various fields such as atrial fibrillation, heart failure, cardiovascular prevention and dyslipidemia. Of course it is impossible to summarize these guidelines in detail. Nevertheless, we decided to highlight the major modifications, and to emphasize some key points that are especially useful for the primary care physician.


Developmental aspects of spinal locomotor function: insights from using the in vitro mouse spinal cord preparation.
Over the last five years, rapid advances have been made in our understanding of the location, function, and recently, organization of the central pattern generator (CPG) for locomotion. In the mammal, the use of the neonatal rat has largely contributed to these advances. Additionally, the use of the in vitro mouse spinal cord preparation is becoming more common, catalysed in part by the potential for the use of genetic approaches to study locomotor function. Although tempting, it is necessary to resist the a priori assumption that the organization of the spinal CPG is identical in the rat and mouse. This review will describe the development of locomotor-like behaviour in the mouse from embryonic day 12 to postnatal day 14. While there are still many gaps in our knowledge, compared with the rat, the in vitro mouse appears to follow a qualitatively similar course of locomotor development. The emphasis in this review is the use or potential use of the mouse as a complement to existing data using the neonatal rat preparation.


Transcriptome predictors of coral survival and growth in a highly variable environment.
Concern over rapid environmental shifts associated with climate change has led to a search for molecular markers of environmental tolerance. Climate-associated gene expression profiles exist for a number of systems, but have rarely been tied to fitness outcomes, especially in nonmodel organisms. We reciprocally transplanted corals between two backreef locations with more and less variable temperature regimes to disentangle effects of recent and native environment on survival and growth. Coral growth over 12 months was largely determined by local environment. Survival, however, was impacted by native environment; corals from the more variable environment had 22% higher survivorship. By contrast, corals native to the less variable environment had more variable survival. This might represent a "selective sieve" where poor survivors are filtered from the more stressful environment. We also find a potential fitness trade-off-corals with high survival under stressful conditions grew less in the more benign environment. Transcriptome samples taken a year before transplantation were used to examine gene expression patterns that predicted transplant survival and growth. Two separate clusters of coexpressed genes were predictive of survival in the two locations. Genes from these clusters are candidate biomarkers for predicting persistence of corals under future climate change scenarios.


Post-acute (long) COVID-19 quality of life: validation of the German version of (PAC19QoL) instrument.
The aim of our study was to validate a German translation of the post-acute (long) COVID-19 quality of life (PAC-19QoL) instrument among German patients with long COVID-19 syndrome. The PAC-19QoL instrument was translated into the German language and administrated to patients with long COVID-19 syndrome. Cronbach's alpha coefficient was used to analyze the internal consistency of the instrument. Construction validity was evaluated by using Pearson's correlation coefficient and Spearman's rank correlation. Scores of patients and controls were compared using the Mann-Whitney U-test. A total of 45 asymptomatic and 41 symptomatic participants were included. In total, 41 patients with long COVID-19 syndrome completed the PAC-19QoL and EQ-5D-5L questionnaires. PAC-19QoL domain scores were significantly different between symptomatic and asymptomatic participants. All items achieved a Cronbach's alpha >0.7. There was a significant correlation between all domains on the test (p < 0.001), with the highest correlation between total (r = 0.994) and domain 1 (r = 0.991). Spearman's rank correlation analysis confirmed that the instrument items correlated with the objective PAC-19QoL examination findings. The German version of the instrument is valid and reliable and can be a suitable tool for research and daily clinical practice among patients with long COVID-19 syndrome.


Effects of food-based enrichment on enclosure use and behavioral patterns in captive mammalian predators: a case study from an Austrian wildlife park.
Combining naturalistic enclosure design and animal welfare with visitor interests and education can be challenging for zoos and wildlife parks. To accomplish both purposes, different types of enrichment (food-based or non-food-based items, such as environmental, sensory, cognitive, social) can be used. The aim of the present study is to investigate the effect of food-based and olfactory enrichments on enclosure use, behavior, and visibility of captive brown bears (Ursus arctos), pine martens (Martes martes), domestic ferrets (Mustela putorius furo), and golden jackals (Canis aureus). We used observational approaches to measure enclosure use, behavior, and visibility during three different experimental phases: (1) pre-enrichment (baseline, no experience with the enrichment yet), (2) during enrichment (enrichment was provided at low frequented locations in the enclosures that are easily visible to visitors), and (3) post-enrichment (enrichment was removed from the enclosures). We found that enrichment led to a uniform use of the enclosure and enhanced visibility in brown bears, increased activity budgets in pine martens, and observed high object interaction in both species. No effects of enrichment were detected in domestic ferrets. Golden jackals did not leave their burrows during daytime during the entire observation period; thus, observations were not possible at all. Our results suggest different effects of food-based enrichment, e.g., enclosure use, temporal activity patterns, and animal visibility. However, further studies should control for the specific role of the factors involved. Our study represents one of the first explorations of food-based enrichment in rather understudied species.


Nanoshell Assembly for Magnet-Responsive Oil-Degrading Bacteria.
The modified polyelectrolyte-magnetite nanocoating was applied to functionalize the cell walls of oil decomposing bacteria Alcanivorax borkumensis. Cationic coacervate of poly(allylamine) and 20 nm iron oxide nanoparticles allowed for a rapid single-step encapsulation process exploiting electrostatic interaction with bacteria surfaces. The bacteria were covered with rough 70-100-nm-thick shells of magnetite loosely bound to the surface through polycations. This encapsulation allowed for external manipulations of A. borkumensis with magnetic field, as demonstrated by magnetically facilitated cell displacement on the agar substrate. Magnetic coating was naturally removed after multiple cell proliferations providing next generations of the cell in the native nonmagnetic form. The discharged biosurfactant vesicles indicating the bacterial functionality (150 ± 50 nm lipid micelles) were visualized with atomic force microscopy in the bacterial biofilms.


The Constituent Phases and Micromechanical Properties of Steel Corrosion Layers Generated by Hyperbaric-Oxygen Accelerated Corrosion Test.
Hyperbaric oxygen-accelerated corrosion testing (HOACT) is a newly developed method to study in the labor the corrosion behavior of steel bars in concrete. This work aimed to intensively investigate the mechanical properties and microstructures of HOACT-generated corrosion products by means of nano-indentation tests, Raman micro-spectrometry, and scanning electron microscopy. The local elastic modulus and nanohardness varied over wide ranges of 6.8-75.2 GPa and 0.38-4.44 GPa, respectively. Goethite, lepidocrocite, maghemite, magnetite, and akageneite phases were identified in the corrosion products. Most regions of the rust layer were composed of a complex and heterogeneous mix of different phases, while some regions were composed of maghemite or akageneite only. The relationship between the micromechanical properties and typical microstructural features is finally discussed at the micro-scale level. It was found that the porosity of corrosion products can significantly influence their micromechanical properties.


Plasma and erythrocyte kinetic considerations in lithium therapy.
Developments in the analysis and pharmacokinetics of lithium, and the role of the pharmacist in the management of lithium therapy in affective disorders, are described. Research showing that lithium levels in the brain may be better predicted from erythrocyte lithium levels than plasma levels is reviewed. Also reviewed is lithium kinetics in affective disorders. The pharmacist (1) determines relevant aspects of the patient's condition, (2) develops an appropriate blood sampling schedule, (3) initiates and maintains a serial lithium erythrocyte and plasma patient profile, (4) evaluates erythrocyte and serum levels in relation to established criteria to provide a basis for differential diagnosis of the patient, and (5) individualizes lithium dosage and schedules. Four cases are used to illustrate this approach. It is suggested that outpatient mental health clinics would be likely settings for the further development of this clinical role.


Invasive Breast Cancer: miR-24-2 Targets Genes Associated with Survival and Sensitizes MDA-MB-231 Cells to Berberine.
MicroRNA aberrations including that of miR-24-2 have been reported in various cancers. However, the target genes for miR-24-2 are yet to be identified and validated in invasive breast cancer and the triple-negative breast cancer (TNBC). Using in silico approaches and gene expression analyses, we identified and validated the target genes of miR-24-2 in invasive breast cancer, majority of which were TNBC. We studied the translational potential of these target genes using berberine in a TNBC cell line. Differentially expressed genes targeted by miR-24-2 were identified and analyzed for their survival effects using the The Cancer Genome Atlas-Breast Invasive Carcinoma (-BRCA) samples. Furthermore, we carried out protein-protein interaction, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene expression, and Kaplan-Meier survival analyses using common targets of miR-24-2 in invasive breast cancer/TNBC. We identified 11 biomarker candidate genes as crucial targets of miR-24-2. The survival of breast cancer patients was significantly associated with the low expressions of nine genes, including RACGAP1, KIAA1199, TIMM17A, LYRM7, IL1R1, SLC1A3, DTX4, L1CAM, and SAP30-like (SAP30L), and high expressions of two genes, SOD2 and HLA-DQB2. These in silico findings were validated by overexpressing miR-24-2 and assessing the expression pattern of these target genes in the TNBC MDA-MB-231 cells. miR-24-2 overexpression inhibited (by 20%; p < 0.001) cell proliferation and sensitized the anticancer effect of berberine. In all, this study reports on the novel target genes of miR-24-2 in invasive breast cancer/TNBC, and that miR-24-2 sensitizes MDA-MB-231 cells to berberine. These data lend evidence for the translational potentials of miR-24-2 for invasive breast cancer diagnostic and therapeutic innovation.


Human toxocariasis: a seroepidemiological survey in schoolchildren of Sorocaba, Brazil.
A seroepidemiological survey for toxocariasis, among 180 schoolchildren of the public schools of Sorocaba City, state of São Paulo, Brazil, was carried out from August 2000 to July 2001. ELISA test was performed using excretory and secretory antigens for the detection of IgG anti-Toxocara antibodies. Information regarding the children was obtained from the parents or legal guardians. The results showed that the mean age was 5.4 +/- 1.4 years, the infection coefficient (IC) was 38.3 and the infection risk was higher among the children living in the city outskirts (IC = 47.4) where the socioeconomic conditions were worse than in the central region of the city (IC = 11.1). There was an association between higher frequency of seroreactivity in the ELISA test and the condition of living in a house with a yard and/or unpaved street. The same was observed in relation to a history of enteroparasitism. There was also an association between a seronegative ELISA test and previous treatment of pet dogs and/or cats with vermifuge. Based on these results, the authors propose that public health programs should include anthelmintic for dogs and cats during the antirabies vaccination campaigns, in order to diminish environmental contamination with Toxocara spp. eggs and consequently human infection.


An Invertebrate Burn Wound Model That Recapitulates the Hallmarks of Burn Trauma and Infection Seen in Mammalian Models.
The primary reason for skin graft failure and the mortality of burn wound patients, particularly those in burn intensive care centers, is bacterial infection. Several animal models exist to study burn wound pathogens. The most commonly used model is the mouse, which can be used to study virulence determinants and pathogenicity of a wide range of clinically relevant burn wound pathogens. However, animal models of burn wound pathogenicity are governed by strict ethical guidelines and hindered by high levels of animal suffering and the high level of training that is required to achieve consistent reproducible results. In this study, we describe for the first time an invertebrate model of burn trauma and concomitant wound infection. We demonstrate that this model recapitulates many of the hallmarks of burn trauma and wound infection seen in mammalian models and in human patients. We outline how this model can be used to discriminate between high and low pathogenicity strains of two of the most common burn wound colonizers Pseudomonas aeruginosa and Staphylococcus aureus, and multi-drug resistant Acinetobacter baumannii. This model is less ethically challenging than traditional vertebrate burn wound models and has the capacity to enable experiments such as high throughput screening of both anti-infective compounds and genetic mutant libraries.


Serum levels of 20 kilodalton human growth hormone (20K-hGH) in patients with acromegaly before and after treatment with octreotide and transsphenoidal surgery.
Circulating human GH (hGH) consists of several molecular isoforms. It was previously reported that the proportion of 20 kilodalton hGH (20K-hGH) was elevated in the serum of patients with active acromegaly. In this study, we investigated the effects of octreotide and transsphenoidal adenomectomy on the proportion of 20K-hGH in the serum of 7 acromegalic patients. To achieve an acute effect, octreotide (100 microg) was subcutaneously injected as a bolus. To observe the chronic effects of octreotide therapy and surgery, serum samples were obtained by repetitive blood sampling before and 3 to 8 weeks after treatment. Serum levels of 20K-hGH and 22 kilodalton hGH (22K-hGH) were determined by specific enzyme-linked immunosorbent assay. A bolus injection of octreotide elicited a parallel decrease in serum 22K-hGH and 20K-hGH, resulting in an unchanged proportion of 20K-hGH to total circulating hGH. The proportion of 20K-hGH was decreased in 4 of 4 patients 4 to 7 weeks after surgery and in 2 of 4 patients after chronic treatment with octreotide for 3 to 8 weeks. The proportion of serum 20K-hGH was positively related to mean serum 20K-hGH as well as serum total hGH levels, but not with serum IGF-I levels. These findings suggest that high serum levels of 20K-hGH or total hGH per se might elicit a chronic change in the clearance kinetics of 20K-hGH and increase the proportion of 20K-hGH in acromegalic patients.


Partial and complete microdeletions of Y chromosome in infertile males from South of Iran.
Y chromosome microdeletions are the second genetic cause of male infertility. The incidence of Y chromosome microdeletions can vary considerably depending on several factors, including patient selection criteria, population composition, and diagnostic protocols. They are associated with spermatogenic failure and lead to azoospermia or oligozoospermia. The advance in assisted reproductive technology and intracytoplasmic sperm injection, and the possibility of genetic defect transmission to the next generation make it necessary to improve our knowledge about the various factors leading to spermatogenic impairment. This study was designed to determine the frequency of microdeletions of Y chromosome in a population from South of Iran. 81 infertile males with non-obstructive azoospermia or oligozoospermia were selected. Multiplex PCR using several STS markers was carried out to detect the complete or partial microdeletions. The frequency of both complete and partial microdeletions in men with azoospermia or severe oligozoospermia was 7.4%. All microdeletions were observed in AZFc region. There was 1.25% complete microdeletions and after excluding complete microdeletions, we detected 5% gr/gr and 1.25% b2/b3 microdeletions. In our control group of fertile males, 4% gr/gr microdeletions was detected while there was no b2/b3 microdeletions. We concluded that there is a low frequency of Y chromosome microdeletions in a population of infertile males from South of Iran. b2/b3 microdeletions was detected only in infertile males and not in the control group. Screening a population with larger sample size is necessary to determine the involvement of this partial microdeletion in infertility of this population.